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Sample records for carbamazepine

  1. Carbamazepine

    Science.gov (United States)

    ... Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in ... older (about 1 in 500 people) who took anticonvulsants such as carbamazepine to treat various conditions during ...

  2. Nail changes after carbamazepine

    Directory of Open Access Journals (Sweden)

    Chopra Adarsh

    2000-01-01

    Full Text Available Antiepileptics are known to produce different types of side effects including nail changes. A 20-year-old epileptic man had yellowish discolouration followed by dystrophy and onycholysis of his 15 nails after taking carbamazepine for 3 months which cleared within six months after discontinuation of the drug. This type of change has not been reported earlier with carbamazepine

  3. Carbamazepine-Induced Diarrhea

    OpenAIRE

    J Gordon Millichap

    1992-01-01

    Intractable diarrhea induced by carbamazepine (CBZ) in 3 patients and necessitating discontinuation of the drug is reported from the Departments of Neurology and Medicine, University of Louisville School of Medicine, Kentucky.

  4. Non-recurrence of carbamazepine induced vitiligo after rechallenge with carbamazepine.

    Directory of Open Access Journals (Sweden)

    Masoomeh Saeedloo

    2013-12-01

    Full Text Available Vitiligo is a rare side effect of carbamazepine whose exact mechanism is unknown. The aim of this report is to describe a single case of vitiligo induced by carbamazepine.The case was a patient with Bipolar I disorder whose medications were changed from valproate to carbamazepine and who developed vitiligo after a short while. We followed the case for about four years when he was rechallenged with carbamazepine.When depigmentation occurred, we immediately discontinued carbamazepine after which the depigmented areas improved gradually. About three years later, he received carbamazepine again, but depigmentation did not recur.Carbamazepine-induced vitiligo is not an absolute contraindication for the prescription of carbamazepine if other choices fail to respond or are not tolerated. The case has implications for the mechanism of medication induced vitiligo.

  5. Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.

    2009-01-01

    Background Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. Objectives To compare efficacy and tolerability of carbamazepine and oxcarbazepine mono

  6. Extracorporeal treatment for carbamazepine poisoning

    DEFF Research Database (Denmark)

    Ghannoum, Marc; Yates, Christopher; Galvao, Tais F

    2014-01-01

    CONTEXT: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. OBJECTIVES: To perform a systematic review and provide clinical recommendations for ECTR...... Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. RESULTS: Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in......-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR...

  7. Compound list: carbamazepine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available carbamazepine CBZ 00018 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/car...bamazepine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/car...bamazepine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/car...edbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/carbamazepine.Rat.in_vivo.Liver.Repeat.zip ...

  8. Carbamazepine degradation by photolysis and titanium dioxide photocatalysis.

    Science.gov (United States)

    Im, Jong-Kwon; Son, Hyun-Seok; Kang, Young-Min; Zoh, Kyung-Duk

    2012-07-01

    We investigated the degradation of carbamazepine by photolysis/ultraviolet (UV)-C only and titanium dioxide photocatalysis. The degradation of carbamazepine by UV-only and titanium-dioxide-only (adsorption) reactions were inefficient, however, complete degradation of carbamazepine was observed by titanium dioxide photocatalysis within 30 min. The rate of degradation increased as initial carbamazepine concentration decreased, and the removal kinetics fit well with the Langmuir-Hinshelwood model. The addition of methanol, a radical scavenger, decreased carbamazepine removal, suggesting that the hydroxide radical played an important role during carbamazepine degradation. The addition of oxygen during titanium dioxide photocatalysis accelerated hydroxide radical production, thus improving mineralization activity. The photocatalytic degradation was more efficient at a higher pH, whereas the removal of carbamazepine and acridine (a major intermediate) were more efficient under aerobic conditions. The mineralization of carbamazepine during photocatalysis produced various ionic by-products such as ammonium and nitrate by way of nitrogen dioxide.

  9. Acetaminophen toxicity with concomitant use of carbamazepine.

    Science.gov (United States)

    Jickling, Glen; Heino, Angela; Ahmed, S Nizam

    2009-12-01

    Acetaminophen is a widely used analgesic that can cause acute liver failure when consumed above a maximum daily dose. Certain patients may be at increased risk of hepatocellular damage even at conventional therapeutic doses. We report a case of a 34-year-old man on carbamazepine for complex partial seizures who developed acute liver and renal failure on less than 2.5 grams a day of acetaminophen. This raises caution that patients on carbamazepine should avoid chronic use of acetaminophen, and if required use at lower doses with vigilant monitoring for signs of liver damage.

  10. Anticonvulsant hypersensitivity syndrome secondary to carbamazepine

    Science.gov (United States)

    Brown, Shannon C.

    2017-01-01

    Anticonvulsant hypersensitivity syndrome (AHS) is a potentially fatal multiorgan drug reaction that presents with various cutaneous eruptions. There is a genetic predisposition to such reactions. We present a young woman with AHS due to carbamazepine that presented as an atypical erythema multiforme with elevated liver enzymes. PMID:28127149

  11. Fate of Carbamazepine during Water Treatment

    DEFF Research Database (Denmark)

    Kosjek, T.; Andersen, Henrik Rasmus; Kompare, Boris;

    2009-01-01

    Seven transformation products of carbamazepine generated by at least one of three common water treatment technologies (W-radiation, oxidation with chlorine dioxide (ClO2), and biological treatment with activated Sludge) were identified by complementary use of ion trap, single quadrupole...

  12. NQR frequencies of anhydrous carbamazepine polymorphic phases

    CERN Document Server

    Bonin, C J; Pusiol, D J

    2010-01-01

    In this work we propose the Nuclear Quadrupole Resonance (NQR) technique as an analytical method suitable for polymorphism detection in active parts (or active principles) of pharmaceuticals with high pharmacological risk. Samples of powder carbamazepine (5H-dibenz(b,f)-azepine-5-carboxamide) are studied. In its anhydrous state, this compound presents at least three different polymorphic forms: form III, the commercial one, form II, and form I. Of these, only form III possesses desirable therapeutic effects. By using the NQR technique, it was possible to characterize two of the three polymorphic phases (I and III) for anhydrous carbamazepine in few minutes at room temperature, detecting the characteristic frequencies of 14N nuclei (I=1) present in their chemical composition and in the frequency range 2.820-3.935 MHz. For form II, characteristic lines were not detected within this range of frequencies. The lines detected for form III are centered at the frequencies \

  13. [Extended hemoperfusion in the treatment of acute carbamazepine intoxication].

    Science.gov (United States)

    Peces, R; Azorín, S; Peces, C; Selgas, R

    2010-01-01

    Carbamazepine is used in the treatment of epilepsy, and also prescribed in neuralgic pain syndromes, and certain affective disorders. Carbamazepine intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, arrhythmia, hemodynamic instability and death. The drug's relatively high molecular weight, elevated volume of distribution and intense protein-binding render it difficult to extracorporeal removal, but published experience with hemoperfusion or hemodialysis present variable results. We describe a case report involving carbamazepine intoxication who was successfully treated with charcoal hemoperfusion. With this treatment the half-life of carbamazepine was reduced with rapid lowering of carbamazepine levels and clinical improvement. Based on our experience in this patient and a review of previously reported cases, extended charcoal hemoperfusion should be considered for serious carbamazepine intoxication because free as well as bound drug fractions are eliminated via this technique.

  14. Sorption and desorption of carbamazepine from water by smectite clays.

    Science.gov (United States)

    Zhang, Weihao; Ding, Yunjie; Boyd, Stephen A; Teppen, Brian J; Li, Hui

    2010-11-01

    Carbamazepine is a prescription anticonvulsant and mood stabilizing pharmaceutical administered to humans. Carbamazepine is persistent in the environment and frequently detected in water systems. In this study, sorption and desorption of carbamazepine from water was measured for smectite clays with the surface negative charges compensated with K+, Ca2+, NH4+, tetramethylammonium (TMA), trimethylphenylammonium (TMPA) and hexadecyltrimethylammonium (HDTMA) cations. The magnitude of sorption followed the order: TMPA-smectite≥HDTMA-smectite>NH4-smectite>K-smectite>Ca-smectite⩾TMA-smectite. The greatest sorption of carbamazepine by TMPA-smectite is attributed to the interaction of conjugate aromatic moiety in carbamazepine with the phenyl ring in TMPA through π-π interaction. Partitioning process is the primary mechanism for carbamazepine uptake by HDTMA-smectite. For NH4-smectite the urea moiety in carbamazepine interacts with exchanged cation NH4+ by H-bonding hence demonstrating relatively higher adsorption. Sorption by K-, Ca- and TMA-smectites from water occurs on aluminosilicate mineral surfaces. These results implicate that carbamazepine sorption by soils occurs primarily in soil organic matter, and soil mineral fractions play a secondary role. Desorption of carbamazepine from the sorbents manifested an apparent hysteresis. Increasing irreversibility of desorption vs. sorption was observed for K-, Ca-, TMA-, TMPA- and HDTMA-clays as aqueous carbamazepine concentrations increased. Desorption hysteresis of carbamazepine from K-, Ca-, NH4-smectites was greater than that from TMPA- and HDTMA-clays, suggesting that the sequestrated carbamazepine molecules in smectite interlayers are more resistant to desorption compared to those sorbed by organic phases in smectite clays.

  15. A comparison of carbamazepine Divitabs and a normal carbamazepine preparation in psychiatric and oligophrenic patients

    NARCIS (Netherlands)

    Nijdam, J.R.; Doorschot, C.H.; Van Bavel, L.P.; Loonen, A.J.M.

    1992-01-01

    Twenty patients who had become accustomed to a stable oral carbamazepine dose participated in an open, randomized, two-centre, cross-over study, in which ordinary tablets and Divitabs (a new sustained release preparation) were compared. Pharmacokinetic parameters, seizure control, effects on the beh

  16. Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain.

    Science.gov (United States)

    Ren, Zhenyu; Yang, Bing; Yang, Bin; Shi, Le; Sun, Qing-Li; Sun, A-Ping; Lu, Lin; Liu, Xiaoguang; Zhao, Rongsheng; Zhai, Suodi

    2015-11-01

    Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient's pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient's pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioid-induced hyperalgesia in chronic neuropathic pain patients.

  17. Ecotoxicity of carbamazepine and its UV photolysis transformation products

    DEFF Research Database (Denmark)

    Donner, E.; Kosjek, T.; Qualmann, Signe

    2013-01-01

    ecotoxicity assays (representing bacteria, algae and crustaceans). UV-treatment of 6 mg L− 1 carbamazepine solution was carried out over a 120 min period and samples were removed periodically over the course of the experiment. Quantification results confirmed the degradation of carbamazepine throughout...... were still inhibited > 60% relative to control populations upon dosing with 90 + min UV-treated carbamazepine solution. Single compound toxicity testing also confirmed the higher toxicity of measured degradation products relative to the parent compound. These results show that transformation products...... considerably more toxic than carbamazepine itself may be produced during UV-treatment of wastewater effluents and/or photo-induced degradation of carbamazepine in natural waters. This study highlights the need to consider mixture toxicity and the formation and persistence of toxicologically relevant...

  18. Musical hallucinations responding to a further increase of carbamazepine.

    Science.gov (United States)

    Aizawa, Saeko; Terao, Takeshi; Hatano, Koji; Ishii, Nobuyoshi

    2014-09-24

    A 73-year-old woman outpatient with mild cognitive impairment, parasomnia and depressive state with musical hallucinations failed to respond to 400 mg/day of valproate. Once she was admitted to a university hospital, her musical hallucinations partially responded to 1 mg/day of clonazepam and sufficiently improved on 100 mg/day of carbamazepine. Two months after discharge, however, her musical hallucinations recurred probably as a consequence of psychological stress. The increase of carbamazepine from 100 to 200 mg/day completely remitted her musical hallucinations. This case suggests that musical hallucinations respond in a dose-dependent manner to increasing carbamazepine, and that gradual titration from small doses of carbamazepine is required because optimal doses appear to be smaller than those required for epilepsy and bipolar disorder. Further studies are warranted to determine the therapeutic levels of carbamazepine for musical hallucinations.

  19. Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin.

    Science.gov (United States)

    Medarević, Djordje; Kachrimanis, Kyriakos; Djurić, Zorica; Ibrić, Svetlana

    2015-10-12

    In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus® and two types of hydroxypropyl methylcellulose-Metolose® 90SH-100 and Metolose® 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-Soluplus® systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.

  20. Cognitive and Behavioral Effects of Topiramate Versus Carbamazepine Monotherapy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-09-01

    Full Text Available The cognitive and behavioral effects of topiramate (TPM versus carbamazepine (CBZ were evaluated in a multicenter, randomized, open-label, parallel-group trial at Sanggye Paik Hospital, Seoul, and other university centers in Korea.

  1. Formulation and optimization of carbamazepine floating tablets

    Directory of Open Access Journals (Sweden)

    Patel D

    2007-01-01

    Full Text Available Floating tablets of carbamazepine were developed using melt granulation technique. Bees wax was used as a hydrophobic meltable material. Hydroxypropylmethylcellulose, sodium bicarbonate and ethyl cellulose were used as matrixing agent, gas-generating agent and floating enhancer, respectively. The tablets were evaluated for in vitro buoyancy and dissolution studies. A simplex lattice design was applied to investigate the combined effect of 3 formulation variables i.e. amount of hydroxypropyl methylcellulose ( X 1 , ethyl cellulose ( X 2 and sodium bicarbonate ( X 3 . The floating lag time (F lag , time required for 50% (t 50 and 80% drug dissolution (t 80 were taken as responses. Results of multiple regression analysis indicated that, low level of X 1 and X 2 , and high level of X 3 should be used to manufacture the tablet formulation with desired in vitro floating time and dissolution. Formulations developed using simplex lattice design were fitted to various kinetic models for drug release. Formulation S3 was selected as a promising formulation and was found stable at 40 o and 75% relative humidity for 3 months. Present study demonstrates the use of simplex lattice design in the development of floating tablets with minimum experimentation.

  2. Aggravation of symptomatic occipital epilepsy of childhood by carbamazepine

    Directory of Open Access Journals (Sweden)

    Škrijelj Fadil E.

    2014-01-01

    Full Text Available Introduction. Carbamazepine can lead to aggravation of epileptic seizures in generalized epilepsies (primary or secondary with clinical manifestations of absence (typical or atypical and/or myoclonic seizures. However, some focal epilepsies can be also aggravated by the introduction of carbamazepine. Case report. We presented a 10-year-old boy born after a complicated and prolonged delivery completed by vacuum extraction, of early psychomotor development within normal limits. At the age of 8 years he had the first epileptic seizure of simple occipital type with generalization and urination. Brain magnetic resonance imaging (MRI showed focal cortical reductions in the left parietal and occipital regions. Interictal EEG recorded slowed basic activities above the posterior regions of the left hemisphere, with intermittent occurrence of occipital sharp waves and bioccipital sharp and slow-wave complexes. Initially, treatment with valproate was administered; however, the addition of carbamazepine into therapy induced aggravation of seizures and EEG findings, changed behavior and poor performance at school. By withdrawal of carbamazepine the condition improved both clinically and in EEG findings. Conclusion. Childhood occipital epilepsy lesions show deterioration due to carbamazepine, which if administered induces aggravation of seizures, behavior changes, cognition with occurrence of long-term bilateral discharges, and posterior sharp and slow wave high amplitude complexes recorded by EEG.

  3. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

    Directory of Open Access Journals (Sweden)

    Parthasarathy Govindasamy

    2013-12-01

    Conclusions: The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine.

  4. Neuroleptic Malignant Syndrome Caused by a Combination of Carbamazepine and Amitriptyline

    Directory of Open Access Journals (Sweden)

    A. Bruce Janati

    2012-01-01

    Full Text Available A 32-year-old female, with a history of secondarily-generalized convulsive epilepsy, mental retardation, and a psychiatric illness, developed neuroleptic malignant syndrome while receiving carbamazepine and amitriptyline concurrently. We hypothesize that the addition of amitriptyline to carbamazepine caused a decrease in the serum level of carbamazepine, resulting in NMS. We conclude that combination therapy with carbamazepine and amitriptyline should be avoided in patients who are predisposed to NMS. The purpose of this paper is to warn physicians against combination therapy with carbamazepine and tricyclic antidepressants which may be conducive to neuroleptic malignant syndrome in susceptible patients.

  5. Optimization and validation of bioanalytical SPE – HPLC method for the simultaneous determination of carbamazepine and its main metabolite, carbamazepine-10, 11-epoxide, in plasma

    Directory of Open Access Journals (Sweden)

    Jasmina Tonic – Ribarska

    2012-03-01

    Full Text Available Carbamazepine is widely used as an antiepileptic drug in the treatment of partial and generalized tonic-clonic seizures. Carbamazepine 10,11-epoxide is the most important metabolite of carbamazepine, because it is a pharmacologically active compound with anticonvulsant properties. According to that, the routine analysis of carbamazepine 10,11-epoxide along with carbamazepine may provide optimal therapeutic monitoring of carbamazepine treatment. The aim of this study was to optimize and validate a simple and reliable solid - phase extraction method followed by RP-HPLC for the simultaneous determination of plasma levels of carbamazepine and carbamazepine-10,11-epoxide, in order to assure the implementation of the method for therapeutic monitoring. The extraction of the analytes from the plasma samples was performed by means of a solid-phase extraction procedure. The separation was carried out on a reversed-phase column using isocratic elution with acetonitrile and water (35:65, v/v as a mobile phase. The temperature was 30°C and UV detection was set at 220 nm. The extraction yield values were more than 98% for all analytes, measured at four concentration levels of the linear concentration range. The method displayed excellent selectivity, sensitivity, linearity, precision and accuracy. Stability studies indicate that stock solutions and plasma samples were stabile under different storage conditions at least during the observed period. The method was successfully applied to determine the carbamazepine and carbamazepine-10,11-epoxide in plasma of epileptic patients treated with carbamazepine as monotherapy and in polytherapy. In conclusion, the proposed method is suitable for application in therapeutic drug monitoring of epileptic patients undergoing treatment with carbamazepine.

  6. Carbamazepine-Induced Hyponatremia in Patients with Mental Retardation.

    Science.gov (United States)

    Kastner, Ted; And Others

    1992-01-01

    This study of 40 patients with mental retardation receiving carbamazepine found hyponatremia in only 5 percent of these patients and found a statistically, but not clinically, significant decrease in serum sodium levels in patients receiving anticonvulsant polytherapy. Results support the use of this drug with patients with mental retardation and…

  7. Use of carbamazepine in psychosis after neuroleptic malignant syndrome.

    Science.gov (United States)

    Peet, M; Collier, J

    1990-04-01

    A case is described of NMS during treatment with sulpiride. The subsequent psychosis resolved during treatment with carbamazepine. It is proposed that this patient may have suffered from a supersensitivity psychosis, and that resolution of her post-NMS psychosis could have been spontaneous.

  8. In vitro evaluation of carbamazepine 200 mg tablets.

    Science.gov (United States)

    Kibwage, I O; Nguyo, M

    1993-08-01

    A comparative in-vitro performance of carbamazepine 200mg tablet products available on the Kenyan market was evaluated. The products which include the innovator product, Tegretol, have similar quality consonant with pharmacopoeial specifications. A batch of one of the products had a carbamazepine content of 106.6% label claim which was outside the upper limits of 105%. One product packaged in multiple-unit containers of a 1000, had an unacceptable high friability of 6.82% loss in weight. All products had good dissolution profiles and released at least 70% of the dose within 45 minutes. Drug dissolution from tablets was found to vary between batches for one product. At each sampling time, most generics had wide variations in amount of dissolved drug. The effect of such variations on tablet efficacy cannot be ascertained in the absence of bioavailability data.

  9. Charcoal Hemoperfusion vs. High Efficiency Hemodialysis in Carbamazepine Intoxication: A Case Report

    Directory of Open Access Journals (Sweden)

    Arzu KAHVECİ

    2011-05-01

    Full Text Available Carbamazapine is a commonly used antiepileptic agent. Neurological abnormalities which can progress to coma, arrhythmias, respiratory depression and eye abnormalities such as nystagmus are seen in an intoxication setting. There is no specific antidote for the treatment of carbamazepine intoxication and supportive therapy is generally recommended. Carbamazepine is not removed through conventional hemodialysis as it highly bound to proteins. Charcoal hemoperfusion has been reported as the standard effective treatment method. Herein we report a 23-year-old woman with high dose carbamazepine overdose treated with high efficiency hemodialysis and charcoal hemoperfusion. We also discuss a comparison of the methods used for carbamazepine intoxication.

  10. Improvement of physicomechanical properties of carbamazepine by recrystallization at different pH values.

    Science.gov (United States)

    Javadzadeh, Yousef; Mohammadi, Ameneh; Khoei, Nazaninossadat Seyed; Nokhodchi, Ali

    2009-06-01

    The morphology of crystals has an appreciable impact role on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviours of drugs. The objective of this study was to achieve an improved physicomechanical property of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution rate was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressure and measuring their hardness. SEM studies showed that the carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle shape. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature during recrystallization procedure or pH of crystallization media. The crushing strength of tablets indicated that all of the recrystallized carbamazepine samples had better compactiblity than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate for carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.

  11. Erythema multiforme as the result of taking carbamazepine

    Directory of Open Access Journals (Sweden)

    Maharani Laillyza Apriasari

    2010-06-01

    Full Text Available Background: Erythema multiforme is an acute mucocutaneus disease which is caused by the hypersensitivity reaction. It is characterized by target lesions on the skin or ulcerative oral lesion. Etiology of the disease is unknown, it is currently considered as immunologic disease. The triggering factors is the use of certain type of drugs like antibiotics, anticonvulsant, and NSAID. Most of the dentists do not know about it is mechanism, so a lot of people consider it as a malpractice. Purpose: This paper reported a case of a man, 46 years old which had ulcerative oral mucous, peeled and pain lips after taking carbamazepine drugs. Case: The clinical diagnosis of this case was erythema multiforme because of the hypersensitivity reaction as the result of taking carbamazepine. Case management: The final diagnosis based on anamnesis history of taking systemic drugs and clinical manifestation of erythema multiforme in the oral cavity. The drugs therapy that had been given were antihistamine, oral corticosteroid, gargle liquid contained of topical anesthetic, corticosteroid, and antibiotic. Conclusion: In this case, it can be concluded that erythema multiforme appeared was triggered by taking carbamazepine as the drug of choice for trigeminal neuralgia therapy. These drugs can cause type III hypersensitivity reaction. The final diagnosis based on anamnesis history of taking carbamazepine before lesions erupted and the characterized clinical manifestation.Latar belakang: Erythema multiforme adalah penyakit mukokutaneus akut yang menyerang kulit dan mukosa sebagai akibat dari reaksi hipersensitivitas. Secara karakteristik ditandai oleh lesi target pada kulit atau lesi ulserasi pada mukosa rongga mulut. Etiologi penyakit ini belum jelas, diduga karena adanya reaksi imunologi. Pencetusnya dikarenakan adanya pemakaian obat-obatan tertentu seperti antibiotik, antikonvulsan dan NSAID. Banyak dokter gigi kurang memahami mekanisme timbulnya penyakit ini, sehingga

  12. Stevens-Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2011-01-01

    Full Text Available Carbamazepine and other anticonvulsants are commoner cause of severe adverse cutaneous drug reactions such as erythema multiforme, toxic epidermal necrolysis (TEN, and Stevens-Johnson syndrome (SJS. We report a case of SJS rapidly progressing to TEN with a combination of haloperidol and carbamazepine in a patient with bipolar affective disorder. The pathophysiological mechanism underlying this reaction is discussed.

  13. Life-history consequences for Daphnia pulex exposed to pharmaceutical carbamazepine

    NARCIS (Netherlands)

    Lürling, M.F.L.L.W.; Sargant, E.M.; Roessink, I.

    2006-01-01

    The effects of the antiepileptic, analgesic drug carbamazepine on the growth, morphology, and life-history characteristics of Daphnia pulex were examined at nominal concentrations of 0, 0.1, 1, 10, 100, and 200 mu g L-1. At 1 mu g carbamazepine L-1, Daphnia matured and reproduced slightly earlier th

  14. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2011-03-24

    Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) in the Han Chinese and other Asian populations but not in European populations.

  15. Transformation Pathways of the Recalcitrant Pharmaceutical Compound Carbamazepine by the White-Rot Fungus Pleurotus ostreatus: Effects of Growth Conditions.

    Science.gov (United States)

    Golan-Rozen, Naama; Seiwert, Bettina; Riemenschneider, Christina; Reemtsma, Thorsten; Chefetz, Benny; Hadar, Yitzhak

    2015-10-20

    The widely used anticonvulsant pharmaceutical carbamazepine is recalcitrant in many environmental niches and thus poses a challenge in wastewater treatment. We followed the decomposition of carbamazepine by the white-rot fungus Pleurotus ostreatus in liquid culture compared to solid-state fermentation on lignocellulosic substrate where different enzymatic systems are active. Carbamazepine metabolites were identified using liquid chromatography-high-resolution mass spectrometry (LC-Q-TOF-MS). In liquid culture, carbamazepine was only transformed to 10,11-epoxy carbamazepine and 10,11-dihydroxy carbamazepine as a dead-end product. During solid-state fermentation, carbamazepine metabolism resulted in the generation of an additional 22 transformation products, some of which are toxic. Under solid-state-fermentation conditions, 10,11-epoxy carbamazepine was further metabolized via acridine and 10,11-dihydroxy carbamazepine pathways. The latter was further metabolized via five subpathways. When (14)C-carbonyl-labeled carbamazepine was used as the substrate, (14)C-CO2 release amounted to 17.4% of the initial radioactivity after 63 days of incubation. The proposed pathways were validated using metabolites (10,11-epoxy carbamazepine, 10,11-dihydroxy carbamazepine, and acridine) as primary substrates and following their fate at different time points. This work highlights the effect of growth conditions on the transformation pathways of xenobiotics. A better understanding of the fate of pollutants during bioremediation treatments is important for establishment of such technologies.

  16. Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

    Science.gov (United States)

    Malhotra, S; Dixit, R K; Garg, S K

    2002-01-01

    The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

  17. Carbamazepine breakthrough as indicator for specific vulnerability of karst springs: application on the Jeita spring, Lebanon

    Science.gov (United States)

    Doummar, J.; Geyer, T.; Noedler, K.; Sauter, M.

    2014-12-01

    The pharmaceutical drug carbamazepine is considered an effective wastewater marker. The varying concentration of this drug was analyzed in a mature karst spring following a precipitation event. The results show that carbamazepine is an indicator of wastewater entering the system through a fast flow pathway, leading to an increase of the drug concentrations in spring water shortly after a strong rainfall event. The analysis of the breakthrough curve of carbamazepine along with the electrical conductivity signal and major ions chemograph allowed the development of a conceptual model for precipitation event-based flow and transport in the investigated karst system. Furthermore the amount of newly recharged water and the mass of carbamazepine reaching the aquifer system during the event could be estimated using a simple mixing approach. The distance between the karst spring and the potential carbamazepine source was estimated by the combination of results from artificial tracer tests and the carbamazepine breakthrough curve. The assessment of spring responses to precipitation event using persistent drugs like carbamazepine helps assess the effect of waste water contamination at a spring and gives therefore insights to the specific vulnerability of a karst spring.

  18. Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

    Directory of Open Access Journals (Sweden)

    Massimo Calderazzo

    2015-06-01

    Full Text Available We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6. The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml.

  19. Electrochemical degradation of carbamazepine using modified electrode with graphene-AuAg composite

    Science.gov (United States)

    Pogacean, F.; Biris, A. R.; Socaci, C.; Floare-Avram, V.; Rosu, M. C.; Coros, M.; Pruneanu, S.

    2015-12-01

    Carbamazepine is a pharmaceutical drug which has been detected in surface and drinking water primarily due to human usage but also from the accidental disposal of pharmaceuticals into sewers. We have developed a graphene-modified electrode which was tested at the detection and degradation of carbamazepine. The oxidation process was studied by cyclic voltammetry in aqueous and organic solutions. The electrochemical degradation of carbamazepine was performed by polarizing the working electrode at a certain potential, for different times (from 5 to 60 minutes). The degradation efficiency was highly dependent on the type of solution and on the supporting electrolyte.

  20. Carbamazepine-induced Stevens Johnson syndrome: a case series of three case reports

    Directory of Open Access Journals (Sweden)

    Arvind Kumar

    2015-08-01

    Full Text Available Carbamazepine is an iminostilbene derivative that was initially used as an antiepileptic but has been used with increased frequency for different indications including chronic pain, trigeminal neuralgia, and herpetic neuralgias. This has resulted in increased incidence of carbamazepine related adverse effects such as nausea, vomiting, and serious hematological toxicities such as aplastic anemia, agranulocytosis, eosinophilia, lymphadenopathy, and splenomegaly. Life-threatening hypersensitivity reactions such as Steven Johnson syndrome (SJS and toxic epidermal necrolysis can also occur. We hereby present a series of three cases that were prescribed carbamazepine for different indications and presented with SJS. [Int J Basic Clin Pharmacol 2015; 4(4.000: 797-801

  1. Palatal tremor after lithium and carbamazepine use: a case report

    Directory of Open Access Journals (Sweden)

    Kuruvilla Anju

    2010-06-01

    Full Text Available Abstract Introduction Palatal tremor, characterized by rhythmic contractions of the soft palate, can occur secondary to pathology in the dentato-rubro-olivary pathway, or in the absence of such structural lesions. Its pathogenesis is only partially understood. We describe a case of probable drug-induced palatal tremor. Case presentation A 27-year-old Indian man had taken carbamazepine and lithium for 7 years for the treatment of a manic episode. He presented with a one-year history of bilateral rhythmic oscillations of his soft palate and tremors of his tongue. There were no other abnormalities detected from his examination or after detailed investigation. Conclusion Palatal tremors may result from medication used in the treatment of psychiatric disorders.

  2. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    Directory of Open Access Journals (Sweden)

    Yuko Ono

    2016-01-01

    Full Text Available An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST for carbamazepine, human herpes virus-6 (HHV-6 IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times. Following treatment, liver and renal function improved and the erythema disappeared.

  3. Parkinsonisme na toevoeging van fluoxetine aan behandeling met neuroleptica of carbamazepine

    NARCIS (Netherlands)

    Touw, D J; Gernaat, H B; van der Woude, J

    1992-01-01

    This article describes three patients who developed parkinsonism when fluoxetine was added to their existing medication (neuroleptics or carbamazepine). Based on published pharmacological and neuroanatomical research we postulate a serotonin-dopamine antagonism to be operative in the development of

  4. A case of organic brain syndrome following head injury successfully treated with carbamazepine.

    Science.gov (United States)

    Bouvy, P F; van de Wetering, B J; Meerwaldt, J D; Bruijn, J B

    1988-03-01

    A case of organic brain syndrome occurring in relation to psychological stress 2 years after a severe head injury is described. Treatment with haloperidol resulted only in slight improvement. A dramatic improvement was achieved with carbamazepine.

  5. Study of efficacy of the combination of carbamazepine with nootropics on cognitive processes in epilepsy

    Directory of Open Access Journals (Sweden)

    Ivanov A.V.

    2013-03-01

    Full Text Available The authors studied the efficacy of combination of carbamazepine with nootropic drugs on cognitive processes in patients with epilepsy in experiment in order to reduce the side effects of anticonvulsant therapy. Analysis of anticonvulsant effect of the combination of drugs was carried out on 36 white nonlinear rats of both sexes weighing 160-180 g by the method of maximum electroshock, and the analysis of antiamnestic effect - using a model of retrograde amnesia on 80 white adult male rats weighing 160 - 200 g. For studying the mnemotropic activity of drug, the method of the conditioned reflex of active avoidance was used. The authors discovered that the isolated use of carbamazepine has the most negative influence on cognitive processes in animals, namely the formation of skill, memory engrams and consolidating memory trace as compared with the combined use of carbamazepine with neuroprotective drugs. It was found that the use of combinations of carbamazepine and nootropics in the experiment does not prevent the development of seizures completely, however, these combination can significantly reduce the duration of seizures (p <0.0001. Study of the effectiveness of the combined use of carbamazepine with nootropic drugs, revealed, that the tested drug combinations have a positive effect on cognitive processes and show neuroprotective effect on the brain structures of animals. The revealed effects of combined use of carbamazepine with nootropic drugs by the strength and intensity of the impact is much higher than isolated, while using carbamazepine. It was found, that the most effective combination is a combination of carbamazepine with Gliatilin.

  6. Formulation consideration and characterization of microemulsion drug delivery system for transnasal administration of carbamazepine

    OpenAIRE

    Rashmin B. Patel; Mrunali R. Patel; BHATT, Kashyap K.; Bharat G. Patel

    2013-01-01

    The purpose of the present study was to formulate and characterize carbamazepine loaded microemulsion and mucoadhesive microemulsion drug delivery system for its intranasal administration. Carbamazepine microemulsion and mucoadhesive microemulsion were prepared by titration method. The drug-loaded microemulsions were successfully prepared which contain 6% Labrafil M 1944 CS as an oily phase, 32% surfactant mixture of Cremophor RH 40: Transcutol P (4:1) and 62% (wt/wt) aqueous phase. Microemul...

  7. A comparative bioavailability of four Carbamazepine tablet formulations available in the Kenyan market.

    Science.gov (United States)

    Oluka, M O; Mitema, E S; Kibwage, I O; Kwasa, T O; Kokwaro, G O

    1996-05-01

    The relative bioavailabilities of three carbamazepine tablet formulations available in the Kenyan market (Temporal(R), Taver(R) and Carbamazepine Lincoln) compared with the innovator formulation (Tegretol(R)) were evaluated in seven healthy African volunteers (5 males, two females; aged 22-36 years), according to a randomised fourway crossover study design, following oral administration of single 200 mg doses with a three week washout period. In vitro dissolution profiles of the tablets were also evaluated. Relative bioavailabilities ((F)rel) of Temporal(R), Taver(R) and Carbamazepine Linocoln were 101.2%, 82.2% and 71.6% respectively, compared with Tegretol(R). Percent drug content dissolved in vitro after I hour were 91.3%, 75.9% and 39.3% for Temporal(R), Taver(R) and Carbamazepine Lincoln, respectively. It was concluded that Temporal(R) was bioequivalent to Tegretol(R) while Taver(R) and Carbamazepin Lincoln were bioinequivalent to Tegretol(R). Administration of Taver(R) or Carbamazepine Lincoln might lead to poor control of epileptic seizures.

  8. Definition of morphological changes of hepar, myocardium and stomach cells in rats after carbamazepin and thyotriazolin administration

    Directory of Open Access Journals (Sweden)

    Opryshko V.I.

    2012-01-01

    Full Text Available We investigated the histological changes in rats after new complex drug administration. Seventy male white rats were used for this experiment. During 90 days they received carbamazepin and thyotriazolin compound. Compound were administered orally via gavage. We observed damaging action of high dose carbamazepin on hepar, myocardium and stomach. Our data suggest that thyotriazolin reduce toxic effect of carbamazepin on hepar, myocardium and stomach.

  9. Therapeutic bioequivalency study of brand name versus generic carbamazepine.

    Science.gov (United States)

    Oles, K S; Penry, J K; Smith, L D; Anderson, R L; Dean, J C; Riela, A R

    1992-06-01

    We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency.

  10. Reductive transformation of carbamazepine by abiotic and biotic processes.

    Science.gov (United States)

    König, Anne; Weidauer, Cindy; Seiwert, Bettina; Reemtsma, Thorsten; Unger, Tina; Jekel, Martin

    2016-09-15

    The antiepileptic drug carbamazepine (CBZ) is ubiquitously present in the anthropogenic water cycle and is therefore of concern regarding the potable water supply. Despite of its persistent behavior in the aquatic environment, a redox dependent removal at bank filtration sites with anaerobic aquifer passage was reported repeatedly but not elucidated in detail yet. The reductive transformation of CBZ was studied, using abiotic systems (catalytic hydrogenation, electrochemistry) as well as biologically active systems (column systems, batch degradation tests). In catalytic hydrogenation CBZ is gradually hydrogenated and nine transformation products (TPs) were detected by liquid chromatography high-resolution mass spectrometry. 10,11-Dihydro-CBZ ((2H)-CBZ) was the major stable product in these abiotic, surface catalyzed reduction processes and turned out to be not a precursor of the more hydrogenated TPs. In the biotic reduction processes the formation of (2H)-CBZ alone could not explain the observed CBZ decline. There, also traces of (6H)-CBZ and (8H)-CBZ were formed by microbes under anaerobic conditions and four phase-II metabolites of reduced CBZ could be detected and tentatively identified. Thus, the spectrum of reduction products of CBZ is more diverse than previously thought. In environmental samples CBZ removal along an anaerobic soil passage was confirmed and (2H)-CBZ was determined at one of the sites.

  11. Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy.

    Science.gov (United States)

    Errami, Mounir; Tassa, Amina T; Galindo, Cristi L; Skinner, Michael A; Hill, Joseph A; Garner, Harold R

    2010-06-23

    β-adrenergic signaling is involved in the development of cardiac hypertrophy (CH), justifying the use of β-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the β-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ), an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO)-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB) (P=0.07). When carbamazepine was given in combination with the antibiotic doxycycline (DOX), which inhibits matrix metalloproteinases (MMPs), therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze -pine as a β-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB) were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a β-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA) as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional β-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as additional

  12. Uptake of carbamazepine by rhizomes and endophytic bacteria of Phragmites australis.

    Science.gov (United States)

    Sauvêtre, Andrés; Schröder, Peter

    2015-01-01

    Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely in Europe and North America. In the environment, it is found as a persistent and recalcitrant contaminant, being one of the most prominent hazardous pharmaceuticals and personal care products in effluents of wastewater treatment plants. Phragmites australis is one of the species with both, the highest potential of detoxification and phytoremediation. It has been used successfully in the treatment of industrial and municipal wastewater. Recently, the identification of endophytic microorganisms from different plant species growing in contaminated sites has provided a list of candidates which could be used as bio-inoculants for bioremediation of difficult compounds. In this study, Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days the plants had removed 90% of the initial concentration. Endophytic bacteria were isolated from these plants and further characterized. Phylogenetic analysis based on 16S rDNA sequencing revealed that the majority of these isolates belong to three groups: Proteobacteria, Actinobacteria, and Bacteroidetes. Carbamazepine uptake and plant growth promoting (PGP) traits were analyzed among the isolates. Ninety percent of the isolates produce indole acetic acid (IAA) and all of them possess at least one of the PGP traits tested. One isolate identified as Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP traits. Rhizobium daejeonense can remove carbamazepine and produces 23 μg/mL of IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show high siderophore production and phosphate solubilization. Alone or in combination, these isolates might be applied as inoculates in constructed wetlands in order to enhance the phytoremediation of carbamazepine during wastewater treatment.

  13. Uptake of Carbamazepine by rhizomes and endophytic bacteria of Phragmites australis

    Directory of Open Access Journals (Sweden)

    Andres eSauvetre

    2015-02-01

    Full Text Available Carbamazepine is an antiepileptic and mood-stabilizing drug which is used widely in Europe and North America. In the environment, it is found as a persistent and recalcitrant conta¬mi-nant, being one of the most prominent hazardous pharmaceuticals and personal care products (PPCPs in effluents of wastewater treatment plants (WWTPs. Phragmites australis is one of the species with both, the highest potential of detoxification and phytoremediation. It has been used successfully in the treatment of industrial and municipal wastewater. Recently, the identification of endophytic micro¬organisms from different plant species growing in contaminated sites has provided a list of candidates which could be used as bio-inoculants for bioremediation of difficult compounds. In this study, Phragmites australis plants were exposed to 5 mg/L of carbamazepine. After 9 days the plants had removed 90% of the initial concentration. Endophytic bacteria were isolated from these plants and further characterized. Phylogenetic analysis based on 16S rDNA sequencing revealed that the majority of these isolates belong to three groups: Proteobacteria, Actinobacteria and Bacteroidetes. Carbamazepine uptake and plant growth promoting (PGP traits were analyzed among the isolates. Ninety percent of the isolates produce indole acetic acid (IAA and all of them possess at least one of the PGP traits tested. One isolate identified as Chryseobacterium taeanense combines good carbamazepine uptake and all of the PGP traits. Rhizobium daejeonense can remove carbamazepine and produces 23 µg/mL of IAA. Diaphorobacter nitroreducens and Achromobacter mucicolens are suitable for carbamazepine removal while both, Pseudomonas veronii and Pseudomonas lini show high siderophore production and phosphate solubilization. Alone or in combination, these isolates might be applied as inoculates in constructed wetlands in order to enhance the phyto-remediation of carbamazepine during wastewater

  14. Pharmacokinetic and pharmacodynamic drug interactions of carbamazepine and glibenclamide in healthy albino Wistar rats

    Directory of Open Access Journals (Sweden)

    S Prashanth

    2011-01-01

    Full Text Available Aims: To find out the pharmacokinetic and pharmacodynamic drug interaction of carbamazepine, a protype drug used to treat painful diabetic neuropathy with glibenclamide in healthy albino Wistar rats following single and multiple dosage treatment. Materials and Methods: Therapeutic doses (TD of glibenclamide and TD of carbamazepine were administered to the animals. The blood glucose levels were estimated by GOD/POD method and the plasma glibenclamide concentrations were estimated by a sensitive RP HPLC method to calculate pharmacokinetic parameters. Results: In single dose study the percentage reduction of blood glucose levels and glibenclamide concentrations of rats treated with both carbamazepine and glibenclamide were significantly increased when compared with glibenclamide alone treated rats and the mechanism behind this interaction may be due to inhibition of P-glycoprotein mediated transport of glibenclamide by carbamazepine, but in multiple dose study the percentage reduction of blood glucose levels and glibenclamide concentrations were reduced and it may be due to inhibition of P-glycoprotein mediated transport and induction of CYP2C9, the enzyme through which glibenclamide is metabolised. Conclusions: In the present study there is a pharmacokinetic and pharmacodynamic interaction between carbamazepine and glibenclamide was observed. The possible interaction involves both P-gp and CYP enzymes. To investigate this type of interactions pre-clinically are helpful to avoid drug-drug interactions in clinical situation.

  15. Nonconvulsive status epilepticus precipitated by carbamazepine presenting as dissociative and affective disorders in adolescents.

    Science.gov (United States)

    Marini, Carla; Parmeggiani, Lucio; Masi, Gabriele; D'Arcangelo, Gianluca; Guerrini, Renzo

    2005-08-01

    Nonconvulsive status epilepticus can be confused with psychiatric disorders. Inappropriate drug treatment can represent a precipitating factor. We describe two patients with idiopathic generalized epilepsy in whom nonconvulsive status epilepticus, aggravated by carbamazepine, was misdiagnosed as psychiatric disorder. A 14-year-old girl experienced a tonic-clonic seizure at age 12 years preceded by monthly episodes of confusion with awkward behavior since age 9 years. She was treated with carbamazepine, and the episodes of confusion became more frequent, leading to a diagnosis of dissociative disorder. An electroencephalogram during one of these episodes revealed nonconvulsive status epilepticus. Substitution of carbamazepine with valproic acid controlled the episodes of status epilepticus. A 23-year-old woman presented at age 16 years with a tonic-clonic seizure. Since early adolescence, she had had episodes of depressive mood, worsening of school performances, and facial tics. Carbamazepine treatment caused worsening of the depressive episodes and facial tics. An electroencephalogram during a typical episode revealed nonconvulsive status epilepticus. Carbamazepine substitution with valproate led to seizure freedom and behavioral improvement. Nonconvulsive status epilepticus should be suspected and searched for in patients with epileptic seizures and ictal or fluctuating behavioral disorders.

  16. Enhanced biodegradation of carbamazepine after UV/H2O2 advanced oxidation.

    Science.gov (United States)

    Keen, Olya S; Baik, Seungyun; Linden, Karl G; Aga, Diana S; Love, Nancy G

    2012-06-05

    Carbamazepine is one of the most persistent pharmaceutical compounds in wastewater effluents due to its resistance to biodegradation-based conventional treatment. Advanced oxidation can efficiently degrade carbamazepine, but the toxicity and persistence of the oxidation products may be more relevant than the parent. This study sets out to determine whether the products of advanced oxidation of carbamazepine can be biotransformed and ultimately mineralized by developing a novel methodology to assess these sequential treatment processes. The methodology traces the transformation products of the (14)C-labeled carbamazepine during UV/hydrogen peroxide advanced oxidation and subsequent biotransformation by mixed, undefined cultures using liquid scintillation counting and liquid chromatography with radioactivity, mass spectrometry, and UV detectors. The results show that the oxidation byproducts of carbamazepine containing a hydroxyl or carbonyl group can be fully mineralized by a mixed bacterial inoculum. A tertiary treatment approach that includes oxidation and biotransformation has the potential to synergistically mineralize persistent pharmaceutical compounds in wastewater treatment plant effluents. The methodology developed for this study can be applied to assess the mineralization potential of other persistent organic contaminants.

  17. Comparative efficacy of phenytoin, steroid and carbamazepine in herpes zoster and post herpetic neuralgia

    Directory of Open Access Journals (Sweden)

    Agarwal S

    1991-01-01

    Full Text Available Three hundred patients of different ages were sequentially assigned three therapy groups (100 in each group viz. phenytoin, steroid (prednisolone and carbamazepine. Effect of these drugs on herpes zoster neuralgia and in prevention of post herpetic neuralgia was studied. Phenytoin was found to be superior to both steroid and carbamazepine in relieving the pain of herpes zoster and in reducing the incidence of post herpetic neuralgia. Only 16.1% of the patients in phenytoin treated group developed post herpetic neuralgia lasting for 2-4 weeks while 22.7% and 29.6% of the steroid and carbamazepine treated patients respectively developed post herpetic neuralgia and that too lasting for longer duration. No patient under 40 years developed post herpetic neuralgia.

  18. Degradation of orange dyes and carbamazepine by soybean peroxidase immobilized on silica monoliths and titanium dioxide.

    Science.gov (United States)

    Calza, Paola; Zacchigna, Dario; Laurenti, Enzo

    2016-12-01

    In this paper, the removal of three common dyes (orange I, orange II, and methylorange) and of the anticonvulsant drug carbamazepine from aqueous solutions by means of enzymatic and photocatalytic treatment was studied. Soybean peroxidase (SBP) was used as biocatalyst, both free in solution and immobilized on silica monoliths, and titanium dioxide as photocatalyst. The combination of the two catalysts led to a faster (about two to four times) removal of all the orange dyes compared to the single systems. All the dyes were completely removed within 2 h, also in the presence of immobilized SBP. As for carbamazepine, photocatalytic treatment prevails on the enzymatic degradation, but the synergistic effect of two catalysts led to a more efficient degradation; carbamazepine's complete disappearance was achieved within 60 min with combined system, while up to 2 h is required with TiO2 only.

  19. Lamotrigine versus carbamazepine in treating newly diagnosed epilepsy:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    LIU Ya; PENG Ya-Wen; ZHOU Ke-Cheng; QU Cheng-Hao; HU Wei

    2014-01-01

    First-line therapy for newly diagnosed epilepsy (e.g. carbamazepine)is generally considered effective.However,in a significant proportion of patients (especially in the elderly),us-age may be limited by unwanted adverse events.To synthesize ev-idence regarding efficacy and tolerability of lamotrigine as first line, monotherapy or prophylactic antiepileptic. MEDLINE, PsycINFO,Scopus,EMBASE,and the Cochrane Central Register of Controlled Trials (CENTRAL)were searched from inception to June 2014.Randomised controlled trials (RCTs)comparing lam-otrigine with carbamazepine monotherapy for newly diagnosed epi-lepsy.Eligible studies were independently selected and methodo-logical quality was independently evaluated by two reviewers. Effects were summarized using standardized hazard ratio (HR)or odds ratio (OR)with suitable effect models.Pre-specified sensi-tivity analyses were performed to explain heterogeneity.Nine stud-ies involving 2793 participants met the inclusion criteria.The effects of lamotrigine compared with carbamazepine in patients with newly diagnosed seizures were investigated in all studies.We found that carbamazepine was inferior in comparison to lamotrigine when measuring the proportion of remaining seizure free in the elderly (hazard ratio (HR)1.71;95%confidence interval (CI) 1.27 to 2.29)but notthe children and the adult.There was strong evidence for the tolerability profile of lamotrigine compared with carbamazepine in the Retention rates (HR 1 .67;95%CI 1 . 43 to 1.94).Moreover,lamotrigine lead to less adverse events. Lamotrigine and carbamazepine showed similar efficacy on newly diagnosed epilepsy but better efficacy in the elderly than carbam-azepine.Furthermore,lamotrigine was better tolerated.

  20. Association of HLA-BFNx011502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians

    Directory of Open Access Journals (Sweden)

    Mehta Timir

    2009-01-01

    Full Text Available Background: Stevens-Johnson Syndrome (SJS and toxic epidermal necrolysis are severe cutaneous reactions caused by certain drugs, including antiepileptic carbamazepine. A strong association has been reported between human leucocyte antigen (HLA-BFNx011502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-BFNx011502 is not a universal marker but is ethnicity-specific for Asians. Aim: To study the association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients. Methods: Eight individuals who fulfilled the diagnostic criteria of SJS induced by carbamazepine were identified and HLA-B molecular typing was performed. HLA-B genotyping was carried out by polymerase chain reaction using sequence-specific primers. Results: Out of eight patients studied for genotype, six patients were found to have the HLA-BFNx011502 allele. Conclusion: This study suggests an association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients.

  1. Biomimetic oxidation of carbamazepine with hydrogen peroxide catalyzed by a manganese porphyrin

    Energy Technology Data Exchange (ETDEWEB)

    Neves, Claudia M.B.; Simoes, Mario M.Q.; Domingues, Fernando M.J.; Neves, M. Graca P.M.S.; Cavaleiro, Jose A.S., E-mail: msimoes@ua.pt [Dept. de Quimica, QOPNA, Universidade de Aveiro (Portugal)

    2012-07-01

    This laboratory project is planned for an undergraduate chemistry laboratory in which students prepare a manganese porphyrin able to mimic the oxidative metabolism of carbamazepine, one of the most frequently prescribed drugs in the treatment of epilepsy. The in vitro oxidation of carbamazepine results in the formation of the corresponding 10,11-epoxide, the main in vivo metabolite. The reaction is catalyzed by manganese porphyrin in the presence of H{sub 2}O{sub 2}, an environmentally-friendly oxidant. Through this project students will develop their skills in organic synthesis, coordination chemistry, chromatographic techniques such as TLC and HPLC, UV-visible spectrophotometry, and NMR spectroscopy. (author)

  2. Biomimetic oxidation of carbamazepine with hydrogen peroxide catalyzed by a manganese porphyrin

    Directory of Open Access Journals (Sweden)

    Cláudia M. B. Neves

    2012-01-01

    Full Text Available This laboratory project is planned for an undergraduate chemistry laboratory in which students prepare a manganese porphyrin able to mimic the oxidative metabolism of carbamazepine, one of the most frequently prescribed drugs in the treatment of epilepsy. The in vitro oxidation of carbamazepine results in the formation of the corresponding 10,11-epoxide, the main in vivo metabolite. The reaction is catalyzed by manganese porphyrin in the presence of H2O2, an environmentally-friendly oxidant. Through this project students will develop their skills in organic synthesis, coordination chemistry, chromatographic techniques such as TLC and HPLC, UV-visible spectrophotometry, and NMR spectroscopy.

  3. A retrospective study of carbamazepine therapy in the treatment of idiopathic generalised epilepsy

    LENUS (Irish Health Repository)

    O'Connor, G

    2011-05-01

    Objective: The exacerbation of idiopathic generalised epilepsy (IGE) by some anti-epileptic drugs (AEDs) such as carbamazepine (CBZ) has been well documented. However, it is unclear whether IGE is always worsened by the use of CBZ, or whether some patients with IGE benefit from its use. \\r\

  4. Intrauterine exposure to carbamazepine and specific congenital malformations : systematic review and case-control study

    NARCIS (Netherlands)

    Jentink, Janneke; Dolk, Helen; Loane, Maria A.; Morris, Joan K.; Wellesley, Diana; Garne, Ester; de Jong-van den Berg, Lolkje

    2010-01-01

    Objective To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. Design A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. Setting Review of P

  5. Epidemiology, pathophysiology and putative genetic basis of carbamazepine- and oxcarbazepine-induced hyponatremia

    NARCIS (Netherlands)

    Berghuis, B; de Haan, G-J; van den Broek, M P H; Sander, J W; Lindhout, D; Koeleman, B P C

    2016-01-01

    The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to

  6. A comparative study of thyroid status of patients on phenytoin, carbamazepine and valproate monotherapy

    Directory of Open Access Journals (Sweden)

    Dinesh K. Dhodi

    2016-04-01

    Conclusions: Valproate monotherapy does not alter serum levels of thyroid hormones. On the contrary, alterations of thyroid hormone function were seen in patients treated with carbamazepine and phenytoin. However, all the patients were euthyroid and were not associated with clinical or even subclinical hypothyroidism. [Int J Basic Clin Pharmacol 2016; 5(2.000: 362-365

  7. Visualizing solvent mediated phase transformation behavior of carbamazepine polymorphs by principal component analysis

    DEFF Research Database (Denmark)

    Tian, Fang; Rades, Thomas; Sandler, Niklas

    2008-01-01

    The purpose of this research is to gain a greater insight into the hydrate formation processes of different carbamazepine (CBZ) anhydrate forms in aqueous suspension, where principal component analysis (PCA) was applied for data analysis. The capability of PCA to visualize and to reveal simplifie...

  8. Relaxation and crystallization of amorphous carbamazepine studied by terahertz pulsed spectroscopy

    DEFF Research Database (Denmark)

    Zeitler, J Axel; Taday, Philip F; Pepper, Michael;

    2007-01-01

    At the example of carbamazepine the crystallization of a small organic molecule from its amorphous phase was studied using in situ variable temperature terahertz pulsed spectroscopy (TPS). Even though terahertz spectra of disordered materials in the glassy state exhibit no distinct spectral featu...

  9. Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study

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    Thaiana Aragão Santana

    Full Text Available CONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV.DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life.RESULTS:None of the ten patients (0% presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life.CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population.

  10. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

    Institute of Scientific and Technical Information of China (English)

    Parthasarathy Govindasamy; Bhaskar Reddy Kesavan; Jayaveera Korlakunta Narasimha

    2013-01-01

    Objective:To achieve transbuccal release of carbamazepine by loading in unidirectional release mucoadhesive buccal patches. Methods:Buccal patches of carbamazepine with unidirectional drug release were prepared using hydroxypropyl methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by solvent casting method. Water impermeable backing layer (Pidilite® Biaxially-oriented polypropylene film) of patches provided unidirectional drug release. They were evaluated for thickness, mass uniformity, surface pH and folding endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance above 250) were evaluated further for swelling studies, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, ex vivo permeation, accelerated stability studies and FTIR and XRD spectral studies. Results: The ex vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s. The in vitro drug release studies revealed that formulation FA8 released 84%and FB16 released 99.01%of drug in 140 min. Conclusions: The prepared unidirectional buccal patches of carbamazepine provided a maximum drug release within specified mucoadhesion period and it indicates a potential alternative drug delivery system for systemic delivery of carbamazepine.

  11. Effect of pomegranate juice pre-treatment on the transport of carbamazepine across rat intestine

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    D Adukondalu

    2010-12-01

    Full Text Available "n  "nBackground and the purpose of the study: Many drug substances along with a variety of naturally occurring dietary or herbal components interact with the CYP enzyme system.The present study was aimed to investigate the effect of pomegranate juice pre-treatment on the transport of carbamazepine across the rat intestine "nMethods: The transport of carbamazepine across different parts of rat intestine was studied by everted and non-everted sac methods. The control and pomegranate juice (10 ml Kg-1 for 7 days pre-treated rats were sacrificed and isolated the intestine. The sacs of intestine were prepared, treated with carbamazepine solution and then placed in dulbeccos buffer. Samples were collected periodically and the drug content was estimated using HPLC. Results and conclusion: The results show that there was a significant (p<0.05 difference in the transport of carbamazepine from the intestinal sacs of pretreated with pomegranate juice and control. It seems that pomegranatejuice might have induced CYP3A4enzymes and hence drug is extensively metabolized.

  12. Carbamazepine- or Oxcarbazepine-Induced Hyponatraemia or Leucopenia, or Both, in Residents with a Developmental Disability.

    Science.gov (United States)

    Heiskala, Hannu; Tokola, Ritta; Tammisto, Paavo; Kaski, Markus

    1997-01-01

    A study investigated the prevalence of carbamazepine- or oxcarbazepine-induced hyponatraemia and leucopenia in 334 Finnish individuals with developmental disabilities. Medication with these drugs resulted in significantly lower levels of serum sodium and counts of blood leucocytes. Because of difficulties in expressing their symptoms, this…

  13. Multivariate control charts based on net analyte signal (NAS) and Raman spectroscopy for quality control of carbamazepine.

    Science.gov (United States)

    Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

    2011-10-31

    Raman spectroscopy and control charts based on the net analyte signal (NAS) were applied to polymorphic characterization of carbamazepine. Carbamazepine presents four polymorphic forms: I-IV (dihydrate). X-ray powder diffraction was used as a reference technique. The control charts were built generating three charts: the NAS chart that corresponds to the analyte of interest (form III in this case), the interference chart that corresponds to the contribution of other compounds in the sample and the residual chart that corresponds to nonsystematic variations. For each chart, statistical limits were developed using samples within the quality specifications. It was possible to identify the different polymorphic forms of carbamazepine present in pharmaceutical formulations. Thus, an alternative method for the quality monitoring of the carbamazepine polymorphic forms after the crystallization process is presented.

  14. Withdrawal syndrome and hypomagnesaemia and in a newborn exposed to valproic acid and carbamazepine during pregnancy.

    Science.gov (United States)

    Satar, Mehmet; Ortaköylü, Kadir; Batun, İnci; Yıldızdaş, Hacer Y; Özlü, Ferda; Demir, Hüsnü; Topaloğlu, Ali Kemal

    2016-06-01

    The usage of drugs during pregnancy affect the fetus and the newborn. In this report, we present findings from a newborn baby, whose mother was epileptic, and was under the treatment of valproic acid and carbamazepine during pregnancy. We have found symptoms of withdrawal syndrome, hyponatremia and feeding problem, which was most probably related to exposure to the mentioned drugs. We have also diagnosed hypomagnesaemia and atrial septal defect 4 milimeters in diameter. There are already many reports about the side effects of valproic acid and carbamazepine usage during pregnancy. To the best of our knowledge, hypomagnesaemia has not yet been reported as a side effect. We think that hypomagnesaemia is also related to the usage of antiepileptics.

  15. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review☆

    Institute of Scientific and Technical Information of China (English)

    Prasanna A. Datar

    2015-01-01

    Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharma-cology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application). Various methods such as GC, LC-MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quan-titative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enu-merates metabolites, and impurities reported so far.

  16. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

    Directory of Open Access Journals (Sweden)

    Prasanna A. Datar

    2015-08-01

    Full Text Available Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application. Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and quantitative analysis of carbamazepine in biological samples throughout all phases of clinical research and quality control. The article incorporates various reported methods developed to help analysts in choosing crucial parameters for new method development of carbamazepine and its derivatives and also enumerates metabolites, and impurities reported so far.

  17. Carbamazepine suppresses synchronized afterdischarging in disinhibited immature rat hippocampus in vitro.

    Science.gov (United States)

    Smith, K L; Swann, J W

    1987-01-06

    Bath application of therapeutic concentrations of the anticonvulsant carbamazepine suppressed penicillin-induced synchronized afterdischarging in immature rat CA3 hippocampal pyramidal cells. Afterdischarging was completely abolished in all preparations at a concentration of 30 microM (IC50 = 8.5 +/- 1.4 microM; mean +/- S.E.M.). The duration of the preceding epileptiform burst was not altered at this concentration and was diminished by only 24.4 +/- 1.2% at a supratherapeutic concentration of 100 microM. These results suggest that a carbamazepine-sensitive neurophysiological mechanism distinct from those responsible for epileptiform burst generation plays a key role in the generation of afterdischarges in developing hippocampus.

  18. Lupus and pulmonary nodules consistent with bronchiolitis obliterans organizing pneumonia induced by carbamazepine in a man

    OpenAIRE

    Awatef Kelati; Salim Gallouj; Mariame Meziane; Fatima Zahra Mernissi

    2016-01-01

    Several drugs have been implicated in the induction of systemic lupus erythematosus (SLE), but there are only some observations of carbamazepine induced SLE since the first case described in 1966, this drug has also been implicated in the induction of other disorders and rarely pulmonary toxicity; but the occurrence of two rare side effects of this drug: the induced SLE and pulmonary nodules consistent with the bronchiolitis obliterans organizing pneumonia in same patient is really unusual an...

  19. Carbamazepine inhibits angiotensin I-converting enzyme, linking it to the pathogenesis of temporal lobe epilepsy

    Science.gov (United States)

    Almeida, S S; Naffah-Mazzacoratti, M G; Guimarães, P B; Wasinski, F; Pereira, F E G; Canzian, M; Centeno, R S; Carrete, H; Yacubian, E M; Carmona, A K; Vieira, R F F; Nakaie, C R; Sabatini, R A; Perosa, S R; Bacurau, R F P; Gouveia, T L F; Gallo, G; Würtele, M; Cavalheiro, E A; Silva, J A; Pesquero, J B; Araujo, R C

    2012-01-01

    We find that a common mutation that increases angiotensin I-converting enzyme activity occurs with higher frequency in male patients suffering from refractory temporal lobe epilepsy. However, in their brains, the activity of the enzyme is downregulated. As an explanation, we surprisingly find that carbamazepine, commonly used to treat epilepsy, is an inhibitor of the enzyme, thus providing a direct link between epilepsy and the renin–angiotensin and kallikrein–kinin systems. PMID:22832858

  20. Recrystallization of Commercial Carbamazepine Samples—A Strategy to Control Dissolution Variability

    OpenAIRE

    Felicia Flicker; Eberle, Veronika A.; Gabriele Betz

    2012-01-01

    Physical properties of commercial carbamazepine (CBZ) samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were recrystallized in ethanol solution containing 1% polyvinylpyrrolidone (PVP). CBZ samples were analyzed by disk intrinsic dissolution rate (DIDR), X-ray powder diffraction (XRPD), differenti...

  1. Simultaneous Quantification of Three Polymorphic Forms of Carbamazepine in the Presence of Excipients Using Raman Spectroscopy

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    Marco Farias

    2014-09-01

    Full Text Available The occurrence of polymorphic transitions is a serious problem for pharmaceutical companies, because it can affect the bioavailability of the final product. With several known polymorphic forms carbamazepine is one of the most problematic drugs in this respect. Raman spectroscopy is a vibrational technique that is becoming very important in the pharmaceutical field, mainly due to its highly specific molecular fingerprint capabilities and easy use as a process analytical tool. However, multivariate methods are necessary both for identification and quantification. In this work an analytical methodology using Raman spectroscopy and interval Partial Least Squares Regression (iPLS, was developed in order to quantify mixtures of carbamazepine polymorphs in the presence of the most common excipients. The three polymorphs CBZ I, CBZ III and CBZ DH (which is a dihydrate were synthesized and characterized by PXRD and DSC. Subsequently, tablets were manufactured using excipients and 15 different mixtures of carbamazepine polymorphs. The iPLS model presented average prediction validation errors of 1.58%, 1.04% and 0.22% wt/wt, for CBZ I, CBZ III and CBZ DH, respectively, considering the whole mass of the tablet. The model presents a good prediction capacity and the proposed methodology could be used to perform quality control in final products.

  2. GC-MS analysis and ecotoxicological risk assessment of triclosan, carbamazepine and parabens in Indian rivers.

    Science.gov (United States)

    Ramaswamy, Babu Rajendran; Shanmugam, Govindaraj; Velu, Geetha; Rengarajan, Bhuvaneshwari; Larsson, D G Joakim

    2011-02-28

    Pharmaceutical and personal care products are used extensively worldwide and their residues are frequently reported in aquatic environments. In this study, antiepileptic, antimicrobial and preservative compounds were analyzed in surface water and sediment from the Kaveri, Vellar and Tamiraparani rivers, and in the Pichavaram mangrove in India by gas chromatography-mass spectrometry (GC-MS). The mean concentration of carbamazepine recorded in the Kaveri River water (28.3 ng/L) was higher than in the other rivers and the mangrove. Because carbamazepine is used only in human drugs, this may reflect the relative contributions of human excretions/sewage in these rivers. The mean triclosan level in the Tamiraparani River (944 ng/L) was an order of magnitude greater than in the other water systems, and the concentrations at two of the sites reported here (3800-5160 ng/L) are, to our best knowledge, among the highest detected in surface waters. Sediment levels were, however, comparable with other sites. We conclude that industrial releases are likely major contributors of triclosan into this river system. Among parabens, ethyl paraben was predominantly observed. Hazard Quotients suggest greater environmental risks for triclosan than for carbamazepine and parabens. This is the first study on antiepileptic, antimicrobial and preservatives in rivers and mangroves from India.

  3. Seromucosal transport of intravenously administered carbamazepine is not enhanced by oral doses of activated charcoal in rats.

    Science.gov (United States)

    Eyer, Florian; Jung, Nicole; Neuberger, Heidi; Witte, Andreas; Poethko, Thorsten; Henke, Julia; Zilker, Thomas

    2008-03-01

    The fate of carbamazepine after intravenous injection in rats (n = 24) and the influence of activated charcoal on the kinetics was investigated. After randomization to four groups (n = 6, each), plasma concentration and the quantities of carbamazepine and metabolites excreted into bile, urine and intestine were determined using an in situ perfusion model of the small intestine (Ringer's solution) with or without orally administered activated charcoal (AC+; AC-) and with or without bile duct cannulation (BD+; BD-). The cumulative amount of carbamazepine and metabolites exsorbed into the small intestine within 3.5 hr after intravenous injection was about 15% in BD- animals and about 3% in BD+ animals. About 20% of the dose was detected in the externalized bile. Activated charcoal did not influence the amount exsorbed into the small intestine. Terminal half-life in plasma ranged from 159 min. to 194 min. within the four treatment groups without statistical significant difference (P = 0.751). Correspondingly, the area under the curve did not vary significantly and ranged between 1.13 and 1.41 g/min./l (P = 0.378). Excretion of carbamazepine and metabolites into urine varied between 3% and 6% of dose within all groups and showed close correlation with diuresis. In an identical experimental approach using a 2-fold intestinal perfusion rate (50 ml/hr; n = 8), no fundamental changes compared to the main experiment regarding pharmacokinetics of carbamazepine were observed. The lack of effect of activated charcoal on the elimination of carbamazepine and metabolites must be contributed to the small amount of the drug being exsorbed into the intestine and may be further influenced by reduced intestinal permeability of carbamazepine and metabolites or inadequate luminal stirring.

  4. Development and Validation of HPTLC Method for Estimation of Carbamazepine in Formulations and Its In Vitro Release Study

    Directory of Open Access Journals (Sweden)

    Rashmin B. Patel

    2011-01-01

    Full Text Available A new, simple, and rapid high-performance thin-layer chromatographic method was developed and validated for quantitative determination of Carbamazepine. Carbamazepine was chromatographed on silica gel 60 F254 TLC plate using ethyl acetate-toluene-methanol (5.0 + 4.0 + 1.0 v/v/v as mobile phase. Carbamazepine was quantified by densitometric analysis at 285 nm. The method was found to give compact spots for the drug (Rf=0.47 ± 0.01. The linear regression analysis data for the calibration plots showed good linear relationship with r2=.9995 in the concentration range 100–600 ng/spot. The method was validated for precision, recovery, repeatability, and robustness as per the International Conference on Harmonization guidelines. The minimum detectable amount was found to be 16.7 ng/spot, whereas the limit of quantitation was found to be 50.44 ng/spot. Statistical analysis of the data showed that the method is precise, accurate, reproducible, and selective for the analysis of Carbamazepine. The method was successfully employed for the estimation of equilibrium solubility, quantification of Carbamazepine as a bulk drug, in commercially available preparation, and in-house developed mucoadhesive microemulsion formulations and solution.

  5. Effects of Oxcarbazepine Versus Carbamazepine on Tinnitus: A Randomized Double-Blind Placebo-Controlled Clinical Trial

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    Ehsan Kazemnejad

    2012-07-01

    Full Text Available Background: It is still a challenge to find an effective treatment for tinnitus. The aim of this study was the evaluation of carbamazepine and oxcarbazepine effects on tinnitus.Methods: In a randomized double–blind clinical trial, 57 patients who were visited in a university hospital due to chronic non-pulsatile tinnitus, were randomized in three groups and treated with carbamazepine (300-600 mg/day, oxcarbazepine (450-900 mg/day and placebo for 12 weeks. Visual analogue scale (VAS and tinnitus severity index (TSI were measured in all subjects in the beginning and at the end of the 8th and 12th weeks of the trial. Data was analyzed by repeated measure analysis, paired and independent t-test.Results: Among 51 participants who completed the trial course (28 men, 23 women, carbamazepine, oxcarbazepine and placebo decreased tinnitus severity in 56.6%, 46.2% and 38.5% of patients according to VAS, and in 61.1%, 58.8% and 50% of patients according to TSI, respectively. The effects of carbamazepine and oxcarbazepine were better in the first 8 weeks of treatment. However, their effect on tinnitus did not show any statistical difference in comparison with placebo (P = 0.34, P = 0.28.Conclusion: Carbamazepine and oxcarbazepine are not more effective than placebo in decreasing tinnitus severity.

  6. Influence of environmental conditions on the kinetics and mechanism of dehydration of carbamazepine dihydrate.

    Science.gov (United States)

    Han, J; Suryanarayanan, R

    1998-11-01

    The object of this project was to study the influence of temperature and water vapor pressure on the kinetics and mechanism of dehydration of carbamazepine dihydrate and to establish the relationship between the dehydration mechanism and the solid-state of the anhydrous phase formed. Three experimental techniques were utilized to study the kinetics of dehydration of carbamazepine dihydrate (C15H12N2O.2H2O)-thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and variable temperature powder X-ray diffractometry (VTXRD). These techniques respectively provide information about the changes in weight, heat flow and solid-state (phase) during the dehydration process. The instrumental setup was modified so that simultaneous control of both the temperature and the water vapor pressure was possible. The experiments were carried out at different temperatures, ranging from 26 to 64 degrees C. In the absence of water vapor, the dehydration followed the 2-dimensional phase boundary controlled model at all the temperatures studied. In the next stage, the water vapor pressure was altered while the studies were carried out at a single temperature of 44 degrees C. The dehydration was 2-dimensional phase boundary controlled at water vapor pressures or = 12.0 torr. In the former case, the anhydrous phase formed was X-ray amorphous while it was the crystalline anhydrous gamma-carbamazepine in the latter. Thus a relationship between the mechanism of dehydration and the solid-state of the product phase was evident. The dehydration conditions influence not only the mechanism but also the solid-state of the anhydrous phase formed. While the techniques of TGA and DSC have found extensive use in studying dehydration reactions, VTXRD proved to be an excellent complement in characterizing the solid-states of the reactant and product phases.

  7. Carbamazepine in treatment of visual hallucinations: A case of chronic hallucinatory psychosis

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    Sayantanava Mitra

    2015-01-01

    Full Text Available Visual hallucinations are commonly present in various neurological and psychiatric conditions such as schizophrenia and other hallucinatory psychosis. Current conceptualization of hallucinations assume pattern completion model of thalamus to be responsible for the origin of this type of the perceptual abnormality and proposes that central inhibition of such circuits may treat hallucinations. We present a case of chronic hallucinatory psychosis with significantly distressing visual hallucinations, resistant to antipsychotics, which successfully responded to carbamazepine. This case illustrates the novel use of an antiepileptic in the treatment of resistant visual hallucinations. Targeted therapy of this kind can be considered in the future, although more evidence is required in this field.

  8. Lupus and pulmonary nodules consistent with bronchiolitis obliterans organizing pneumonia induced by carbamazepine in a man

    Directory of Open Access Journals (Sweden)

    Awatef Kelati

    2016-10-01

    Full Text Available Several drugs have been implicated in the induction of systemic lupus erythematosus (SLE, but there are only some observations of carbamazepine induced SLE since the first case described in 1966, this drug has also been implicated in the induction of other disorders and rarely pulmonary toxicity; but the occurrence of two rare side effects of this drug: the induced SLE and pulmonary nodules consistent with the bronchiolitis obliterans organizing pneumonia in same patient is really unusual and -to our knowledge- the second observation reported in the literature.

  9. [Gabapentin treatment in a female patient with panic disorder and adverse effects under carbamazepine during benzodiazepine withdrawal].

    Science.gov (United States)

    Himmerich, Hubertus; Nickel, Thomas; Dalal, Mira A; Müller, Marianne B

    2007-03-01

    Despite their addictive potential, benzodiazepines belong to the most often prescribed drugs. We report on a patient with alprazolam dependence, who initially was treated with carbamazepine because of severe withdrawal symptoms. Due to liver enzyme elevation related to carbamazepine, we had to stop this treatment and instead of that started gabapentin treatment. Under this new therapy, the patient showed a dramatic relief of withdrawal symptoms and of the panic attacks recurring during withdrawal. Hence, due to their effectiveness and tolerability, newer anticonvulsants could be considered as medication for benzodiazepine withdrawal and as an alternative for benzodiazepine treatment in panic disorders.

  10. Fate of carbamazepine and anthracene in soils watered with UV-LED treated wastewaters.

    Science.gov (United States)

    Chevremont, A-C; Boudenne, J-L; Coulomb, B; Farnet, A-M

    2013-11-01

    Water disinfection technologies based on ultraviolet (UV) radiations emitted by Light-Emitting Diodes (LED), as a wastewater tertiary treatment, have been shown to be promising for water reuse. Here, we assessed the fate of two ubiquitous pollutants, carbamazepine and anthracene, in soil watered with either UV-LED treated wastewaters or irrigation water. After 3 months, anthracene and carbamazepine were transformed two and three times faster respectively, in soils watered with UV-LED wastewater than in soils watered with tap water (probably because of the addition of organic matter by the effluent). Laccase activity was induced in the presence of the pollutants and anthraquinone was found as anthracene product of oxidation by laccases. Moreover, the addition of these pollutants into soil did not affect the functional diversity of autochthonous microbial communities assessed by Ecolog plates. Cellulase, protease and urease activities increased in soils watered with UV-LED treated wastewaters (UV-LED WW), showing transformation of organic matter from the effluent and lipase activity increased by anthracene addition, confirming the potential role of these enzymes as indicators of hydrocarbon contamination.

  11. Generation of 1:1 Carbamazepine:Nicotinamide cocrystals by spray drying.

    Science.gov (United States)

    Patil, Shashank P; Modi, Sameer R; Bansal, Arvind K

    2014-10-01

    The present study investigates the potential of spray drying as a technique for generation of pharmaceutical cocrystals. Carbamazepine-Nicotinamide cocrystal (CNC) was chosen as model cocrystal system for this study. Firstly, CNC was generated using liquid assisted grinding and used for generation of phase solubility diagram (PSD) and ternary phase diagram (TPD). Both PSD and TPD were carefully evaluated for phase behavior of CNC when equilibrated with solvent. The undersaturated region with respect to CNC, as depicted by TPD, was selected as target region to initiate cocrystallization experiments. Various points in this region, representative of different compositions of Carbamazepine, Nicotinamide and CNC, were selected and spray drying was carried out. The spray dried product was characterized for solid state properties and was compared with CNC generated by liquid assisted grinding. Spray drying successfully generated CNC of similar quality as those generated by liquid assisted grinding. Moreover, there was no significant impact of process variables on formation of CNC. Spray drying, owing to its simplicity and industrial scalability, can be a promising method for large scale cocrystal generation.

  12. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    Directory of Open Access Journals (Sweden)

    Okujava Michael

    2001-11-01

    Full Text Available Abstract Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry influences the blood oxygenation level dependent (BOLD contrast changes induced by neuronal activation and measured by functional MRI (fMRI. We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE. Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

  13. Carbamazepine dose requirements during stiripentol therapy: influence of cytochrome P-450 inhibition by stiripentol.

    Science.gov (United States)

    Kerr, B M; Martinez-Lage, J M; Viteri, C; Tor, J; Eddy, A C; Levy, R H

    1991-01-01

    The inhibitory effect of stiripentol (STP) on disposition of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZE) was quantitated to establish CBZ dosage reduction guidelines for future clinical add-on efficacy trials of STP. In seven epileptic patients, STP (1,500-3,000 mg/day for 2 weeks) inhibited CBZ clearance by 50 +/- 16% (p = 0.001) and reduced the CBZE/CBZ plasma ratio by 45 +/- 14% (p = 0.0005). The inhibitory effect was gradually manifested over a period of 7-10 days after initiation of STP therapy. In contrast to inhibition of CBZE formation, STP had no effect (p greater than 0.05) on elimination clearance or half-life (t1/2) of CBZE in six healthy volunteers. STP most likely exerts inhibitory effects through inhibition of cytochrome P-450. This hypothesis was confirmed in the present study by the finding that a therapeutic concentration of STP (7 micrograms/mL) inhibited 10,11-epoxidation of CBZ in human liver microsomes by 40-50%. On the basis of results from this study, we propose that (a) CBZ dosage should be reduced in steps over a period of 7-10 days after initiation of STP, and (b) a CBZ dosage of 4.3 to 8.7 mg/kg/day will maintain therapeutic CBZ plasma levels of 5-10 micrograms/mL.

  14. 卡马西平致排尿困难%Dysuria induced by carbamazepine

    Institute of Scientific and Technical Information of China (English)

    孙健; 刘朋; 傅得兴; 刘治军

    2011-01-01

    A 75-year-old male patient with prostatic carcinoma received carbamazepine 0. 1 g twice daily for postherpetic neuralgia. Two days later, he experienced a weak urine stream, disabling frequent urination, and stuttering urination. Five days later,carbamazepine was increased to 0.2 g twice daily. His dysuria aggravated, and then his urine was drained using a urinary catheter.The drug was discontinued. The next day, the patient urinated himself and, on day 5, he recovered completely.%1例75岁男性前列腺癌患者,因带状疱疹后神经痛,服用卡马西平0.1 g,2次/d.2 d后,患者出现尿流变细、尿频无力和分段尿.5 d后,卡马西平增至0.2 g,2次/d,患者排尿困难加重,遂用导尿管排尿.停用该药,次日,患者自行排尿增多,第5天完全恢复正常.

  15. Formulation consideration and characterization of microemulsion drug delivery system for transnasal administration of carbamazepine

    Directory of Open Access Journals (Sweden)

    Rashmin B. Patel

    2013-12-01

    Full Text Available The purpose of the present study was to formulate and characterize carbamazepine loaded microemulsion and mucoadhesive microemulsion drug delivery system for its intranasal administration. Carbamazepine microemulsion and mucoadhesive microemulsion were prepared by titration method. The drug-loaded microemulsions were successfully prepared which contain 6% Labrafil M 1944 CS as an oily phase, 32% surfactant mixture of Cremophor RH 40: Transcutol P (4:1 and 62% (wt/wt aqueous phase. Microemulsion formulation which displayed an optical transparency of 99.95%, globule size of 34.32 ± 1.09 nm, and polydispersity index of 0.127 ± 0.012 was selected for the incorporation of mucoadhesive component. The drug-loaded mucoadhesive microemulsion that contains 0.5% wt/wt of polycarbophil displayed higher in vitro mucoadhesive potential (21.0 ± 3.0 min and diffusion coefficient (0.3172 ± 0.03 than microemulsion. All formulations were found free from nasal ciliotoxicity and stable for 6 months.

  16. Carbamazepine-induced upregulation of adenosine A(1)-receptors in astrocyte cultures affects coupling to the phosphoinositol signaling pathway

    NARCIS (Netherlands)

    Biber, K; Fiebich, BL; Gebicke-Harter, P; van Calker, D

    1999-01-01

    The anticonvulsant and antibipolar drug carbamazepine (CBZ) is known to act as a specific antagonist at adenosine A(1)-receptors. After a 3-week application of CBZ, A(1)-receptors are upregulated in the rat brain. We have investigated the consequences of this upregulation for the A(1)-receptor-media

  17. Fate of carbamazepine, its metabolites, and lamotrigine in soils irrigated with reclaimed wastewater: Sorption, leaching and plant uptake.

    Science.gov (United States)

    Paz, Anat; Tadmor, Galit; Malchi, Tomer; Blotevogel, Jens; Borch, Thomas; Polubesova, Tamara; Chefetz, Benny

    2016-10-01

    Irrigation with reclaimed wastewater may result in the ubiquitous presence of pharmaceutical compounds (PCs) and their metabolites in the agroecosystem. In this study, we focused on two highly persistent anticonvulsant drugs, lamotrigine and carbamazepine and two of its metabolites (EP-CBZ and DiOH-CBZ), aiming to elucidate their behavior in agricultural ecosystem using batch and lysimeter experiments. Sorption of the studied compounds by soils was found to be governed mainly by the soil organic matter level. Sorption affinity of compounds to soils followed the order lamotrigine > carbamazepine > EP-CBZ > DiOH-CBZ. Sorption was reversible, and no competition between sorbates in bi-solute systems was observed. The results of the lysimeter studies were in accordance with batch experiment findings, demonstrating accumulation of lamotrigine and carbamazepine in top soil layers enriched with organic matter. Detection of carbamazepine and one of its metabolites in rain-fed wheat previously irrigated with reclaimed wastewater, indicates reversibility of their sorption, resulting in their potential leaching and their availability for plant uptake. This study demonstrates the long-term implication of introduction of PCs to the agroecosystem.

  18. Kinetic changes and modulation by carbamazepine on voltage-gated sodium channels in rat CA1 neurons after epilepsy.

    NARCIS (Netherlands)

    G. Sun; T.R. Werkman; W.J. Wadman

    2006-01-01

    AIM: To study whether the functional properties of sodium channels, and subsequently the channel modulation by carbamazepine (CBZ) in hippocampal CA1 neurons can be changed after epileptic seizures. METHODS: We used the acutely dissociated hippocampal CA1 pyramidal cells from epilepsy model rats 3 w

  19. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4

    DEFF Research Database (Denmark)

    Andreasen, Astrid-Helene; Brøsen, Kim; Damkier, Per

    2007-01-01

    PURPOSE: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. ...

  20. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  1. Application of experimental design in examination of the dissolution rate of carbamazepine from formulations: Characterization of the optimal formulation by DSC, TGA, FT-IR and PXRD analysis

    Directory of Open Access Journals (Sweden)

    Krstić Marko

    2015-01-01

    Full Text Available Poor solubility is one of the key reasons for the poor bioavailability of these drugs. This paper displays a formulation of a solid surfactant system with carbamazepine, in order to increase its dissolution rate. Solid state surfactant systems are formed by application of fractal experimental design. Poloxamer 237 and Poloxamer 338 were used as surfactants and Brij® 35 was used as the co-surfactant. The ratios of the excipients and carbamazepine were varied and their effects on the dissolution rate of carbamazepine were examined. Moreover, the effects of the addition of natural (diatomite and a synthetic adsorbent carrier (Neusiline UFL2 on the dissolution rate of carbamazepine were also tested. The prepared surfactant systems were characterized and the influence of the excipients on possible changes of the polymorphous form of carbamazepine examined by application of analytical techniques (DSC, TGA, FT-IR, PXRD. It was determined that an appropriate selection of the excipient type and ratio could provide a significant increase in the carbamazepine dissolution rate. By application of analytical techniques, it was found that that the employed excipients induce a transition of carbamazepine into the amorphous form and that the selected sample was stable for three months, when kept under ambient conditions. [Projekat Ministarstva nauke Republike Srbije, br. TR34007

  2. CORRELATION OF THE SERUM LEVEL OF CARBAMAZEPINE WITH SEIZURE CONTROL AND ADVERSE DRUG REACTIONS AMONG EPILEPTICS IN IBADAN, NIGERIA

    Directory of Open Access Journals (Sweden)

    Joseph O. Fadare

    2010-12-01

    Full Text Available Background: Epilepsy is a chronic neurological disorder requiring long-term treatment. Seizure control requires adequate blood levels of anti-seizure drugs. Carbarmazepine is one of the most prescribed antiepileptic drugs in Nigeria. This study was carried out to investigate the correlation between serum levels of carbamazepine and seizure control and adverse drug reactions among epileptics in Ibadan, Nigeria. Methods: In a cross-sectional study, sixty-nine patients with confirmed diagnosis of epilepsy who had been on treatment with carbamazepine alone or in combination with phenytoin for at least one month were enrolled into the study and divided into two groups based on seizure control. Drug level in pre-dose (steady state venous blood was analyzed using high performance liquid chromatography. Result: The mean serum concentration of carbamazepine (CBZ and carbamazepine-epoxide (CBZ-EP was 13.5±9.3ìg/mL and 6.34±12.61ìg/mL respectively. Patients with good seizure control had mean serum CBZ concentration of 12.7 ± 9.2ìg/mL versus 15.02 ± 9.7ìg/mL among patients with poor seizure control (P=0.33. The serum concentration of CBZ-EP in patients with good seizure control was 8.05 ± 15.2ìg/mL while it was 3.11 ± 3.5ìg/mL in the second group (P=0.122. Drowsiness was the commonest adverse drug reaction (26.1% and it did not necessitate withdrawal of the drug. Conclusion The study showed that serum level of carbamazepine does not correlate with seizure control and adverse drug reactions.

  3. Drug-induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine.

    Science.gov (United States)

    Molina-Ruiz, Ana María; Lasanta, Begoña; Barcia, Ana; Pérez-Vega, Elisa; Requena, Luis

    2017-02-01

    Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.

  4. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae-Sung, E-mail: Jae.Kim@surgery.ufl.edu; Wang, Jin-Hee, E-mail: jin-hee.wang@surgery.ufl.edu; Biel, Thomas G., E-mail: Thomas.Biel@surgery.ufl.edu; Kim, Do-Sung, E-mail: do-sung.kim@surgery.med.ufl.edu; Flores-Toro, Joseph A., E-mail: Joseph.Flores-Toro@surgery.ufl.edu; Vijayvargiya, Richa, E-mail: rvijayvargiya@ufl.edu; Zendejas, Ivan, E-mail: ivan.zendejas@surgery.ufl.edu; Behrns, Kevin E., E-mail: Kevin.Behrns@surgery.ufl.edu

    2013-12-15

    Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R. - Highlights: • A mechanism of carbamazepine (CBZ)-induced cytoprotection in livers is proposed. • Impaired autophagy is a key event contributing to lethal reperfusion injury. • The importance of autophagy is extended and confirmed in an in vivo model. • CBZ is a potential

  5. Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature.

    Science.gov (United States)

    Parrish, Richard H; Pazdur, Danielle E; O'donnell, Philip J

    2006-11-01

    A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.

  6. Carbamazepine-induced hypersensitivity syndrome%卡马西平超敏综合征

    Institute of Scientific and Technical Information of China (English)

    王雪妮; 刘泽; 王伟; 王鲁妮

    2011-01-01

    A 59-year-old man developed a temporary skin rash on his lower limbs after taking carbamazepine 0.1 g 1-2 times daily for seven days for tinnitus. His rash disappeared after withdrawal of carbamazepine. Subsequently, he was hospitalised with worsening tinnitus and received oral carbamazepine 0. 1 g twice daily and oral mecobalamin 1 mg thrice daily. On day 2 of admission, his temperature was 39.2℃ and, on day 3, he presented with a red maculopapular rash on his face, body, and both knees. Biochemical blood tests revealed the following values; ALT 359 U/L, AST 137 U/L, γ-GT 506 U/L, and LDH 273 U/L. Carbamazepine and mecobalamin was stopped. Methylprednisolone and anti-allergic therapy were given. Two day later, his temperature normalized and, five days later, rash and hepatic function improved gradually. On day 9 of admission, the patient had a fever again with a temperature of 38.1 ℃. Later, his rash recurred and progressed to involve his entire body. Laboratory tests showed the following levels; WBC 13. 78 × 109/L with eosinophils 0.113, ALT 187 U/L, AST 45 U/L, γ-GT 374 U/L, and LDH 239 U/L. Carbamazepine-induced hypersensitivity syndrome was diagnosed. Methylprednisolone and human immune globulin were given and his rash and hepatic function improved. On day 16 of admission, the rash reappeared on his lower extremities, and then resolved after administration of methylprednisone and symptomatic treatment.%1例59岁男性患者因耳鸣服用卡马西平0.1g,1~2次/d,服药7d后出现双下肢一过性皮疹.停用卡马西平后皮疹消失,但随后耳鸣症状加重,遂入院,给予卡马西平0.1g,2次/d口服;甲钴胺1 mg,3次/d口服.入院第2天患者体温39.2℃;第3天面颊部、躯干及双侧膝关节处出现红色斑丘疹.血生化检查示丙氨酸转氨酶359 U/L,天冬氨酸转氨酶137 U/L,γ-谷氨酰转移酶506 U/L,乳酸脱氢酶273 U/L.停用卡马西平及甲钴胺,给予甲泼尼龙及抗过敏治疗.2d

  7. Pharmacodynamic and pharmacokinetic interaction of Panchagavya Ghrita with phenytoin and carbamazepine in maximal electroshock induced seizures in rats

    OpenAIRE

    Joshi, Rupa; Reeta, K.H.; Sharma, Surinder Kumar; Tripathi, Manjari; Gupta, Yogendra Kumar

    2015-01-01

    Introduction: Traditionally, Panchagavya Ghrita (PG) has been used for the management of epilepsy, anxiety, fever and jaundice. It consists of five components of cow products namely, cow milk, clarified butter from cow milk, cow urine, curd from cow milk, and cow dung juice. Aim: To evaluate the effect of PG in maximal electroshock (MES) induced seizures model and its pharmacodynamic and pharmacokinetic interaction with phenytoin (PHT) and carbamazepine (CBZ) in rats. Materials and Methods: M...

  8. Measured and predicted environmental concentrations of carbamazepine, diclofenac, and metoprolol in small and medium rivers in northern Germany.

    Science.gov (United States)

    Meyer, Wibke; Reich, Margrit; Beier, Silvio; Behrendt, Joachim; Gulyas, Holger; Otterpohl, Ralf

    2016-08-01

    This study evaluated the impact of secondary municipal effluent discharge on carbamazepine, diclofenac, and metoprolol concentrations in small and medium rivers in northern Germany and compared the measured environmental concentrations (MECs) to the predicted environmental concentrations (PECs) calculated with four well-established models. During a 1-year sampling period, secondary effluent grab samples were collected at four wastewater treatment plants (WWTPs) together with grab samples from the receiving waters upstream and downstream from the wastewater discharge points. The carbamazepine, diclofenac, and metoprolol concentrations were analyzed with high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS) after solid phase extraction. In the secondary effluents, 84-790 ng/L carbamazepine, 395-2100 ng/L diclofenac, and 745-5000 ng/L metoprolol were detected. The carbamazepine, diclofenac, and metoprolol concentrations analyzed in the rivers downstream from the secondary effluent discharge sites ranged from <5 to 68, 370, and 520 ng/L, respectively. Most of the downstream pharmaceutical concentrations were markedly higher than the corresponding upstream concentrations. The impact of wastewater discharge on the MECs in rivers downstream from the WWTPs was clearly demonstrated, but the correlations of the MECs with dilution factors were poor. The smallest rivers exhibited the largest maximum MECs and the widest ranges of MECs downstream from the wastewater discharge point. Three of the four tested models were conservative, as they showed higher PECs than the MECs in the rivers downstream from the WWTPs. However, the most detailed model underestimated the diclofenac concentrations.

  9. The use of quantum chemistry in pharmaceutical research as illustrated by case studies of indometacin and carbamazepine

    DEFF Research Database (Denmark)

    Gordon, Keith C; McGoverin, Cushla M; Strachan, Clare J

    2007-01-01

    A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed....... The use of calculated structures and molecular electrostatic potentials in developing quantitative structure-activity relationships is discussed along with the use of computation chemistry to predict spectroscopic properties....

  10. Solubility and dissolution enhancement of HPMC - based solid dispersions of carbamazepine by hot-melt extrusion technique

    OpenAIRE

    Sharadchandra Dagadu Javeer; Purnima Dhanraj Amin

    2014-01-01

    The objective of this study was to investigate solid dispersions (SDs) of poorly water soluble drug carbamazepine (CBZ), prepared using low viscosity grade hydroxypropyl methyl cellulose (HPMC) (Methocel® E3 LV and Methocel® E5 LV) by hot-melt extrusion (HME) technology. Saturation solubility and dissolution profile of CBZ was studied. Characterization of hot-melt extruded samples was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray di...

  11. Competitive sorption of atenolol, trimetoprim, carbamazepine and sulfamethoxazole in three soil types

    Science.gov (United States)

    Kočárek, Martin; Kodešová, Radka; Klement, Aleš; Golovko, Oksana; Fér, Miroslav; Nikodem, Antonín; Vondráčková, Lenka; Jakšík, Ondřej; Grabic, Roman

    2016-04-01

    Transport of human and veterinary pharmaceuticals in soils and consequent ground-water contamination are influenced by many factors, including compound sorption on soil particles and dissipation. Batch sorption experiment for 9 soils (3 soil types with 3 (Greyic Phaeozem on loess), 4 (Haplic Luvisol on loess) and 2 (Haplic Cambisol on gneiss) horizons) and mixture of 4 pharmaceuticals (atenolol, trimetoprim, carbamazepine and sulfamethoxazole) was performed to study competitive sorption of compounds in each soil sample. Sorption affinities and dissipation half-lives of all compounds in topsoils were previously studied by Kodešová et al. (2015 and 2016). Ten grams of dry soil was placed directly into the plastic centrifuge tubes and 20 ml of solution of a known pharmaceutical concentration was added. The same concentrations (0.5, 1, 2.5, 5 and 10 mg/l) were used for all compounds. Three replicates of each concentration were applied for each soil. Tube was shaken for 24 h using the shaking apparatus at 20 C. After shaking, the analyzed soil suspension was centrifuged for 10 min at 6,000 rotations per minute. The actual initial and final equilibrium pharmaceutical concentrations were measured using two-dimensional liquid chromatography-tandem mass spectrometry LC/LC-MS/MS using isotope dilution and internal standard methods. The pharmaceutical concentration adsorbed on soil particles was calculated using the initial and final (i.e. after incubation) pharmaceutical concentrations. The Freundlich equations were used to fit data points of the measured adsorption isotherms. In the case of carbamazepine (neutral form) and sulfamethoxazole (partly negatively charged) sorption affinity of compounds decrease with soil depth. On the other hand in the case of atenolol and trimethoprim (both positively charged) compound sorption affinity was not depth dependent. Data obtained for top soils were compared with sorption affinities for single compounds published by (Kodešová et

  12. A new herb–drug interaction of Polygonum cuspidatum, a resveratrol‐rich nutraceutical, with carbamazepine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Ying-Chang [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, 40402, Taiwan (China); Lin, Shiuan-Pey [School of Pharmacy, China Medical University, Taichung, 40402, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, 40402, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan (China)

    2012-09-15

    Carbamazepine (CBZ), an antiepileptic with narrow therapeutic window, is a substrate of CYP 3A which metabolizes CBZ to carbamazepine-10,11-epoxide (CBZE), an active metabolite. This study investigated the acute and chronic effects of Polygonum cuspidatum (PC), a resveratrol‐rich nutraceutical, on the pharmacokinetics of CBZ in rats and the underlying mechanisms. Rats were orally administered CBZ (200 mg/kg) alone and coadministered with a single dose and the 7th dose of PC (2 g/kg) in a crossover design. The concentrations of CBZ and CBZE in serum and various tissues were determined by HPLC method. The results showed that PC significantly increased the AUC{sub 0-t} of CBZ and CBZE, whereas the formation rate of CBZE was decreased. Tissue analysis showed that the concentrations of CBZ and CBZE in brain, liver and kidney were significantly increased by PC. Cell studies indicated that the efflux function of MRP 2 was inhibited by the serum metabolites of PC. In conclusion, PC markedly increased the systemic exposure and brain concentration of CBZ and CBZE through inhibiting the activities of CYP 3A and MRP 2. Highlights: ► Polygonum cuspidatum elevated brain carbamazepine (CBZ) levels. ► Polygonum cuspidatum inhibited the activities of CYP 3A and MRP 2. ► Coadministration of PC with CBZ may enhance efficacy or toxicity.

  13. Degradation of the endocrine disrupting chemicals (EDCs) carbamazepine, clofibric acid, and iopromide by corona discharge over water.

    Science.gov (United States)

    Krause, Holger; Schweiger, Bianca; Schuhmacher, Jörg; Scholl, Saskia; Steinfeld, Ute

    2009-04-01

    Common wastewater treatment plants often do not eliminate endocrine disrupting chemicals (EDCs). Aqueous solutions of three EDCs were treated with an enhanced corona discharge technology. The three EDCs were clofibric acid, a blood lipid regulator, carbamazepine, an antiepileptic drug, and iopromide, a contrast media. To simulate real conditions, EDC solutions containing landfill leachate were also used. In our setup, two barrier electrodes provided an atmospheric pressure corona discharge over a thin water film, in which the counter-electrode was submerged. Clofibric acid, carbamazepine, and iopromide were effectively removed from a single solution. After a treatment of 15min, there were no traces of iopromide estrogen activity either as a single substance or as degradation products when using an E-Screen Assay. Continuous treatment was compared with pulsed treatment using carbamazepine solutions mixed with pretreated landfill leachate. Best degradation results were achieved with a 500 W continuous duty cycle treatment. Counter-electrodes from materials such as boron doped diamond (BDD), titanium iridium oxide, and iron were investigated for their influences on the process effectivity. Significant improvements were achieved by using an enclosed reactor, BDD electrodes, and circulating only a fresh air or argon/air mixture as cooling gas through the barrier electrodes.

  14. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review

    Science.gov (United States)

    EL Omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug. PMID:25360193

  15. Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) induced by carbamazepine: a case report and literature review.

    Science.gov (United States)

    E L omairi, Nissrine; Abourazzak, Sanae; Chaouki, Sanae; Atmani, Samir; Hida, Moustapha

    2014-01-01

    Drug-induced hypersensitivity or Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) is a severe adverse drug-induced reaction. Diagnosing DRESS is challenging due to the diversity of cutaneous eruption and organs involved. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital, and carbamazepine, can induce DRESS. Culprit drug withdrawal and corticosteroids constituted the mainstay of DRESS treatment. We describe a 6 year-old boy who presented fever and rash 4 weeks after starting carbamazepine. Investigation revealed leukocytosis, atypical lymphocytosis, and elevated serum transaminases. The diagnosis of DREES syndrome was made, Carbamazepine was stopped and replaced initially by Clobazam and by Valproic acid after discharge, no systemic corticotherapy was prescribed. Symptoms began to resolve within two weeks, and by one month later her laboratory values had returned to normal. The aim of this work is to raise awareness general practitioner and pediatricians to suspect Dress syndrome in patients who present with unusual complaints and skin findings after starting any antiepileptic drug.

  16. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine

    Directory of Open Access Journals (Sweden)

    Krstić Marko Z.

    2016-01-01

    Full Text Available One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS. Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS consisting of oil phase (caprilic-capric triglycerides, a surfactant (Polisorbat 80 and Labrasol® (1:1 and cosurfactant (Transcutol® HP are formed by applying mixture design. 16 formulations were formulated, where proportion of lipids, surfactant and cosurfactant were varied (input parameters in the following ranges: 10-30%, 40-60%, 30-50%, respectively. After dilution of SEDDS with water (90% water, the droplet size and polydispersity index (PdI of the obtained emulsions (output parameters were measured using photon correlation spectroscopy. After processing data, appropriate mathematical models that describe the dependence of input and output parameters were selected. The optimized SNEDDS was adsorbed on the carbamazepine and solid carrier physical mixture, containing 20% carbamazepine. Neusilin® UFl2, Neusilin® FL2, Sylysia® 320, diatomite were used as the carriers. The ratio of SNEDDS:carrier varied (1:1, 2:1. Dissolution testing was carried out in the rotation paddles apparatus. Caracterization of solid SNEDDS was performed using the hot stage microscopy (HSM, thermogravimetric analysis (TGA, differential scanning calorimetry (DSC, infrared spectrophotometry with Fourier transformation (FT-IR, scanning electron microscopy (SEM and X-ray diffraction (PXRD. Selected SNEDDS consisting of lipids (21.12%, surfactant (42.24% and cosurfactant (36.64% had a droplet size 157.02±34.09 nm and PDI 0.184±0.021. Drug release profiles showed that in all formulations dissolution rate increased (the fastest drug release was observed in formulations with Sylysia® 320. It can be concluded that in all

  17. Carbamazepine-Fumaric Acid Co-Crystal Screening Using Solution Based Method

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    Abd Rahim Syarifah

    2016-01-01

    Full Text Available Co-crystals is a multi-component system which connected by non-covalent interactions, present physically as a solid form under ambient conditions. Nowadays, co-crystal has becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ and fumaric acid (FUM co-crystal former (CCF using non-stoichiometric method (addition of CBZ to CCF saturated solution and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD, Differential Scanning Calorimetry (DSC and Fourier Transform Infrared (FT-IR. The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method where no crystal was found precipitate. The findings from this study revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvent systems.

  18. Recrystallization of Commercial Carbamazepine Samples—A Strategy to Control Dissolution Variability

    Directory of Open Access Journals (Sweden)

    Felicia Flicker

    2012-01-01

    Full Text Available Physical properties of commercial carbamazepine (CBZ samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were recrystallized in ethanol solution containing 1% polyvinylpyrrolidone (PVP. CBZ samples were analyzed by disk intrinsic dissolution rate (DIDR, X-ray powder diffraction (XRPD, differential scanning calorimetry (DSC, and scanning electron microscopy (SEM. Recrystallized CBZ samples showed strongly reduced variability in DIDR compared to the untreated CBZ samples. Moreover, transformation process to CBZ dihydrate was inhibited; no dihydrate crystals were visible on compact surfaces after 8 h intrinsic dissolution measurement. Recrystallized CBZ samples showed no change in polymorphic form, however, particle size and shape was inhomogenous. In binary mixtures with microcrystalline cellulose, recrystallized CBZ samples again showed difference in drug release. This difference was associated with the inhomogenous particle size in the recrystallized CBZ samples. The results show that a controlled grinding step is required after recrystallization. We suggest the recrystallization in presence of 1% PVP followed by a controlled grinding step as a strategy to reduce dissolution variability in commercial CBZ samples.

  19. Assessment of the effects of the carbamazepine on the endogenous endocrine system of Daphnia magna.

    Science.gov (United States)

    Oropesa, A L; Floro, A M; Palma, P

    2016-09-01

    In the present study, the endocrine activity of the antiepileptic pharmaceutical carbamazepine (CBZ) in the crustacean Daphnia magna was assessed. To assess the hormonal activity of the drug, we exposed maternal daphnids and embryos to environmental relevant concentrations of CBZ (ranging from 10 to 200 μg/L) and to mixtures of CBZ with fenoxycarb (FEN; 1 μg/L). Chronic exposure to CBZ significantly decreased the reproductive output and the number of molts of D. magna at 200 μg/L. This compound induced the production of male offspring (12 ± 1.7 %), in a non-concentration-dependent manner, acting as a weak juvenile hormone analog. Results showed that this substance, at tested concentrations, did not antagonize the juvenoid action of FEN. Further, CBZ has shown to be toxic to daphnid embryos through maternal exposure interfering with their normal gastrulation and organogenesis stages but not producing direct embryo toxicity. These findings suggest that CBZ could act as an endocrine disruptor in D. magna as it decreases the reproductive output, interferes with sex determination, and causes development abnormality in offspring. Therefore, CBZ could directly affect the population sustainability.

  20. The teratogenic effect of carbamazepine: a meta-analysis of 1255 exposures.

    Science.gov (United States)

    Matalon, S; Schechtman, S; Goldzweig, G; Ornoy, A

    2002-01-01

    Maternal use of antiepileptic drugs during pregnancy has been associated with an increased risk of major congenital abnormalities in the fetus. Carbamazepine (CBZ) is an antiepileptic drug that was developed and marketed mainly for the treatment of epileptic seizures. Some investigators described an increased rate of major congenital anomalies following treatment with CBZ during pregnancy while others found no such increase. In order to quantify better the risks of exposure to CBZ during pregnancy, we pooled data from prospective studies known to us. We found in prospective studies involving 1255 cases of exposure that CBZ therapy increased the rate of congenital anomalies, mainly neural tube defects, cardiovascular and urinary tract anomalies, and cleft palate. CBZ may also induce a pattern of minor congenital anomalies and developmental retardation, but our study did not address these endpoints. CBZ also appears to reduce gestational age at delivery. A combination of CBZ with other antiepileptic drugs is more teratogenic than CBZ monotherapy. Children born to untreated epileptic women do not appear to have an increased rate of major birth defects. In light of these results, we recommend performing a level 2 ultrasound and fetal echocardiography in women treated with CBZ during pregnancy.

  1. Biopharmaceutical constants for carbamazepine immediate release tablets in simplifying bioequivalence studies

    Directory of Open Access Journals (Sweden)

    Nanayakkara Mangala

    2006-01-01

    Full Text Available Current study was undertaken in order to determine model biopharmaceutical constants for carbamazepine immediate release tablets (200 mg from documented data of plasma concentration vs time curves. The constants and the proposed methodology simplify bioequivalence determinations to blood sampling restricted only to two time points. Twelve volunteer drug plasma concentration (Cp determinations from a crossover design bioequivalence study were fitted into equations containing two rate processes. The optimized rate constants were used to generate the Cp vs time curves (generated curves. Generated curves were then differentiated (dCp/dt to obtain the first derivative curve for each volunteer from which times for highest rate of absorption (TAmaxn and highest rate of elimination (TEmaxn were determined. The corresponding highest rate of absorption and the highest rate of elimination for each individual were then obtained from the generated curve and named as Amaxn and Emaxn. Individual Amaxn and Emaxn values were then averaged to obtain the mean Amax and Emax. Out of the 24 determinations, a total of 13 Amaxn and 20 Emaxn values fell within ±20% of the overall mean. Final Amax and Emax values ware arrived at by averaging each set of individual 13 values and 20 values respectively. From these two mean coordinates, the corresponding constants, plasma drug concentration at the point of highest rate of absorption (CpAmax and corresponding time TAmax, as well as the plasma drug concentration at the point of highest rate of elimination (CpEmax and the corresponding time TEmax, were determined.

  2. Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study.

    Science.gov (United States)

    Patel, Rashmin Bharatbhai; Patel, Mrunali Rashmin; Bhatt, Kashyap K; Patel, Bharat G; Gaikwad, Rajiv V

    2016-01-01

    This study reports the development and evaluation of Carbamazepine (CMP)-loaded microemulsions (CMPME) for intranasal delivery in the treatment of epilepsy. The CMPME was prepared by the spontaneous emulsification method and characterized for physicochemical parameters. All formulations were radiolabeled with (99m)Tc (technetium) and biodistribution of CMP in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rats was also performed to determine the uptake of the CMP into the brain. CMPME were found crystal clear and stable with average globule size of 34.11 ± 1.41 nm. (99m)Tc-labeled CMP solution (CMPS)/CMPME/CMP mucoadhesive microemulsion (CMPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMPMME compared to intravenous CMPME was found to be 2- to 3-fold higher signifying larger extent of distribution of the CMP in brain. Drug targeting efficiency and direct drug transport were found to be highest for CMPMME post-intranasal administration compared to intravenous CMP. Rat brain scintigraphy also demonstrated higher intranasal uptake of the CMP into the brain. This investigation demonstrates a prompt and larger extent of transport of CMP into the brain through intranasal CMPMME, which may prove beneficial for treatment of epilepsy.

  3. Protective effect of aqueous jujube extract in Carbamazepine induced teratogenicity on Balb/c mice fetuses

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    Doostabadi Mohammadreza

    2016-06-01

    Full Text Available Aim: Carbamazepine (CBZ is an anticonvulsant medication that can produce congenital anomalies. This study aimed to assess protective role of aqueous jujube extract (JE on CBZ induced congenital anomalies in mice fetuses. Methods:One hundred pregnant Balb/c mice were divided into 8 experimental (E and 2 control (C groups equally. The groups (E1, E5, E6 and (E2, E7, E8 received 50 and 100 mg/kg of CBZ, respectively IP, from GD 0 to GD15. Besides, groups (E5, E7 and (E6, E8 in addition to CBZ, were treated with 200 and 400 mg/kg JE, respectively from ten days prior to gestation, till GD15. The groups E3 and E4 received only 200 and 400 mg/kg of JE respectively. The control groups (C1, C2 received normal saline and tween-20 in turn. On GD18 dams cesarianed and their fetuses assessed for skeletal anomalies by using Alizarin red-alcian blue staining. Results:CBZ induced various anomalies such as; limb defects, craniofacial malformations and etc in mice fetuses. However, these anomalies significantly decreased in groups which were co-administered with CBZ and JE. Conclusion: Co-administration of JE and CBZ significantly decrease teratogenicity of CBZ. Therefore, JE may play a protective role against those properties of CBZ inducing teratogenicity

  4. Transport of carbamazepine and drug interactions at blood-brain barrier

    Institute of Scientific and Technical Information of China (English)

    Jing-jing SUN; Lin XIE; Xiao-dong LIU

    2006-01-01

    Aim: To investigate the characteristics of carbamazepine (CBZ) transport and drug interactions at the blood-brain barrier. Methods: Cultured rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). When cells became confluent, CBZ uptake over time was recorded by incubation of the cells in a medium containing 10 mg/L CBZ at 37 ℃. The steady-state uptake of CBZ by rBMEC was tested for different CBZ concentrations at 37 ℃. The effects of various agents on the steady-state uptake of CBZ and efflux of CBZ from rBMEC were also studied. Results: The uptake of CBZ by rBMEC was time- and concentration-dependent. The steady-state uptake occurred at 30 min for incubation. The steady-state uptake was significantly increased (P<0.01) by treatment with dinitrophenol. The co-administration of cyclosporine A significantly increased the steady-state uptake of CBZ by the rBMEC, whereas co-administration of olanzapine significantly decreased the uptake in a concentration- and temperature-dependent manner. The efflux of CBZ from rBMEC was inhibited by CsA. Conclusion: The transport of CBZ at the BBB is mediated by many transporters. Some specific ABC (ATP-binding cassette,ABC ) efflux transporters may be involved in the transport of CBZ. Drugs influence the transport of CBZ at the BBB in different ways.

  5. [Fixed pigmented erythema related to the oral administration of carbamazepine: report of one case].

    Science.gov (United States)

    Alvarez, Verónica J; Picón, Jesús E; Morales, Alexis R; Goncalves, Edith T; Luna, José Rafael

    2006-03-01

    Carbamazepine (CBZ) is an oral anticonvulsant drug, structurally similar to tricyclic antidepressants. It is preferred over other drugs because it has fewer adverse effects on behavior and alertness. However, hematologic toxicity is possible during therapy with CBZ. Patients should undergo routine monitoring of hematologic function. CBZ can make the skin more sensitive to the sun or ultraviolet light, therefore, dermatological effects of this drug also can happen such as, skin rash, urticaria, and erythema multiforme. The present study reports the case of a female patient that presented hyperchromic-concentric-pruriginous- spots on the skin of her hands after six months of treatment with CBZ. She came to the physicians of the Clinical Pharmacokinetic Service (Laboratory of Toxicology of IAHULA, Mérida-Venezuela) requesting a drug monitoring. The results showed a level of 8.51 microg x. mL(-1), which was found within the therapeutic range (4-12 microg x mL(-1)). Subsequently, the dermatologist diagnosed fixed pigmented erythema related to the ingestion of a specific medication which began disappearing after 15 days of CBZ free-treatment and with the aid of a dermatologic formulation.

  6. Recrystallization of commercial carbamazepine samples-a strategy to control dissolution variability.

    Science.gov (United States)

    Flicker, Felicia; Eberle, Veronika A; Betz, Gabriele

    2012-01-13

    Physical properties of commercial carbamazepine (CBZ) samples can significantly influence drug release and thereby jeopardize bioequivalence of the final dosage form. The aim of this study was to reduce variability in commercial CBZ samples by recrystallization. CBZ samples of four different suppliers were recrystallized in ethanol solution containing 1% polyvinylpyrrolidone (PVP). CBZ samples were analyzed by disk intrinsic dissolution rate (DIDR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Recrystallized CBZ samples showed strongly reduced variability in DIDR compared to the untreated CBZ samples. Moreover, transformation process to CBZ dihydrate was inhibited; no dihydrate crystals were visible on compact surfaces after 8 h intrinsic dissolution measurement. Recrystallized CBZ samples showed no change in polymorphic form, however, particle size and shape was inhomogenous. In binary mixtures with microcrystalline cellulose, recrystallized CBZ samples again showed difference in drug release. This difference was associated with the inhomogenous particle size in the recrystallized CBZ samples. The results show that a controlled grinding step is required after recrystallization. We suggest the recrystallization in presence of 1% PVP followed by a controlled grinding step as a strategy to reduce dissolution variability in commercial CBZ samples.

  7. Magnetic cobalt ferrite composite as an efficient catalyst for photocatalytic oxidation of carbamazepine.

    Science.gov (United States)

    He, Yongzhen; Dai, Chaomeng; Zhou, Xuefei

    2017-01-01

    A magnetic spinel cobalt ferrite nanoparticle composite (CFO) was prepared via an ultrasonication-assisted co-precipitation method. The morphological structure and surface composition of CFO before and after reaction were investigated by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray, and Fourier transform infrared spectroscopy, indicating the consumption of iron oxide during photodegradation. X-ray photoelectron spectroscopy and vibrating sample magnetometry confirm the preparation of the ferrite nanoparticle composite and its magnetic properties. The prepared CFO was then used for the photocatalytic degradation of carbamazepine (CBZ) as an example of pharmaceuticals and personal care products (PPCPs) from aqueous solution. The effects of the nanocomposite dosage, contact time, and solution pH on the photodegradation process were investigated. More than 96% of the CBZ was degraded within 100 min at 0.2 g·L(-1) CFO in the presence of UV light. The reactive species for CBZ degradation in the CFO/UV system was identified as hydroxyl radicals by the methanol scavenging method. Combined with the detection of leached iron ions during the process, the CBZ degradation mechanism can be presumed to be heterogeneous and homogeneous photocatalytic degradation in the CFO/UV system. Furthermore, iminostilbene and acridine were detected as intermediate products by GC-MS.

  8. Severe Carbamazepine Intoxication in Children: Analysis of a 40-Case Series

    Science.gov (United States)

    Acikgoz, Mehmet; Paksu, M. Sukru; Guzel, Ahmet; Alacam, Abdurrahman; Alacam, Fatma

    2016-01-01

    Background We compared the factors that might impact the severity and the prognosis of carbamazepine (CBZ) intoxication in children, as well as the efficacy levels of the treatment options. Material/Methods Demographic information and clinical and laboratory findings for 40 patients were evaluated retrospectively. Predictive parameters for the development of serious complications were studied. Results Median age of patients was 14 years; 65% of the patients were female. The most common pathological clinical finding and laboratory abnormality were inability to awaken the patient and hyperglycemia (45% and 60%, respectively). The incidences of convulsion, coma, and respiratory failure were 14 (35%), 10 (25%), and 3 (7.5%), respectively. The Glasgow Coma Scale (GCS) scores and pH levels at emergency service admission were significantly lower in the severe intoxication group and the ICU admission group, and body temperature and serum glucose and lactate levels were significantly higher in these groups. A significantly negative correlation was found between the serum CBZ level and the GCS score, but the serum CBZ level was found to be significantly positively correlated with the lactate level. Conclusions According to our study, the GCS score at admission to hospital, the serum CBZ, glucose, pH, and lactate levels, and body temperature might be useful in predicting serious CBZ intoxication and prognosis in pediatric cases. We conclude that invasive treatment methods, such as hemodialysis or albumin-enhanced continuous venovenous hemodialysis, should be used in patients who do not respond to supportive treatment. PMID:27911891

  9. Simple and accurate measurement of carbamazepine in surface water by use of porous membrane-protected micro-solid-phase extraction coupled with isotope dilution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Hui Ling [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore); Wong, Lingkai [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Liu, Qinde, E-mail: liu_qinde@hsa.gov.sg [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Teo, Tang Lin; Lee, Tong Kooi [Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, 1 Science Park Road, #01-05/06, The Capricorn, Singapore Science Park II, Singapore 117528 (Singapore); Lee, Hian Kee, E-mail: chmleehk@nus.edu.sg [Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore)

    2016-03-17

    To achieve fast and accurate analysis of carbamazepine in surface water, we developed a novel porous membrane-protected micro-solid-phase extraction (μ-SPE) method, followed by liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) analysis. The μ-SPE device (∼0.8 × 1 cm) was fabricated by heat-sealing edges of a polypropylene membrane sheet to devise a bag enclosing the sorbent. The analytes (both carbamazepine and isotope-labelled carbamazepine) were first extracted by μ-SPE device in the sample (10 mL) via agitation, then desorbed in an organic solvent (1 mL) via ultrasonication. Several parameters such as organic solvent for pre-conditioning of μ-SPE device, amount of sorbent, adsorption time, and desorption solvent and time were investigated to optimize the μ-SPE efficiency. The optimized method has limits of detection and quantitation estimated to be 0.5 ng L{sup −1} and 1.6 ng L{sup −1}, respectively. Surface water samples spiked with different amounts of carbamazepine (close to 20, 500, and 1600 ng L{sup −1}, respectively) were analysed for the validation of method precision and accuracy. Good precision was obtained as demonstrated by relative standard deviations of 0.7% for the samples with concentrations of 500 and 1600 ng kg{sup −1}, and 5.8% for the sample with concentration of 20 ng kg{sup −1}. Good accuracy was also demonstrated by the relative recoveries in the range of 96.7%–103.5% for all samples with uncertainties of 1.1%–5.4%. Owing to the same chemical properties of carbamazepine and isotope-labelled carbamazepine, the isotope ratio in the μ-SPE procedure was accurately controlled. The use of μ-SPE coupled with IDMS analysis significantly facilitated the fast and accurate measurement of carbamazepine in surface water. - Highlights: • μ-SPE coupled with IDMS for the measurement of carbamazepine. • The method is the first report of coupling μ-SPE with IDMS. • μ-SPE is fast, time

  10. Transformation products and reaction pathways of carbamazepine during photocatalytic and sonophotocatalytic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jelic, A. [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Michael, I.; Achilleos, A.; Hapeshi, E. [Department of Civil and Environmental Engineering, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Nireas, International Water Research Centre, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Lambropoulou, D. [Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Perez, S., E-mail: spsqam@idaea.csic.es [Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Petrovic, M. [Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona (Spain); Fatta-Kassinos, D. [Department of Civil and Environmental Engineering, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Nireas, International Water Research Centre, University of Cyprus, 1 Panepistimiou Avenue, P.O. Box 20537, 1678 Nicosia (Cyprus); Barcelo, D. [Catalan Institute for Water Research (ICRA), H2O Building, Scientific and Technological Park of the University of Girona, 101-E-17003 Girona (Spain); Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluis Companys 23, 08010 Barcelona (Spain)

    2013-12-15

    Highlights: • Degradation of CBZ during US, TiO{sub 2}/UV and TiO{sub 2}/UV/US processes has been evaluated. • The combined TiO{sub 2}/UV/US oxidation resulted in significant enhancement of the CBZ degradation rate. • Transformation products were identified and the transformation pathways were proposed. • An acute toxicity test showed an increase in toxicity over the time-course of the studied processes. -- Abstract: This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO{sub 2}-based heterogeneous photocatalysis under UV-A and simulated solar irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e. sonophotocatalysis) in demineralized water, ground water and effluent wastewater. The processes were compared with respect to substrate conversion rate and the extent of DOC reduction as a measure of mineralization. CBZ was degraded following a pseudo-first order kinetics. Sonophotocatalysis provided the highest rate of CBZ transformation over the time-course of the experiment while the degree of DOC removal in pure water was similar for all the studied treatments (around 40%), and always lower than CBZ conversion. This indicated that a considerable organic load remained in the treated solutions that could also be attributed to the presence of persistent oxidation products. UPLC–(+ESI)-QToF-MS was employed to determine major CBZ-related transformation products. Several recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A Daphnia magna bioassay was used to evaluate the potential toxicity of the samples collected at different time points showing that the mixtures were highly toxic to D. magna.

  11. The HLA-A*31:01 allele: influence on carbamazepine treatment

    Science.gov (United States)

    Yip, Vincent Lai Ming; Pirmohamed, Munir

    2017-01-01

    Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening for HLA-B*15:02 is mandated in patients from South East Asia because of a strong association with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). HLA-A*31:01 predisposes to multiple phenotypes of CBZ hypersensitivity including maculopapular exanthema, hypersensitivity syndrome, and SJS/TEN in a range of populations including Europeans, Japanese, South Koreans and Han Chinese, although the effect size varies between the different phenotypes and populations. Between 47 Caucasians and 67 Japanese patients would need to be tested for HLA-A*31:01 in order to avoid a single case of CBZ hypersensitivity. A cost-effectiveness study has demonstrated that HLA-A*31:01 screening would be cost-effective. Patient preference assessment has also revealed that patients prefer pharmacogenetic screening and prescription of alternative anticonvulsants compared to current standard of practice without pharmacogenetic testing. For patients who test positive for HLA-A*31:01, alternative treatments are available. When alternatives have failed or are unavailable, HLA-A*31:01 testing can alert clinicians to 1) patients who are at increased risk of CBZ hypersensitivity who can then be targeted for more intensive monitoring and 2) increase diagnostic certainty in cases where hypersensitivity has already occurred, so patients can be advised to avoid structurally related drugs in the future. On the basis of the current evidence, we would favor screening all patients for HLA-A*31:01 and HLA-B*15:02 prior to starting CBZ therapy. PMID:28203102

  12. Fate and transport of carbamazepine in soil aquifer treatment (SAT) infiltration basin soils.

    Science.gov (United States)

    Arye, Gilboa; Dror, Ishai; Berkowitz, Brian

    2011-01-01

    The transport and fate of the pharmaceutical carbamazepine (CBZ) were investigated in the Dan Region Reclamation Project (SHAFDAN), Tel-Aviv, Israel. Soil samples were taken from seven subsections of soil profiles (150 cm) in infiltration basins of a soil aquifer treatment (SAT) system. The transport characteristics were studied from the release dynamics of soil-resident CBZ and, subsequently, from applying a pulse input of wastewater containing CBZ. In addition, a monitoring study was performed to evaluate the fate of CBZ after the SAT. Results of this study indicate adsorption, and consequently retardation, in CBZ transport through the top soil layer (0-5 cm) and to a lesser extent in the second layer (5-25 cm), but not in deeper soil layers (25-150 cm). The soluble and adsorbed fractions of CBZ obtained from the two upper soil layers comprised 45% of the total CBZ content in the entire soil profile. This behavior correlated to the higher organic matter content observed in the upper soil layers (0-25 cm). It is therefore deduced that when accounting for the full flow path of CBZ through the vadose zone to the groundwater region, the overall transport of CBZ in the SAT system is essentially conservative. The monitoring study revealed that the average concentration of CBZ decreased from 1094 ± 166 ng L⁻¹ in the recharged wastewater to 560 ± 175 ng L⁻¹ after the SAT. This reduction is explained by dilution of the recharged wastewater with resident groundwater, which may occur as it flows to active reclamation wells.

  13. Evaluating the Effectiveness of GTM-1, Rapamycin, and Carbamazepine on Autophagy and Alzheimer Disease

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    Zhang, Lijuan; Wang, Lina; Wang, Run; Gao, Yuan; Che, Haoyue; Pan, Yonghua; Fu, Peng

    2017-01-01

    Background This study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study. Material/Methods Firstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze. Routine blood tests were performed to evaluate the toxicity of these drugs. Amyloid-β42 (Aβ42) concentration was detected by ELISA and immunohistochemistry. Proteins related to autophagy were detected by Western blot. Results GTM-1, Rap, and CBZ significantly improved the spatial memory of 3×Tg AD mice compared to that in the vehicle group (all P<0.05). Moreover, this study revealed that CBZ dosage was related to toxicity in mice. All of the above drugs significantly increased the expression of LC3-II and reduced Aβ42 levels in hippocampi of 3×Tg AD mice (all P<0.05). On the other hand, neither GTM-1 nor CBZ had significant influence on the expression of proteins on the mTOR pathway. Conclusions GTM-1 can alleviate the AD syndrome by activating autophagy in a manner that is dependent on the mTOR pathway and it therefore can be considered as an alternative to Rap. PMID:28193995

  14. Effects of sodium valproate and carbamazepine on food competition aggression in pigeons

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    C. Fachinelli

    2007-06-01

    Full Text Available Valproate and carbamazepine (CAR have been proposed as adjunct alternatives for the control of aggression in psychiatric patients, although no definite conclusions have been reached. We examined the effects of these drugs on food competition offensive aggression and other behaviors in high- and low-aggression food-restricted pigeons. These were divided into pairs containing previously ranked high-aggression (N = 10 pairs and low-aggression females (N = 10 pairs. In Experiment 1, a pigeon in each pair of high- and low-aggression subjects was treated daily with an oral dose of sodium valproate (50 mg kg-1 mL saline-1 for 15 days. The other animal received the vehicle. On days 1, 7, and 15, food competition trials (10 min were performed 60 min after treatment. In Experiment 2, one pigeon in each pair was treated daily with an oral dose of CAR (20 mg kg-1 mL saline-1 for 15 days. Each pair was submitted to a food competition trial on days 1, 7, and 15 of treatment. Valproate (15 days of treatment selectively decreased the time spent in offensive aggression (control: 102.7 ± 9.3 vs valproate: 32.7 ± 9.2 s; P < 0.001, ANOVA-2-TAU of high-aggression pigeons. This was also the case for 7 and 15 days of CAR treatment (control: 131.5 ± 8.9 vs CAR: 60.4 ± 5.3, P < 0.01, and control: 122.7 ± 7.1 vs CAR: 39.1 ± 5.2; P < 0.001, ANOVA-2-TAU, respectively. Thus, the two anticonvulsive drugs have a similar effect on food competition aggression in pigeons.

  15. Effect of treatment with phenobarbital and stiripentol on carbamazepine-induced teratogenicity and reactive metabolite formation.

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    Finnell, R H; Bennett, G D; Slattery, J T; Amore, B M; Bajpai, M; Levy, R H

    1995-12-01

    A model using SWV mice was developed to investigate the mechanistic basis of carbamazepine (CBZ)-related fetotoxicity. Drug administration was initiated prior to conception and continued until day 18 of gestation. The incidence of malformation was 33% following CBZ exposure (1,500 mg/kg/day), compared with a 5% incidence in pair-fed control animals (P stiripentol (STP; a cytochrome P-450 inhibitor) (300 mg/kg/day) decreased the incidence of malformations produced by CBZ (1,500 mg/kg/day) from 33% to 16.7% (P < 0.05). The effect of PB administration on the binding of 14C in maternal and fetal tissue was assessed in dams that received CBZ (1,000 mg/kg/day) with or without PB (45 mg/kg/day) or STP (300 mg/kg/day) chronically and a single i.p. dose of 14C-CBZ on day 12 of gestation. In all instances, binding was greatest in maternal liver, then in the placenta, fetal head and body, and maternal thigh muscle. In all tissues, PB caused a two-to threefold increase in binding, compared with binding in mice exposed to CBZ alone. STP administration decreased protein adduct formation only in maternal liver. The binding of 14C was also assessed in hepatic microsomes prepared from female mice exposed to CBZ and PB or STP as in the in vivo study of 14C binding. The extent of irreversible binding was 67% greater in microsomes prepared from mice pretreated with PB and CBZ than with CBZ alone, while STP resulted in only 21% inhibition of 14C adduct formation (P < 0.05). The results are consistent with the formation of a chemically reactive teratogenic metabolite of CBZ in mice by cytochrome(s) P-450.

  16. Preventive Effect of Vitamin B6 on Developmental Toxicity of Carbamazepine in Mice

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    Mohammad Afshar

    2011-03-01

    Full Text Available Objective(sCarbamazepine (CBZ is an antiepileptic drug that is used widely for the treatment of epileptic seizures. Neural tube defects (NTDs, growth retardation, and nail hypoplasia are the most common features of teratogenic effects of this drug. The purpose of this study was to examine the effect of vitamin B6 on the developmental toxicity of CBZ on mice.Materials and MethodsSixty BALB/c pregnant mice were divided into four experimental and two control groups. Two experimental groups received daily intraperitoneal injection (IP of 30 mg/kg (I or 60 mg/kg (II of CBZ on gestational days (GD 6 to 15. Two other experimental groups received daily IP injection of 30 mg/kg (III or 60 mg/kg (IV of CBZ with 10 mg/kg/day vitamin B6 by gavage 10 days prior to gestation and on GD 6 to 15. Two control groups received normal saline or Tween 20. Dams underwent Cesarean section on GD 18 and embryos were harvested. External/macroscopic observation of fetuses was done by stereomicroscope and external examination for malformations was recorded. Data analyzed by ANOVA and X2 test using SPSS software.ResultsThe mean weight and crown-rump of the fetuses in both CBZ-treated experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, eye malformations, NTDs, vertebral deformity, brachydactyly and growth retardation. Vitamin B6 treatment significantly reduced various CBZ-induced malformations.ConclusionThis study showed that vitamin B6 has a preventive effect on the developmental toxicity of CBZ in mice that can be pursued further for clinical research.

  17. Carbamazepine, but not valproate, displays pharmacoresistance in lamotrigine-resistant amygdala kindled rats.

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    Srivastava, Ajay K; White, H Steve

    2013-03-01

    The voltage gated sodium channel (VGSC) blocker lamotrigine (LTG), when administered during kindling acquisition, leads to the development of resistance to LTG. The present study aimed to assess whether LTG-resistant amygdala-kindled rats display subsequent resistance to the VGSC blocker carbamazepine (CBZ) and the broad-spectrum antiepileptic drug (AED) sodium valproate (VPA). Two groups of male Sprague Dawley rats received either 0.5% methylcellulose (MC) or LTG (5mg/kg, i.p.) 1h before each amygdala kindling stimulation. Treatments were stopped once both the groups were fully kindled. Two days later, both groups were challenged with a higher dose of LTG (15mg/kg, i.p.) to verify LTG-resistance in the experimental group (i.e., LTG-pretreated rats). The efficacy of CBZ and VPA was then evaluated in both groups. A higher dose of LTG blocked fully kindled seizures in the vehicle-treated rats but not seizures in the LTG-treated group. The mean seizure score, of the control group (1.2±0.3) was significantly lower (Pkindling acquisition) (28.5% vs. 62%, respectively). Interestingly, CBZ (10, 20, and 40mg/kg) displayed a dose-dependent anticonvulsant effect in the vehicle-kindled group, but was less effective in LTG-treated animals. In contrast, VPA (300mg/kg) effectively blocked the behavioral seizure and decreased the afterdischarge duration (ADD) in both vehicle and LTG groups. These findings suggest that the LTG-resistant, amygdala-kindled rat may represent a novel model of pharmacoresistant epilepsy.

  18. Adsorption characteristics of selected pharmaceuticals and an endocrine disrupting compound-Naproxen, carbamazepine and nonylphenol-on activated carbon.

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    Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

    2008-06-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) (naproxen and carbamazepine) and one endocrine disrupting compound (nonylphenol) were evaluated on two types of activated carbon. When determining their isotherms at environmentally relevant concentration levels, it was found that at this low concentration range (10-800 ng/L), removals of the target compounds were contrary to expectations based on their hydrophobicity. Nonylphenol (log K(ow) 5.8) was most poorly adsorbed, whereas carbamazepine (log K(ow) 2.45) was most adsorbable. Nonylphenol Freundlich isotherms at this very low concentration range had a much higher 1/n compared to isotherms at much higher concentrations. This indicates that extrapolation from an isotherm obtained at a high concentration range to predict the adsorption of nonylphenol at a concentration well below the range of the original isotherm, leads to a substantial overestimation of its removals. Comparison of isotherms for the target compounds to those for other conventional micropollutants suggested that naproxen and carbamazepine could be effectively removed by applying the same dosage utilized to remove odorous compounds (geosmin and MIB) at very low concentrations. The impact of competitive adsorption by background natural organic matter (NOM) on the adsorption of the target compounds was quantified by using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach. The fulfilment of the requirements for applying the simplified IAST-EBC model, which leads to the conclusion that the percentage removal of the target compounds at a given carbon dosage is independent of the initial contaminant concentration, was confirmed for the situation examined in the paper. On this basis it is suggested that the estimated minimum carbon usage rates (CURs) to achieve 90% removal of these emerging contaminants would be valid at concentrations of less than 500 ng/L in

  19. Formulation development and evaluation of novel oral jellies of carbamazepine using pectin, guar gum, and gellan gum

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    Katakam Prakash

    2014-01-01

    Full Text Available Medicated jelly formulations are more suitable for pediatric, geriatric and dysphagic patients, which offer rapid dissolution and absorption of drugs thereby early onset of action. The aim was to develop and evaluate oral jelly formulations of carbamazepine (CBZ. Carbamazepine oral jellies were prepared to employ pectin, guar gum and gellan gum alone and pectin-guar gum combination. Preformulation studies, organoleptic, physical characteristics, drug content, pH, spreadability, rheological properties, syneresis, taste masking, in vitro dissolution testing, drug release kinetics and stability studies were conducted. The Fourier transform infrared and differential scanning calorimeter studies showed that there was no interaction between drug and excipients. The pH of all the formulations was found between pH 6.37 ± 0.03 and 6.83 ± 0.04. The concentration of gelling agents influenced the spreadability. Syneresis was observed in jellies made from guar gum alone, whereas those made from pectin and guar gum it was absent. The optimized formulations (F3, F11 and F15 masked the bitter taste of CBZ and demonstrated acceptable flavor and mouth feel. All formulations showed more than 50% drug release in 15 min except those made of gellan gum alone. The formulations F3, F11 and F15, were found stable for 90 days as per International Conference on Harmonization stability protocol. Carbamazepine jellies made from pectin (F3, 1.2%, gellan gum (F11, 1.5% and pectin-guar gum (F15, 1:0.4% were found more successful and could be employed to improve the palatability and acceptability by pediatric, geriatric and dysphagic patients. The jellies could be useful to overcome the problems of poorly soluble CBZ.

  20. An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine.

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    Plósz, Benedek Gy; Langford, Katherine H; Thomas, Kevin V

    2012-11-01

    Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM-X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full-scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re-transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between

  1. Solubility and dissolution enhancement of HPMC - based solid dispersions of carbamazepine by hot-melt extrusion technique

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    Sharadchandra Dagadu Javeer

    2014-01-01

    Full Text Available The objective of this study was to investigate solid dispersions (SDs of poorly water soluble drug carbamazepine (CBZ, prepared using low viscosity grade hydroxypropyl methyl cellulose (HPMC (Methocel® E3 LV and Methocel® E5 LV by hot-melt extrusion (HME technology. Saturation solubility and dissolution profile of CBZ was studied. Characterization of hot-melt extruded samples was done by Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetry (DSC, and X-ray diffraction studies (XRD. The result of the study showed the conversion of crystalline form of drug into amorphous form indicating increase in saturation solubility and dissolution rate of CBZ.

  2. Erratum to: Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial

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    Hooshang Gerami

    2015-10-01

    Full Text Available Erratum:Affiliation of authors of the article "Effects of oxcarbazepine versus carbamazepine on tinnitus: A randomized double-blind placebo-controlled clinical trial. Ir J neurol 2012; 11(3: 106-110' was changed as:Hooshang Gerami 1, Alia Saberi2, Shadman Nemati1, Ehsan Kazemnejad1, Mohammad Aghajanpour1.1.Department of Otolaryngology , Nose and Sinus Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.2. Department of Neurology, Guilan University of Medical Sciences, Rasht, Iran

  3. Reproductive performance and embriotoxicity of rats exposed to carbamazepine Performance reprodutiva e embriotoxicidade de ratos expostos à carbamazepina

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    Marli Gerenutti

    2008-09-01

    Full Text Available To study the possible effects of carbamazepine in rats during pregnancy and fetuses' physical development, carbamazepine solubilized in propilenglycol was orally administered (20 and 40 mg/kg to the female rats from the 2nd to the 19th days of pregnancy. Propilenglycol was administered to the control group. The animals were sacrificed on the 20th day, when 50% of the offspring were fixed in Bouin's solution and the remaining 50% were submitted to diaphanization. The carbamazepine administration caused reduction on weight gain of pregnant rats and did not damage the females' reproductive performance. In the fetuses' physical development, it was observed a flattening on the skull soft tissues and bones; delay in the skull bone development; cartilage calcification increase between hip and femur and reduction in the number of the sternum ossifications. Although carbamazepine has not caused general changes over female rats' reproductive performance, it produced significant alterations in the development of the fetuses' skeletal parameters.Este trabalho teve como objetivo estudar os possíveis efeitos da administração da carbamazepina na gestação de ratas. A solução glicólica de carbamazepina foi administrada por via oral (20 mg/kg e 40 mg/kg, às ratas do 2º ao 19º dia de gestação. O grupo controle recebeu solução de propilenoglicol. Após a realização da cesária, no 20º dia, 50% dos filhotes foram fixados em Bouin e os outros 50% passaram por processo de diafanização. Estes estudos mostraram que embora a administração de carbamazepina tenha promovido redução do ganho de peso de ratas prenhes, não prejudicou a performance reprodutiva de fêmeas. Nos fetos, observou-se achatamento de tecidos moles e ossos do crânio, retardo no desenvolvimento ósseo do crânio, aumento da calcificação da cartilagem entre o quadril e o fêmur e redução no número de ossificações do esterno. Estes dados, tomados em conjunto, indicam que a

  4. COMPARISON OF COMBINED LITHIUM WITH CARBAMAZEPINE, BENZODIAZEPINES AND NEUROLEPTICS IN TREATMENT OF ACUTE MANIA IN AN INPATIENT STUDY

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    Ahmadi Abhari

    1996-06-01

    Full Text Available The effect of neuroloptics. Carbamacepine and hensmliacepines in treatment of 8.3 patients with acute mania was studied. According to drug types. Patients were divided into 5 groups:"n1 lithium combined with ilubupridol. "n2 Lithium combined with one plxenoshiacine "n3 Lithium combined with two phenothiazines. "n4 Lithium combined with cubumazepine and "n5 Lithium combined with benzxliazepines "nNo singnificunt differences in duration of treatment among the groups were found. According to increased risk of extrapyramidol symptoms in treatment with neuroloptics, carbamazepine or benzxliazepines are preferred in treatment of acute mania as safer comedicutions.  

  5. Neuropsychological effects of antiepileptic drugs (carbamazepine versus valproate in adult males with epilepsy

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    Ghaydaa A Shehata

    2009-10-01

    Full Text Available Ghaydaa A Shehata,1 Abd El-aziz M Bateh,2 Sherifa A Hamed,1 Tarek A Rageh,1 Yaser B Elsorogy11Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Egypt; 2Department of Psychology, Faculty of Arts, Banha University, EgyptPurpose: To evaluate the effect of antiepileptic drugs (AEDs on cognition and behavior in adult epileptic males controlled on treatment with conventional antiepileptic medications. Methods: Cognitive, mood, behavior and personality traits were assessed in 45 epileptic patients treated with carbamazepine and/or valproate and free of seizures for ≥1 year. Thirty-four newly diagnosed or untreated patients with epilepsy and 58 matched healthy subjects were also included for comparison. A battery of psychometric tests was utilized including Stanford-Binet (4th edition, Beck Inventory for Depression, Aggressive Scale and Eysenck Personality Questionnaire.Results: Compared to matched control subjects, treated and untreated epileptic patients had poor performance in different cognitive and behavioral functions testing. Treated patients had worse scores in memory for digits forward and backward, total short-term memory, extroversion and psychosis. The duration of AEDs intake was correlated with memory of objects (r = -0.323; P = 0.030, bead memory (r = -0.314; P = 0.036 and total nonverbal short-term memory (r = -0.346; P = 0.020. Treated and untreated epileptic patients had poor performance of similar extent in behavioral functions testing (depression, aggression and neurosis. The dose of AEDs was correlated with testing scores for neurosis (r = 0.307; P = 0.040, verbal aggression (r = 0.483; P = 0.001 and nonverbal aggression (r = 0.526; P = 0.000, and duration of drug intake was correlated with scores for depression (r = 0.384; P = 0.009, psychosis (r = 0.586; P = 0.0001 and nonverbal aggression (r = 0.300; P = 0.045.Conclusions: This study provides support for the notion that AEDs can impair performance

  6. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

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    Michael R Due

    Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

  7. Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes

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    Chen Chia-Hui

    2012-05-01

    Full Text Available Abstract Background Carbamazepine (CBZ has been used in the treatment of bipolar disorder, both in acute mania and maintenance therapy, since the early 1970s. Here, we report a follow-up study of CBZ-treated bipolar patients in the Taipei City Psychiatric Centre. Methods Bipolar patients diagnosed according to the DSM-IV system and treated with CBZ at the Taipei City Psychiatric Centre had their charts reviewed to evaluate the efficacy and side effects of this medication during an average follow-up period of 10 years. Results A total of 129 bipolar patients (45 males, mean age: 45.7 ± 10.9 year were included in the analysis of CBZ efficacy used alone (n = 63 or as an add-on after lithium (n = 50 or valproic acid (n = 11, or the both of them (n = 5. The mean age of disease onset was 24.6 ± 9.5 years. The mean duration of CBZ use was 10.4 ± 5.2 year. The mean dose used was 571.3 ± 212.6 mg/day with a mean plasma level of 7.8 ± 5.9 μg/mL. Mean body weight increased from 62.0 ± 13.4 kg to 66.7 ± 13.1 kg during treatment. The frequencies of admission per year before and after CBZ treatment were 0.33 ± 0.46 and 0.14 ± 0.30, respectively. The most common side effects targeted the central nervous system (24%, including dizziness, ataxia and cognitive impairment. Other common side effects were gastrointestinal disturbances (3.6%, tremor (3.6%, skin rash (2.9%, and blurred vision (2.9%. Eighty-eight patients (68.2% were taking antipsychotics concomitantly. Ninety-six patients (74.4% needed to use benzodiazepines concomitantly. Sixty-three (48.8% patients had zero episodes in a 10-year follow-up period, compared to all patients having episodes prior to treatment. Using variable analysis, we found better response to CBZ in males than in females. Conclusions CBZ is efficacious in the maintenance treatment of bipolar disorder in naturalistic clinical practice, either as monotherapy

  8. Influence of activated charcoal on the pharmacokinetics and the clinical features of carbamazepine poisoning.

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    Brahmi, Nozha; Kouraichi, Nadia; Thabet, Hafedh; Amamou, Mouldi

    2006-07-01

    Carbamazepine (CBZ) poisoning has been associated with cases of severe toxicity and death. Multiple-dose activated charcoal was proposed to enhance the clearance of CBZ elimination, but there are no prospective controlled studies that demonstrated a change in clinical outcome after the use of multiple-dose activated charcoal. The aim of this study was to determine the CBZ elimination kinetics and the evolution of clinical features according to the dose of activated charcoal in acute poisoning patients. It is a prospective study for 6 months, from January to June 2004, including all pure acute CBZ-poisoned patients. Twelve patients were randomized to receive a multiple-dose activated charcoal (G1) or a simple dose of 1 g/kg (G2). Their mean age was 27.6+/-12.2 years; the Simplified Acute Physiology Score (SAPS II), 16.37+/-8.46; and the Acute Physiology and Chronic Health Evaluation (APACHE II), 8+/-3.96. They were 8 men and 4 women. The mean concentration of blood CBZ at hospital admission was of 29.42+/-6.68 mg/L. Each group includes 6 patients. The peak value of blood CBZ was comparable in the 2 groups: 33+/-3.46 mg/L (G1) vs 32.6+/-5.63 (G2) (P=.5); the requirement of mechanical ventilation was similar also (3 in each group). The duration of both coma and mechanical ventilation was significantly decreased in the first group compared with the second: 20.33+/-3.05 vs 29.33+/-4.11 hours for coma (P=.02) and 24.1+/-4.2 vs 36.4+/-3.6 hours for mechanical ventilation (P=.001). The length of stay was also significantly decreased in the first group: 30.3+/-3.4 vs 39.7+/-7.3 hours in the second group (P=.000006). Concurrently, we have noted a significant constant reduction of the half-life of CBZ from serum in the first group: 12.56+/-3.5 hours after multiple dose vs 27.88+/-7.36 hours after a simple dose (P=.0004). This decrease was correlated to the dose of charcoal. In summary, we can conclude that multiple-dose activated charcoal is more efficient than simple

  9. Carbamazepine degradation using a N-doped TiO2 coated photocatalytic membrane reactor: Influence of physical parameters.

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    Horovitz, Inna; Avisar, Dror; Baker, Mark A; Grilli, Rossana; Lozzi, Luca; Di Camillo, Daniela; Mamane, Hadas

    2016-06-05

    Commercial α-Al2O3 photocatalytic membranes with a pore size of 200 and 800-nm were coated with N-doped TiO2 photocatalytic film using a sol-gel technique for concurrent bottom-up filtration and photocatalytic oxidation. X-ray diffraction confirmed that the deposited N-doped TiO2 films are in the form of anatase with 78-84% coverage of the membrane surface. The concentration of N found by X-ray photoelectron spectroscopy was in the range of 0.3-0.9 atomic percentage. Membrane permeability after coating decreased by 50% and 12% for the 200- and 800-nm membrane substrates, respectively. The impact of operational parameters on the photocatalytic activity (PCA) of the N-doped TiO2-coated membranes was examined in a laboratory flow cell based on degradation of the model micropollutant carbamazepine, using a solar simulator as the light source. The significant gap in degradation rate between flow through the membrane and flow on the surface of the membrane was attributed both to the hydraulic effect and in-pore PCA. N-doped TiO2-coated membranes showed enhanced activity for UV wavelengths, in addition to activity under visible light. Experiments of PCA under varying flow rates concluded that the process is in the mass-transfer control regime. Carbamazepine removal rate increased with temperature, despite the decrease in dissolved oxygen concentration.

  10. Modelling total suspended solids, E. coli and carbamazepine, a tracer of wastewater contamination from combined sewer overflows

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    Pongmala, Khemngeun; Autixier, Laurène; Madoux-Humery, Anne-Sophie; Fuamba, Musandji; Galarneau, Martine; Sauvé, Sébastien; Prévost, Michèle; Dorner, Sarah

    2015-12-01

    Urban source water protection requires knowledge of sources of fecal contamination upstream of drinking water intakes. Combined and sanitary sewer overflows (CSOs and SSOs) are primary sources of microbiological contamination and wastewater micropollutants (WWMPs) in urban water supplies. To quantify the impact of sewer overflows, predictive simulation models are required and have not been widely applied for microbial contaminants such as fecal indicator bacteria and pathogens in urban drainage networks. The objective of this study was to apply a simulation model to estimate the dynamics of three contaminants in sewer overflows - total suspended solids, Escherichia coli (E. coli) and carbamazepine, a WWMP. A mixed combined and pseudo-sanitary drainage network in Québec, Canada was studied and modelled for a total of 7 events for which water quality data were available. Model results were significantly correlated with field water quality data. The model confirmed that the contributions of E. coli from runoff and sewer deposits were minor and their dominant source was from sewage. In contrast, the main sources of total suspended solids were stormwater runoff and sewer resuspension. Given that it is not present in stormwater, carbamazepine was found to be a useful stable tracer of sewage contributions to total contaminant loads and also provided an indication of the fraction of total suspended solids originating from sewer deposits because of its similar response to increasing flowrates.

  11. Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Majeed Ullah

    2015-01-01

    Full Text Available The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25 in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS. At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

  12. Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica [Erratum

    Directory of Open Access Journals (Sweden)

    Wang Z

    2013-02-01

    Full Text Available Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica Wang Z, Chen B, Quan G, et al. International Journal of Nanomedicine. 2012;7:5807–5818.This paper was published without the Supplementary materials.Read the original article

  13. On-line Sweeping Sample Concentration in Micellar Electrokinetic Chromatography with Enhanced Sensitivity for the Determination of Carbamazepine in Human Serum

    Institute of Scientific and Technical Information of China (English)

    Dan Dan HAN; Chun WANG; Zhi WANG; Qiu Hua WU; Xiao Huan ZANG

    2006-01-01

    A sensitive and simple micellar electrokinetic chromatography (MEKC) method was developed for the determination of antiepileptic drug, carbamazepine (CBZ), using sweeping on-line concentration method with photodiode array detection. Under the optimal conditions, the method has been successfully applied to the analysis of CBZ in human serum.

  14. Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica

    Directory of Open Access Journals (Sweden)

    Li G

    2012-11-01

    Full Text Available Zhouhua Wang,1,2 Bao Chen,1 Guilan Quan,1 Feng Li,1 Qiaoli Wu,1 Linghui Dian,1 Yixuan Dong,1 Ge Li,2 Chuanbin Wu1,21School of Pharmaceutical Sciences, 2Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaBackground and methods: The aim of this study was to develop an immediate-release pellet formulation with improved drug dissolution and adsorption. Carbamazepine, a poorly water-soluble drug, was adsorbed into mesoporous silica (SBA-15-CBZ via a wetness impregnation method and then processed by extrusion/spheronization into pellets. Physicochemical characterization of the preparation was carried out by scanning electron microscopy, transmission electron microscopy, nitrogen adsorption, small-angle and wide-angle x-ray diffraction, and differential scanning calorimetry. Flowability and wettability of the drug-loaded silica powder were evaluated by bulk and tapped density and by the angle of repose and contact angle, respectively. The drug-loaded silica powder was formulated into pellets to improve flowability.Results: With maximum drug loading in SBA-15 matrices determined to be 20% wt, in vitro release studies demonstrated that the carbamazepine dissolution rate was notably improved from both the SBA-15 powder and the corresponding pellets as compared with the bulk drug. Correspondingly, the oral bioavailability of SBA-15-CBZ pellets was increased considerably by 1.57-fold in dogs (P < 0.05 compared with fast-release commercial carbamazepine tablets.Conclusion: Immediate-release carbamazepine pellets prepared from drug-loaded silica provide a feasible approach for development of a rapidly acting oral formulation for this poorly water-soluble drug and with better absorption.Keywords: ordered mesoporous silica, poorly water-soluble drug, carbamazepine, extrusion, spheronization, pellets, bioavailability

  15. Influence of sodium lauryl sulfate and tween 80 on carbamazepine-nicotinamide cocrystal solubility and dissolution behaviour.

    Science.gov (United States)

    Li, Mingzhong; Qiao, Ning; Wang, Ke

    2013-10-11

    The influence of the surfactants of sodium lauryl sulfate (SLS) and Tween 80 on carbamazepine-nicotinamide (CBZ-NIC) cocrystal solubility and dissolution behaviour has been studied in this work. The solubility of the CBZ-NIC cocrystal was determined by measuring the eutectic concentrations of the drug and the coformer. Evolution of the intrinsic dissolution rate (IDR) of the CBZ-NIC cocrystal was monitored by the UV imaging dissolution system during dissolution. Experimental results indicated that SLS and Tween 80 had little influence upon the solubility of the CBZ-NIC cocrystal but they had totally opposite effects on the IDR of the CBZ-NIC cocrystal during dissolution. SLS significantly increased the IDR of the CBZ-NIC cocrystal while Tween 80 decreased its IDR.

  16. The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation

    Institute of Scientific and Technical Information of China (English)

    Jun-jie DING; Yun-jian ZHANG; Zheng JIAO; Yi WANG

    2012-01-01

    Aim:To study the effects of delayed and missed doses (poor compliance) on the pharmacokinetics of carbamazepine (CBZ) and its main active metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese epilepsy patients using Monte Carlo simulation.Methods:CBZ and CBZE time-concentration profiles in various scenarios were generated based on a population pharmacokinetic study in Chinese epilepsy patients using Monte Carlo simulation.The scenarios included patients given multiple doses of CBZ that ranged from 100 to 300 mg three times daily or from 200 to 300 mg every 12 h.The therapeutic range of CBZ and CBZE for each scenario was estimated to assess the effect of delayed or missed doses and to design corresponding rescue regimens.Moreover,the impact of body weight,absorption rate and co-therapy with other antiepileptic drugs (phenytoin,phenobarbital and valproic acid) on the dosage recommendation was investigated in the event of poor compliance.Results:The risk for a sub-therapeutic range of CBZ and CBZE was increased in a dose-dependent manner in both two and three times daily regimens when delayed or missed doses occurred.The effects of poor compliance was less prominent on the lower daily doses compared with those on the higher daily doses.The dose recommendations,in the event of poor compliance,were time related and dose dependent.Patient body weight,absorption rate and co-therapy with phenytoin,phenobarbital and valproic acid had no significant impact on the dose recommendation.Conclusion:Patients with epilepsy should take the delayed doses as soon as they remember,and partial missed doses may need to be taken near or at the next scheduled time.

  17. Second-order advantage with excitation–emission photoinduced fluorimetry for the determination of the antiepileptic carbamazepine in environmental waters

    Energy Technology Data Exchange (ETDEWEB)

    Lozano, Valeria A.; Escandar, Graciela M., E-mail: escandar@iquir-conicet.gov.ar

    2013-06-11

    Graphical abstract: -- Highlights: •A simple and safe method for the emerging contaminant carbamazepine is developed. •MCR-ALS algorithm allows us the quantification in very interfering media. •Determination is accomplished in natural waters using green-chemistry principles. -- Abstract: A photochemically induced fluorescence system combined with second-order chemometric analysis for the determination of the anticonvulsant carbamazepine (CBZ) is presented. CBZ is a widely used drug for the treatment of epilepsy and is included in the group of emerging contaminant present in the aquatic environment. CBZ is not fluorescent in solution but can be converted into a fluorescent compound through a photochemical reaction in a strong acid medium. The determination is carried out by measuring excitation–emission photoinduced fluorescence matrices of the products formed upon ultraviolet light irradiation in a laboratory-constructed reactor constituted by two simple 4 W germicidal tubes. Working conditions related to both the reaction medium and the photoreactor geometry are optimized by an experimental design. The developed approach enabled the determination of CBZ at trace levels without the necessity of applying separation steps, and in the presence of uncalibrated interferences which also display photoinduced fluorescence and may be potentially present in the investigated samples. Different second-order algorithms were tested and successful resolution was achieved using multivariate curve resolution-alternating least-squares (MCR-ALS). The study is employed for the discussion of the scopes and yields of each of the applied second-order chemometric tools. The quality of the proposed method is probed through the determination of the studied emerging pollutant in both environmental and drinking water samples. After a pre-concentration step on a C18 membrane using 50.0 mL of real water samples, a prediction relative error of 2% and limits of detection and

  18. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-11-15

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD{sub 7} m{sup -3}d{sup -1}. Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k{sub biol}) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g{sub SS}{sup −1} d{sup −1}. Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k{sub biol} constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge.

  19. Effects of topiramate and carbamazepine on thyroid hormone level in adults with epilepsy

    Institute of Scientific and Technical Information of China (English)

    Liang Yu; Yulan Huang; Hongbin Sun; Jie Liu; Fei Xu; Xiaoping Wang

    2006-01-01

    BACKGROUND: It has been demonstrated that traditional antiepileptics, such as phenytoin, carbamazepine (CBZ), phenobarbital, etc., can result in the decrease of thyroid hormone of epileptic patients. However, there is still no sufficient evidence for the studies about the effect of new-type antiepileptics, such as topiramate (TPM),on thyroid hormones.OBJECTIVE: To observe the effects of TPM and CBZ on the level of thyroid hormones in serum of adults with epilepsy.DESIGN: A comparative observation.SETTING: Department of Neurology, Sichuan Provincial People's Hospital.PARTICIPANTS: Totally 100 outpatients or inpatients newly diagnosed to have epilepsy were selected from the Department of Neurology, Sichuan Provincial People's Hospital from July 2003 to August 2005, including 60males and 40 females, aged 18-70 years. All the patients were accorded with the standard for the classification of epilepsy set by International League Against Epilepsy (ILAE) in 1981; Had been Informed and agreed with the detection; Had no history of thyroid gland disease; Had not taken any drugs could affect the thyroid function. Meanwhile, 40 adult healthy examinees were selected from our hospital as the control group, including24 males and 16 females, aged 18-65 years.METHODS: ① The 100 epileptic patients were randomly divided into TPM group (n =50) and CBZ group (n =50),and they were treated with TPM (Xian-Janssen Pharmaceutical, Ltd.; Batch number: 03AS032, Norm: 25mg/tablet) and CBZ (Shanghai Sunve Pharmaceutical Co., Ltd.; Batch number: 030201, Norm: 100 mg/tablet)respectively. The initial dosage of TPM was 25 mg per day, increased by 25 mg every week, the objective dosage of 100-200 mg per day was maintained when the symptoms were satisfactorily controlled. The dosage of CBZ was 6-8 mg/kg per day. All the patients were administrated for 1 year. ② The serum levels of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and thyroid

  20. Interactions of levetiracetam with carbamazepine, phenytoin, topiramate and vigabatrin in the mouse 6Hz psychomotor seizure model - a type II isobolographic analysis.

    Science.gov (United States)

    Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Luszczki, Jarogniew J

    2014-01-15

    The aim of the presented study was to characterize the anticonvulsant effects of levetiracetam in combination with various antiepileptic drugs (carbamazepine, phenytoin, topiramate and vigabatrin) in the mouse 6Hz psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32mA, 6Hz, 3s stimulus duration) delivered via ocular electrodes; type II isobolographic analysis was used to characterize the consequent anticonvulsant interactions between the various drug combinations for fixed-ratios of 1:1, 1:2, 1:5 and 1:10. With type II isobolographic analysis, the combinations of levetiracetam with carbamazepine and phenytoin for the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; P<0.01) in terms of seizure suppression, while the combinations for the fixed-ratios of 1:1 and 1:2 were additive. Levetiracetam combined with topiramate and vigabatrin for the fixed-ratio of 1:10 exerted supra-additive interaction (P<0.05), and simultaneously, the two-drug combinations for the fixed-ratios of 1:1, 1:2 and 1:5 produced additive interaction in the mouse 6Hz psychomotor seizure model. The combinations of levetiracetam with carbamazepine and phenytoin for the fixed-ratios of 1:5 and 1:10, as well as the combinations of levetiracetam with topiramate and vigabatrin for the fixed-ratio of 1:10 appear to be particularly favorable combinations exerting supra-additive interaction in the mouse 6Hz psychomotor seizure model. Finally, it may be concluded that because of the synergistic interactions between levetiracetam and carbamazepine, phenytoin, topiramate and vigabatrin, the combinations might be useful in clinical practice.

  1. A novel disposable electrochemical sensor for determination of carbamazepine based on Fe doped SnO{sub 2} nanoparticles modified screen-printed carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Lavanya, N. [Department of Biosensors and Bioelectronics, Alagappa University, Karaikudi 630003, TN (India); Department of Electronic Engineering, Chemistry and Materials Engineering, University of Messina, Messina 98166 (Italy); Sekar, C., E-mail: Sekar2025@gmail.com [Department of Biosensors and Bioelectronics, Alagappa University, Karaikudi 630003, TN (India); Ficarra, S.; Tellone, E. [Department of Chemical Sciences, University of Messina, Messina 98166 (Italy); Bonavita, A.; Leonardi, S.G.; Neri, G. [Department of Electronic Engineering, Chemistry and Materials Engineering, University of Messina, Messina 98166 (Italy)

    2016-05-01

    An effective strategy to fabricate a novel disposable screen printing carbon electrode modified by iron doped tin dioxide nanoparticles for carbamazepine (CBZ) detection has been developed. Fe–SnO{sub 2} (Fe = 0 to 5 wt.%) NPs were synthesized by a simple microwave irradiation method and assessed for their structural and morphological changes due to Fe doping into SnO{sub 2} matrix by X-ray diffraction and scanning and transmission electron microscopy. The electrochemical behaviour of carbamazepine at the Fe–SnO{sub 2} modified screen printed carbon electrode (SPCE) was investigated by cyclic voltammetry and square wave voltammetry. Electron transfer coefficient α (0.63) and electron transfer rate constant k{sub s} (0.69 s{sup −1}) values of the 5 wt.% Fe–SnO{sub 2} modified SPCE indicate that the diffusion controlled process takes place on the electrode surface. The fabricated sensor displayed a good electrooxidation response towards the detection of CBZ at a lower oxidation potential of 0.8 V in phosphate buffer solution at pH 7.0. Under the optimal conditions, the sensor showed fast and sensitive current response to CBZ over a wide linear range of 0.5–100 μM with a low detection limit of 92 nM. Furthermore, the practical application of the modified electrode has been investigated by the determination of CBZ in pharmaceutical products using standard addition method. - Highlights: • A novel mediator-free disposable screen printed carbon electrode has been fabricated based on Fe- SnO{sub 2} nanoparticles for determination of carbamazepine • The Fe-SnO{sub 2}/SPCE showed wide linear range (0.5–100 μM), low detection limit (92 nM), high sensitivity, good stability and reproducibility. • The carbamazepine sensor was successfully applied to the analysis of pharmaceutical products with satisfactory recoveries.

  2. The association between Parkinson's disease and anti-epilepsy drug carbamazepine: a case–control study using the UK General Practice Research Database

    OpenAIRE

    Skow, A.; Douglas, I.; Smeeth, L.

    2013-01-01

    AIM: To investigate whether the use of carbamazepine is associated with reduced risk of Parkinson's disease. METHODS: We conducted a population-based matched case-control study of patients randomly selected from the UK General Research Practice Database (GPRD). We identified 8,549 patients with Parkinson's disease using diagnosis criteria with a positive predictive value of 90%. These patients were compared with 42,160 controls matched for age, sex, and general practice. RESULTS: Overall, 3.0...

  3. Transformation of atenolol, metoprolol, and carbamazepine in soils: The identification, quantification, and stability of the transformation products and further implications for the environment.

    Science.gov (United States)

    Koba, Olga; Golovko, Oksana; Kodešová, Radka; Klement, Aleš; Grabic, Roman

    2016-11-01

    Pharmaceuticals are a large group of substances that have been recognized as environmental contaminants in recent years. Research on the pharmaceutical fate in soils is currently limited or missing. In this study, three pharmaceuticals (atenolol (ATE), carbamazepine (CAR), and metoprolol (MET)) were introduced to soils and exposed for 61 day under aerobic conditions. Thirteen different soils were used in the study to increase the understanding of pharmaceutical behaviour in the soil matrix. Ten metabolites were detected and tentatively identified. Some of them, such as atenolol acid (AAC), carbamazepine 10,11-epoxide (EPC), 10,11-dihydrocarbamazepine (DHC), trans-10,11-Dihydro-10,11-dihydroxy carbamazepine (RTC), and metoprolol acid (MAC), were consequently confirmed using commercial reference standards. It was concluded that the aerobic conditions of the experiment determined the pharmaceutical degradation pathway of studied compounds in the soils. The different amounts/rates and degradation of the transformation products can be attributed to differences in the soil properties. ATE degraded relatively quickly compared with CAR, whereas MET degradation in the soils was unclear. The persistence of CAR and its metabolites, in combination with low CAR sorption, enable the transportation of CAR and its metabolites within soils and into the ground water. Thus, CAR may cause adverse effects on the environment and humans.

  4. Molecularly imprinted polymer on a SiO2 -coated graphene oxide surface for the fast and selective dispersive solid-phase extraction of Carbamazepine from biological samples.

    Science.gov (United States)

    Khalilian, Faezeh; Ahmadian, Setareh

    2016-04-01

    A surface carbamazepine-imprinted polymer was grafted and synthesized on the SiO2 /graphene oxide surface. Firstly SiO2 was coated on synthesized graphene oxide sheet using the sol-gel technique. Prior to polymerization, the vinyl group was incorporated on to the surface of SiO2 /graphene oxide to direct selective polymerization on the surface. Methacrylic acid, ethylene glycol dimethacrylate and ethanol were used as monomer, cross-linker and porogen, respectively. Nonimprinted polymer was also prepared for comparison. The properties of the molecularly imprinted polymer were characterized using field-emission scanning electron microscopy and Fourier-transform infrared spectroscopy. The surface molecularly imprinted polymer was utilized as an adsorbent of dispersive solid-phase extraction for separation and preconcentration of carbamazepine. The effects of the different parameters influencing the extraction efficiency, such as sample pH were investigated and optimized. The specificity of the molecular imprinted polymer over the nonimprinted polymer was examined in absence and presence of competitive drugs. The carbamazepine calibration curve showed linearity in the ranges 0.5-500 μg/L. The limits of detection and quantification under the optimized conditions were 0.1 and 0.3 μg/L, respectively. The within-day and between-day relative standard deviations (n = 3) were 3.6 and 4.3%, respectively. Furthermore, the relative recoveries for spiked biological samples were above 85%.

  5. Kinetic changes and modulation by carbamazepine on voltage-gated sodium channels in rat CA1 neurons after epilepsy

    Institute of Scientific and Technical Information of China (English)

    Guang-chun SUN; Taco WERKMAN; Wytse J WADMAN

    2006-01-01

    Aim: To study whether the functional properties of sodium channels, and subsequently the channel modulation by carbamazepine (CBZ) in hippocampal CA1 neurons can be changed after epileptic seizures. Methods: We used the acutely dissociated hippocampal CA1 pyramidal cells from epilepsy model rats 3 weeks and 3 months respectively after kainate injection, and whole-cell voltage-clamp techniques. Results: After long-term epileptic seizures, both sodium channel voltage-dependence of activation and steady-state inactivation shifted to more hyperpolarizing potentials, which resulted in the enlarged window current; the membrane density of sodium current decreased and the time constant of recovery from inactivation increased. CBZ displayed unchanged efficacy on sodium channels, with a similar binding rate to them, except that at higher concentrations, the voltage shift of inactivation was reduced. For the short-term kainate model rats, no differences were detected between the control and epilepsy groups. Conclusion: These results indicate that the properties of sodium channels in acutely dissociated hippocampal neurons could be changed following long-term epilepsy, but the alternation might not be enough to induce the channel resistance to CBZ.

  6. Degradation of carbamazepine by UV/chlorine advanced oxidation process and formation of disinfection by-products.

    Science.gov (United States)

    Zhou, Shiqing; Xia, Ying; Li, Ting; Yao, Tian; Shi, Zhou; Zhu, Shumin; Gao, Naiyun

    2016-08-01

    Pharmaceuticals in water are commonly found and are not efficiently removed by current treatment processes. Degradation of antiepileptic drug carbamazepine (CBZ) by UV/chlorine advanced oxidation process was systematically investigated in this study. The results showed that the UV/chlorine process was more effective at degrading CBZ than either UV or chlorination alone. The CBZ degradation followed pseudo-first order reaction kinetics, and the degradation rate constants (kobs) were affected by the chlorine dose, solution pH, and natural organic matter concentration to different degrees. Degradation of CBZ greatly increased with increasing chlorine dose and decreasing solution pH during the UV/chlorine process. Additionally, the presence of natural organic matter in the solution inhibited the degradation of CBZ. UV photolysis, chlorination, and reactive species (hydroxyl radical •OH and chlorine atoms •Cl) were identified as responsible for CBZ degradation in the UV/chlorine process. Finally, a degradation pathway for CBZ in the UV/chlorine process was proposed and the formation potentials of carbonaceous and nitrogenous disinfection by-products were evaluated. Enhanced formation of trichloroacetic acid, dichloroacetonitrile, and trichloronitromethane precursors should be considered when applying UV/chlorine advanced oxidation process to drinking water.

  7. Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets.

    Science.gov (United States)

    Qiu, Shi; Li, Mingzhong

    2015-02-01

    The aim of this study was to investigate the effects of coformers on phase transformation and release profiles of carbamazepine (CBZ) cocrystals in hydroxypropyl methylcellulose (HPMC) based matrix tablets. It has been found that selection of different coformers of saccharin (SAC) and cinnamic acid (CIN) can affect the stability of CBZ cocrystals in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of CBZ-SAC cocrystals can only be shown for a short period during dissolution because of the fast conversion to its dihydrate form (DH). HPMC can partially inhibit the crystallisation of CBZ DH during dissolution of CBZ-SAC cocrystal. However, the increased viscosity of HPMC dissolution medium reduced the dissolution rate of CBZ-SAC cocrystals. Therefore the CBZ-SAC cocrystal formulation did not show any significant advantage in CBZ release rate. In contrast the improved CBZ dissolution rate of CBZ-CIN cocrystal can be realised in both solution and formulation due to its high stability. In conclusion, exploring and understanding the mechanisms of the phase transformation of pharmaceutical cocrystals in aqueous medium for selection of lead cocrystals is the key for success of product development.

  8. Effect of carbamazepine or phenytoin therapy on blood level of intravenously administered midazolam: a prospective cohort study.

    Science.gov (United States)

    Hayashi, Tomoko; Higuchi, Hitoshi; Tomoyasu, Yumiko; Ishii-Maruhama, Minako; Maeda, Shigeru; Miyawaki, Takuya

    2016-02-01

    Dental treatment of intellectually disabled patients is frequently performed under general anesthesia or sedation. Many of these patients have epilepsy and are medicated with antiepileptic drugs (AEDs). Carbamazepine (CBZ) and phenytoin (PHT) are known to promote the metabolism of midazolam, and the blood levels of midazolam in patients medicated with CBZ or PHT may be different from those in healthy individuals. In this study, we clarified the influences of CBZ and PHT on the blood level of intravenously administered midazolam in patients medicated with CBZ or PHT. The subjects were divided into the following groups: not medicated with AEDs (control group), medicated with only CBZ or PHT (mono CBZ/PHT group), and medicated with CBZ or PHT or both and other AEDs (poly CBZ/PHT group). General anesthesia was achieved using midazolam, propofol, and remifentanil, and then the blood midazolam level was measured at 10, 30, and 60 min after intravenous midazolam administration. According to the results, the blood midazolam level was significantly lower in the mono and poly CBZ/PHT groups than in the control group. This finding suggests that intravenously administered midazolam may have a weaker effect in patients medicated with CBZ or PHT.

  9. Transformation of the recalcitrant pharmaceutical compound carbamazepine by Pleurotus ostreatus: role of cytochrome P450 monooxygenase and manganese peroxidase.

    Science.gov (United States)

    Golan-Rozen, Naama; Chefetz, Benny; Ben-Ari, Julius; Geva, Joseph; Hadar, Yitzhak

    2011-08-15

    Carbamazepine (CBZ) is an environmentally recalcitrant compound highly stable in soil and during wastewater treatment. In this study, we examined the mechanisms by which the white-rot fungus Pleurotus ostreatus metabolizes CBZ in liquid culture using a physiological approach. P. ostreatus PC9 was grown in media known to support different levels of a multiplicity of enzyme systems such as cytochrome P450 (CYP450) and manganese peroxidase (MnP). When both CYP450 and MnP systems were active, 99% of the added CBZ was eliminated from the solution and transformed to 10,11-epoxycarbamazepine. High removal of CBZ was also obtained when either MnP or CYP450 was active. When both CYP450 and MnP were inactivated, only 10 to 30% of the added CBZ was removed. In this latter system, removal of CBZ might be partially attributed to the activity of versatile peroxidase. P. ostreatus was able to eliminate CBZ in liquid culture even when CBZ was added at an environmentally relevant concentration (1 μg L(-1)). On the basis of our study, we suggest that two families of enzymes are involved in the oxidation of CBZ in liquid culture: MnP in a Mn(2+)-dependent or independent manner and CYP450. Our study also highlights the potential of using P. ostreatus for bioremediation systems.

  10. Multiple organ system damage caused by carbamazepine%卡马西平致多系统损害

    Institute of Scientific and Technical Information of China (English)

    唐小飞; 谭兵; 张艳; 刘洪军; 杨猛; 陈丽娟; 杨志祥

    2016-01-01

    A 79-years-old male patient took carbamazepine 100 mg thrice daily for the trigeminal neuralgia and added the dose of carbamazepine to 200 mg thrice daily by himself because the pain could not be controlled.One month later,the patient developed shortness of breath,heart palpitations,dizziness,and limbs numbness.Laboratory tests showed the following results:white blood cell (WBC) 3.0 × 109/L,red blood cell (RBC) 3.1 × 1012/L,hemoglobin (Hb) 100 g/L,serum sodium 127 mmol/L,chloride 95 mmol/L,total thyroxine 58 nmol/L,free thyroxine 10.6 pmol/L,thyroid-stimulating hormone (TSH) 4.5 mU/L.Dynamic electrocardiogram showed average heart rate 59 beats/min and 326 times of cardiac arrest exceeding 2.0 s.He was diagnosed with sick sinus syndrome and hypothyroidism.The patient was discharged after symptomatic treatments.About 3 months later,shortness of breath,dizziness and heart palpitations appeared again,accompanied by syncope 2 times (about 1 minute each time and relieved spontaneously).Laboratory tests showed the following results:WBC 3.1 × 109/L,RBC 3.0 × 1012/L,Hb 99 g/L,serum sodium 127 mmol/L,chloride 95 mmol/L,total thyroxine 63 nmol/L,free thyroxine 11.8 pmol/L,TSH 7.9 mU/L.Dynamic electrocardiogram showed arrhythmia,atrioventricular block,and R-R interval prolongation.Carbamazepine was stopped.Ten days later,dizziness,heart palpitations,and syncope disappeared.The laboratory revealed the following results:WBC 5.6 × 109/L,RBC 4.4 × 1012/L,Hb 120 g/L,serum sodium 139 mmol/L,chloride 102 mmol/L,total thyroxine 67 nmol/L,free thyroxine 15.0 pmol/L,TSH 3.8 mU/L.Dynamic electrocardiogram showed sinus heart rate and heart rate 75 beats/ min.Carbamazepine 100 mg thrice daily was administered again for trigeminal neuralgia.The above mentioned symptoms did not recur during a half year of follow-up.%1例79岁男性三叉神经痛患者长期服用卡马西平(100 mg,3次/d),因疼痛控制不佳自行增加剂量(200 mg,3次/d).1个月后,患者出现气促、心悸

  11. Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model

    Directory of Open Access Journals (Sweden)

    Homšek Irena

    2011-01-01

    Full Text Available Controlled-release (CR pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

  12. Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats

    Institute of Scientific and Technical Information of China (English)

    Qing LI; Chun-lei JIN; Li-sha XU; Zheng-bin ZHU-GE; Li-xia YANG; Lu-ying LIU; Zhong CHEN

    2005-01-01

    Aim: To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. Methods:Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and γ-aminobutyric acid levels were measured by high performance liquid chromatography (HPLC). Results: Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no meliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. Conclusion: Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.

  13. Mechanistic differences in permeation behavior of supersaturated and solubilized solutions of carbamazepine revealed by nuclear magnetic resonance measurements.

    Science.gov (United States)

    Ueda, Keisuke; Higashi, Kenjirou; Limwikrant, Waree; Sekine, Shuichi; Horie, Toshiharu; Yamamoto, Keiji; Moribe, Kunikazu

    2012-11-05

    A solid dispersion (SPD) of carbamazepine (CBZ) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was prepared by the spray drying method. The apparent solubility (37 °C, pH 7.4) of CBZ observed with the SPD was over 3 times higher than the solubility of unprocessed CBZ. The supersaturated solution was stable for 7 days. A higher concentration of CBZ in aqueous medium was also achieved by mixing with Poloxamer 407 (P407), a solubilizing agent. From permeation studies of CBZ using Caco-2 monolayers and dialysis membranes, we observed improved CBZ permeation across the membrane in the supersaturated solution of CBZ/HPMC-AS SPD. On the contrary, the CBZ-solubilized P407 solution exhibited poor permeation by CBZ. The chemical shifts of CBZ on the (1)H NMR spectrum from CBZ/HPMC-AS SPD solution were not altered significantly by coexistence with HPMC-AS. In contrast, an upfield shift of CBZ was observed in the CBZ/P407 solution. The spin-lattice relaxation time (T(1)) over spin-spin relaxation time (T(2)) indicated that the mobility of CBZ in the HPMC-AS solution was much lower than that in water. Meanwhile, the mobility of CBZ in P407 solution was significantly higher than that in water. NMR data indicate that CBZ does not strongly interact with HPMC-AS. CBZ mobility was suppressed due to self-association and microviscosity around CBZ, which do not affect permeation behavior. Most of the CBZ molecules in the CBZ/P407 solution were solubilized in the hydrophobic core of P407, and a few were free to permeate the membrane. The molecular state of CBZ, as evaluated by NMR measurements, directly correlated with permeation behavior.

  14. Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid.

    Science.gov (United States)

    Levy, R H; Rettenmeier, A W; Anderson, G D; Wilensky, A J; Friel, P N; Baillie, T A; Acheampong, A; Tor, J; Guyot, M; Loiseau, P

    1990-09-01

    The incidence of valproic acid hepatotoxicity has been reported to increase in patients who are receiving polytherapy. A minor valproic acid metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA), formed by a cytochrome P450-mediated reaction, has been shown to be a potent inducer of microvesicular steatosis in rats. This study tested the hypothesis that formation of 4-ene-VPA would be increased in patients taking valproic acid with carbamazepine or with phenytoin but decreased with coadministration of an inhibitor of cytochrome P450 (the antiepileptic drug stiripentol in 300 to 1200 mg daily doses) in healthy subjects. Blood and urine samples in the studies were collected during a dosing interval at steady state. Valproic acid was assayed in plasma by capillary gas chromatography; valproic acid and 15 metabolites were measured in urine by gas chromatography/mass spectrometry. The formation clearance (CLf) of 4-ene-VPA was increased twofold in the valproic acid-carbamazepine and valproic acid-phenytoin groups. In the valproic acid/stiripentol studies, the CLf of 4-ene-VPA decreased by 32% in the 1200 mg/day stiripentol study. Similar findings were obtained at 600 and 300 mg/day stiripentol. These findings provide evidence supporting a role for cytochrome P450 in the formation of the hepatotoxic metabolite, 4-ene-VPA, in humans. The increased formation of 4-ene-VPA associated with carbamazepine and phenytoin is striking in relation to the epidemiologic finding of increased incidence of valproic acid-related hepatotoxicity during polytherapy with P450 inducers.

  15. Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting.

    Science.gov (United States)

    Djuris, Jelena; Nikolakakis, Ioannis; Ibric, Svetlana; Djuric, Zorica; Kachrimanis, Kyriakos

    2013-05-01

    Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed ∼5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.

  16. Synergistic effect between UV and chlorine (UV/chlorine) on the degradation of carbamazepine: Influence factors and radical species.

    Science.gov (United States)

    Wang, Wen-Long; Wu, Qian-Yuan; Huang, Nan; Wang, Ting; Hu, Hong-Ying

    2016-07-01

    For successful wastewater reclamation, advanced oxidation processes have attracted attention for elimination of emerging contaminants. In this study, the synergistic treatment with UV irradiation and chlorine (UV/chlorine) was used to degrade carbamazepine (CBZ). Neither UV irradiation alone nor chlorination alone could efficiently degraded CBZ. UV/chlorine oxidation showed a significant synergistic effect on CBZ degradation through generation of radical species (OH and Cl), and this process could be well depicted by pseudo first order kinetic. The degradation rate constants (kobs,CBZ) of CBZ increased linearly with increasing UV irradiance and chlorine dosage. The degradation of CBZ by UV/chlorine in acidic solutions was more efficient than that in basic solutions mainly due to the effect of pH on the dissociation of HOCl and OCl(-) and then on the quantum yields and radical species quenching of UV/chlorine. When pH was increased from 5.5 to 9.5, the rate constants of degradation of CBZ by OH decreased from 0.65 to 0.14 min(-1) and that by Cl decreased from 0.40 to 0.11 min(-1). The rate constant for the reaction between Cl and CBZ was 5.6 ± 1.6 × 10(10) M(-1) s(-1). Anions of HCO3(-) (1-50 mM) showed moderate inhibition of CBZ degradation by UV/chlorine, while Cl(-) did not. UV/chlorine could efficiently degrade CBZ in wastewater treatment plant effluent, although the degradation was inhibited by about 30% compared with that in ultrapure water with chlorine dosage of 0.14-0.56 mM. Nine main oxidation products of the CBZ degradation by UV/chlorine were identified using the HPLC-QToF MS/MS. Initial oxidation products arose from hydroxylation, carboxylation and hydrogen atom abstraction of CBZ by OH and Cl, and were then further oxidized to generate acylamino cleavage and decarboxylation products of acridine and acridione.

  17. Amitriptyline and carbamazepine utilize voltage-gated ion channel suppression to impair excitability of sensory dorsal horn neurons in thin tissue slice: An in vitro study.

    Science.gov (United States)

    Wolff, Matthias; Czorlich, Patrick; Nagaraj, Chandran; Schnöbel-Ehehalt, Rose; Li, Yingji; Kwapiszewska, Grazyna; Olschewski, Horst; Heschl, Stefan; Olschewski, Andrea

    2016-08-01

    Amitriptyline, carbamazepine and gabapentin are often used for the treatment of neuropathic pain. However, their analgesic action on central sensory neurons is still not fully understood. Moreover, the expression pattern of their target ion channels is poorly elucidated in the dorsal horn of the spinal cord. Thus, we performed patch-clamp investigations in visualized neurons of lamina I-III of the spinal cord. The expression of the different voltage-gated ion channels, as the targets of these drugs, was detected by RT-PCR and immunohistochemistry. Neurons of the lamina I-III express the TTX-sensitive voltage-gated Na(+) as well as voltage-gated K(+) subunits assembling the fast inactivating (A-type) currents and the delayed rectifier K(+) currents. Our pharmacological studies show that tonically-firing, adapting-firing and single spike neurons responded dose-dependently to amitriptyline and carbamazepine. The ion channel inhibition consecutively reduced the firing rate of tonically-firing and adapting-firing neurons. This study provides evidence for the distribution of voltage-gated Na(+) and K(+) subunits in lamina I-III of the spinal cord and for the action of drugs used for the treatment of neuropathic pain. Our work confirms that modulation of voltage-gated ion channels in the central nervous system contributes to the antinociceptive effects of these drugs.

  18. A novel disposable electrochemical sensor for determination of carbamazepine based on Fe doped SnO2 nanoparticles modified screen-printed carbon electrode.

    Science.gov (United States)

    Lavanya, N; Sekar, C; Ficarra, S; Tellone, E; Bonavita, A; Leonardi, S G; Neri, G

    2016-05-01

    An effective strategy to fabricate a novel disposable screen printing carbon electrode modified by iron doped tin dioxide nanoparticles for carbamazepine (CBZ) detection has been developed. Fe-SnO2 (Fe=0 to 5 wt.%) NPs were synthesized by a simple microwave irradiation method and assessed for their structural and morphological changes due to Fe doping into SnO2 matrix by X-ray diffraction and scanning and transmission electron microscopy. The electrochemical behaviour of carbamazepine at the Fe-SnO2 modified screen printed carbon electrode (SPCE) was investigated by cyclic voltammetry and square wave voltammetry. Electron transfer coefficient α (0.63) and electron transfer rate constant ks (0.69 s(-1)) values of the 5 wt.% Fe-SnO2 modified SPCE indicate that the diffusion controlled process takes place on the electrode surface. The fabricated sensor displayed a good electrooxidation response towards the detection of CBZ at a lower oxidation potential of 0.8 V in phosphate buffer solution at pH7.0. Under the optimal conditions, the sensor showed fast and sensitive current response to CBZ over a wide linear range of 0.5-100 μM with a low detection limit of 92 nM. Furthermore, the practical application of the modified electrode has been investigated by the determination of CBZ in pharmaceutical products using standard addition method.

  19. Solidified floating organic drop microextraction combined with high performance liquid chromatography for the determination of carbamazepine in human plasma and urine samples

    Institute of Scientific and Technical Information of China (English)

    Mohammad ASADI; Ali Mohammad HAJI SHABANI; Shayessteh DADFARNIA; Bijan ABBASI

    2015-01-01

    Solidified floating organic drop microextraction( SFODME)in combination with high performance liquid chromatography was used for separation/preconcentration and determination of carbamazepine( CBZ)in human plasma and urine samples. Parameters that affect the extraction efficiency such as the type and volume of extraction solvent,ionic strength,sodium hydroxide concentration,stirring rate,sample volume and extrac-tion time,were investigated and optimized. Under the optimum conditions( extraction solvent,40 μL of 1-un-decanol;sodium hydroxide concentration,1 mol/L;temperature,50 ℃;stirring speed,400 r/min;sample vol-ume,8 mL;sodium chloride concentration,3%( w/v)and extraction time,60 min)the calibration curve was found to be linear in the mass concentration range of 0. 4-700. 0 μg/L. The limit of detection( LOD)was 0. 1μg/L and the relative standard deviation( RSD)for six replicate extraction and determination of carbamazepine at 100 μg/L level was found to be 4. 1%. The method was successfully applied to the determination of CBZ in human plasma and urine samples.

  20. Transition metal modified and partially calcined inorganic-organic pillared clays for the adsorption of salicylic acid, clofibric acid, carbamazepine, and caffeine from water.

    Science.gov (United States)

    Cabrera-Lafaurie, Wilman A; Román, Félix R; Hernández-Maldonado, Arturo J

    2012-11-15

    Pharmaceutical and Personal Care Products (PPCPs) are considered emerging contaminants, and their efficient removal from water is going to be a challenging endeavor. Microporous adsorbent materials, including pillared clays, could offer a potential solution if tailored properly. Although pillared clays have been employed previously for the removal of organics, the effective removal of PPCPs will only be possible if their surface and textural properties are manipulated from the bottom-up. This work presents the use of modified inorganic-organic pillared clays (IOCs) for the adsorption of salicylic acid, clofibric acid, carbamazepine, and caffeine. The IOCs have been modified with Co(2+), Cu(2+), or Ni(2+) to induce complexation-like adsorbate-adsorbent interactions at ambient conditions, in an attempt to provide an efficient and yet reversible driving force in the sub-ppm concentration range. Furthermore, the IOCs were partially calcined to increase effective surface area by an order of magnitude while preserving some hydrophobicity. In general, the Ni(2+) IOCs exhibited the greatest interaction with salicylic and clofibric acids, respectively, while the Co(2+) adsorbents excelled at adsorbing caffeine at low concentrations. All of the metal-modified IOCs showed comparable adsorption capacities for the case of carbamazepine, probably due to the lack of availability of particular functional groups in this adsorbate.

  1. An integrated, quality by design (QbD) approach for design, development and optimization of orally disintegrating tablet formulation of carbamazepine.

    Science.gov (United States)

    Mishra, Saurabh M; Rohera, Bhagwan D

    2016-06-27

    The objective of the present study was to design and develop a formulation for orally disintegrating tablets (ODTs) of carbamazepine using quality by design principles. The target product profile (TPP) and quality target product profile (QTPP) of ODTs were identified. Risk assessment was carried out by leveraging prior knowledge and experience to define the criticality of factors based on their impact by Ishikawa fishbone diagram and preliminary hazard analysis tool. Box-Behnken response surface methodology was used to study the effect of critical factors on various attributes of ODTs. The independent factors selected were compression pressure (X1), concentration of sublimating agent (volatile material) (X2), disintegrant concentration (X3) and the responses were tablet crushing strength, tablet porosity, disintegration time, water absorption time, tablet friability and drug dissolution. ANOVA and lack of fit test illustrated that selected independent variables had significant effect on the response variables, and excellent correlation was observed between actual and predicted values. Optimization by desirability function indicated that compression pressure, X1 (1534 lbs), ammonium bicarbonate concentration, X2 (7.68%) and Kollidon(®) CL-SF concentration, X3 (6%) were optimum to prepare ODT formulation of carbamazepine of desired attributes complying with QTPP. Thus, in the present study, a high level of assurance was established for ODT product quality and performance.

  2. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  3. 卡马西平对斑马鱼胚胎心脏功能的影响%The Effect of Carbamazepine on Cardiac Function of Zebrafish Embryo

    Institute of Scientific and Technical Information of China (English)

    王雪; 王希敏; 韩利文; 刘可春; 何秋霞; 彭维兵

    2012-01-01

    Objective To explore the feasibility of studying drug toxic and side effect with zebrafish embryos as model. Methods Fourty-eight hours post-fertilization zebrafish embryos were treated with various concentrations of carbamazepine for 24 h. Morphological changes of embryos hearts were observed and heart rate was counted at 8, 16, 24 h after treatment. Then embryos were transferred into embryo medium and the heart rate was observed at 4, 8, 24 h after treatment interruption. Results The heart rate decreased significantly after treatment with carbamazepine for 24 h and showed a good dose-effect relationship with the drug concentration. The 24 h ECso of decrease of heart rate was about 626.07 mmol/L. Heart rate recovered quickly 8h after treatment interruption. Conclusion Carbamazepine lowered the heart rate of zebrafish embryo in a dose-dependent manner and the repression on cardiac function was reversible.%目的 探讨以斑马鱼为动物模型进行药物毒性作用研究的可行性.方法 用不同浓度卡马西平处理发育48 h斑马鱼胚胎,于药物处理后8h、16h、24 h观察各组胚胎心脏形态变化,并计数心率.药物处理24 h后终止药物作用,并于4h、8h、24 h连续观察各组胚胎心率的恢复情况.结果 卡马西平处理引起斑马鱼胚胎心率降低,随处理时间延长和药物浓度升高下降越明显,卡马西平引起胚胎心率下降的24h EC50约为626.07 mmol/L,终止药物作用后8h,胚胎心率恢复至正常水平.结论 卡马西平引起斑马鱼胚胎心率降低,并呈现量效依赖性,卡马西平对心率的抑制具有可逆性.

  4. High doses of carbamazepine for refractory partial epilepsy Altas doses de carbamazepina para epilepsia parcial refratária

    Directory of Open Access Journals (Sweden)

    Cristiana Borges Pereira

    1996-03-01

    Full Text Available Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ. Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1. Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6. Seizure's control was observed in 7 (14.48% patients taking 1200 mg/day and in 2 (4.16% patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%. Ten patients (20.81% had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.Foram analisados 48 pacientes epilépticos com crises parciais que faziam uso de carbamazepina (CBZ em doses iguais ou superiores a 1200 mg por dia. Trinta e três estavam em monoterapia e 15 em politerapia. As outras medicações foram mantidas constantes durante a manipulação da dose de CBZ nos pacientes em politerapia. O critério utilizado para o aumento da dose de CBZ foi a falta de controle clínico e a ausência de efeitos colaterais (independente da dosagem sérica. A dose máxima variou de 1200 a 1900 mg/dia (1200 mg, n=18; 1300 mg/dia, n=1; 1400 mg/dia, n=7; 1600 mg/dia, n=9; 1700 mg/dia, n=4; 1800 mg/dia, n=8 ; 1900 mg/dia, n=1. Dosagens séricas de anticonvulsivantes eram utilizadas no sentido de confirmar a aderência ao tratamento. A média das dosagens disponíveis foi de 9,6 ug/mL. O tempo de seguimento variou de 3 a 96 meses (M=25

  5. Simultaneous Detection of Sulfamethoxazole, Diclofenac, Carbamazepine, and Bezafibrate by Solid Phase Extraction and High Performance Liquid Chromatography with Diode Array Detection

    Science.gov (United States)

    Zhou, Z.; Jiang, J.-Q.

    2014-05-01

    A method of solid phase extraction (SPE) coupled with high performance liquid chromatography and diode array detection (HPLC-DAD) was studied for the simultaneous determination of sulfamethoxazole (SMX), diclofenac (DCF), carbamazepine (CBZ), and bezafi brate (BZF) in test solutions. The target compounds were extracted by SPE from samples, and the resulting elutes were analyzed using a HPLC-DAD system at wavelengths of 270, 280, 290, and 230 nm for SMX, DCF, CBZ, and BZF, respectively. This method shows good recoveries for SMX, DCF, CBZ, and BZF with mean recoveries of 89.7 ± 9.3%, 86.1 ± 7.6%, 95.0 ± 6.5%, and 94.0 ± 5.4%, respectively.

  6. The HLA-B*15:02 allele in a Spanish Romani patient with carbamazepine-induced Stevens-Johnson syndrome.

    Science.gov (United States)

    Bellón, Teresa; Ramírez, Elena; Borobia, Alberto M; Lerma, Victoria; Moreno-Hidalgo, Miguel A; Laosa, Olga; Aramburu, José A; González-Herrada, Carlos; de Abajo, Francisco J

    2016-04-01

    The HLA-B*15:02 allele is a risk factor for carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in populations where the allele is prevalent. Han Chinese and Thai patients are advised to take a genetic test before introducing CBZ. Such testing is not recommended for patients of European descent. We report the case of a Spanish Romani patient who developed Stevens-Johnson syndrome upon treatment with CBZ. In vitro assays confirmed CBZ as the culprit drug. HLA typing showed that the patient carried the HLA-B*15:02 allele. A public database search revealed that 2% of Spanish Romani people likely carry the risk variant HLA-B*15:02 and therefore may be included in the population to be tested prior to beginning treatment with CBZ.

  7. Therapeutic drug monitoring of carbamazepine and its metabolite in children from dried blood spots using liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Shokry, Engy; Villanelli, Fabio; Malvagia, Sabrina; Rosati, Anna; Forni, Giulia; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria; Guerrini, Renzo; la Marca, Giancarlo

    2015-05-10

    Carbamazepine (CBZ) is a first-line drug for the treatment of different forms of epilepsy and the first choice drug for trigeminal neuralgia. CBZ is metabolized in the liver by oxidation into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent and known to contribute to the pharmacological activity of CBZ. The aim of the present study was to develop and validate a reliable, selective and sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of CBZ and its active metabolite in dried blood spots (DBS). The extraction process was carried out from DBS using methanol-water-formic acid (80:20:0.1, v/v/v). Chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50mL/min. The method was linear over the range 1-40mg/L and 0.25-20mg/L for CBZ and CBZE, respectively. The limit of quantification was 0.75mg/L and 0.25mg/L for CBZ and CBZE. Intra-day and inter-day assay precisions were found to be lower than 5.13%, 6.46% and 11.76%, 4.72% with mean percentage accuracies of 102.1%, 97.5% and 99.2%, 97.8% for CBZ and CBZE. We successfully applied the method for determining DBS finger-prick samples in paediatric patients and confirmed the results with concentrations measured in matched plasma samples. This novel approach allows quantification of CBZ and its metabolite from only one 3.2mm DBS disc by LC-MS/MS thus combining advantages of DBS technique and LC-MS/MS in clinical practice.

  8. Dissipation of triclosan, triclocarban, carbamazepine and naproxen in agricultural soil following surface or sub-surface application of dewatered municipal biosolids

    Energy Technology Data Exchange (ETDEWEB)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne [Agriculture and Agri-Food Canada, London, ON N5V 4T3 (Canada); Lapen, David R. [Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6 (Canada); Topp, Edward, E-mail: ed.topp@agr.gc.ca [Agriculture and Agri-Food Canada, London, ON N5V 4T3 (Canada); Department of Biology, Western University, London, ON N6A 5B7 (Canada)

    2015-04-15

    In many jurisdictions land application of municipal biosolids is a valued source of nutrients for crop production. The practice must be managed to ensure that crops and adjacent water are not subject to contamination by pharmaceuticals or other organic contaminants. The broad spectrum antimicrobial agents triclosan (TCS) and triclocarban (TCC), the anti-epileptic drug carbamazepine (CBZ), and the nonsteroidal anti-inflammatory drug naproxen (NAP) are widely used and are carried in biosolids. In the present study, the effect of biosolids and depth of placement in the soil profile on the rates of TCS, TCC, CBZ, and NAP dissipation were evaluated under semi-field conditions. Aggregates of dewatered municipal biosolids (DMBs) supplemented with {sup 14}C-labeled residues were applied either on the soil surface or in the subsurface of the soil profile, and incubated over several months under ambient outdoor conditions. The dissipation of TCS, TCC and NAP was significantly faster in sub-surface than surface applied biosolid aggregates. In contrast the dissipation rate for CBZ was the same in surface applied and incorporated aggregates. Overall, the present study has determined a significant effect of depth of placement on the dissipation rate of biodegradable molecules. - Highlights: • We characterized the soil fate of four organic contaminants carried in biosolids. • Biosolids were placed on the soil surface or incorporated within the soil profile. • Naproxen, triclosan and triclocarban were dissipated more rapidly when incorporated. • Depth of placement did not influence the rate of carbamazepine dissipation. • Soil incorporation of biosolids will result in more rapid dissipation of contaminants.

  9. Photocatalytic degradation of carbamazepine in wastewater by using a new class of whey-stabilized nanocrystalline TiO2 and ZnO.

    Science.gov (United States)

    Mohapatra, D P; Brar, S K; Daghrir, R; Tyagi, R D; Picard, P; Surampalli, R Y; Drogui, P

    2014-07-01

    Nanoscale photocatalysts have attracted much attention due to their high surface area to volume ratios. However, due to extremely high reactivity, TiO2 and ZnO nanoparticles prepared using different methods tend to either react with surrounding media or agglomerate, resulting in the formation of much larger flocs and significant loss in reactivity. This work investigates the photocatalytic degradation of carbamazepine (CBZ), a persistent pharmaceutical compound from wastewater (WW) using TiO2 and ZnO nanoparticles prepared in the presence of a water-soluble whey powder as stabilizer. The TiO2 and ZnO nanoparticles prepared in the presence of whey stabilizer displayed much less agglomeration and greater degradation power than those prepared without a stabilizer. Higher photocatalytic degradation of carbamazepine was observed (100%) by using whey stabilized TiO2 nanoparticles with 55 min irradiation time as compared to ZnO nanoparticles (92%). The higher degradation of CBZ in wastewater by using TiO2 nanoparticles as compared to ZnO nanoparticles was due to formation of higher photo-generated holes with high oxidizing power of TiO2. The photocatalytic capacity of ZnO anticipated as similar to that of TiO2 as it has the same band gap energy (3.2 eV) as TiO2. However, in the case of ZnO, photocorrosion frequently occurs with the illumination of UV light and this phenomenon is considered as one of the main reasons for the decrease of ZnO photocatalytic activity in aqueous solutions. Further, the estrogenic activity of photocatalyzed WW sample with CBZ and its by-products was carried out by yeast estrogen screen (YES) assay method. Based upon the YES test results, none of the samples showed estrogenic activity.

  10. Efficacy and tolerability of carbamazepine for the treatment of painful diabetic neuropathy in adults: a 12-week, open-label, multicenter study

    Directory of Open Access Journals (Sweden)

    Saeed T

    2014-07-01

    Full Text Available Tariq Saeed,1 Muhammad Nasrullah,2 Adnan Ghafoor,3 Riaz Shahid,4 Nadeem Islam,5 Mohammad Usman Khattak,6 Neeta Maheshwary,7 Ahson Siddiqi,7 Muhammad Athar Khan81Pakistan Telecommunication Company Ltd, Karachi, Pakistan; 2Cavalary Hospital, Gulberg, Lahore, Pakistan; 3Fauji Foundation Hospital, Rawalpindi, Pakistan; 4Dr Riaz Shahid Clinic, Peshawar Cantt, Peshawar, Pakistan; 5Punjab Employs Social Security Institution, Islamabad, Pakistan; 6Medical B Unit, Hayat Abad Medical Complex, Peshawar, Pakistan; 7Novartis Pharma Pakistan, Karachi, Pakistan; 8Department of Medical Education, King Saud bin Abdulaziz University, Riyadh, Kingdom of Saudi ArabiaObjective: Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan.Methods: This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18–65 years suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ≥4. Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale–Short Form (pain severity score and pain interference score. QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs and serious AEs.Results: Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD] pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001. The mean (± SD pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001. There was a decrease of ≥30% in the pain severity score between visits. The mean (± SD QoL scale score improved from 5.9±1

  11. Efficacy and tolerability of carbamazepine for the treatment of painful diabetic neuropathy in adults: a 12-week, open-label, multicenter study

    Science.gov (United States)

    Saeed, Tariq; Nasrullah, Muhammad; Ghafoor, Adnan; Shahid, Riaz; Islam, Nadeem; Khattak, Mohammad Usman; Maheshwary, Neeta; Siddiqi, Ahson; Khan, Muhammad Athar

    2014-01-01

    Objective Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL) of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan. Methods This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18–65 years) suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ≥4). Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale–Short Form (pain severity score and pain interference score). QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs) and serious AEs. Results Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD]) pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001). The mean (± SD) pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001). There was a decrease of ≥30% in the pain severity score between visits. The mean (± SD) QoL scale score improved from 5.9±1.6 at baseline to 8.0±1.7 at week 12. A total of ten (2.2%) patients reported AEs during the study period. No patient discontinued the study due to AEs. Conclusion In this real-life experience study, carbamazepine, when prescribed for 12 weeks to adult diabetic patients suffering from neuropathic pain, showed pain-relief effect, with reduced mean pain severity and mean pain interference scores and with improved QoL and good tolerability profile. PMID:25061334

  12. Effects of pharmaceutical micropollutants on the membrane fouling of a submerged MBR treating municipal wastewater: case of continuous pollution by carbamazepine.

    Science.gov (United States)

    Li, Chengcheng; Cabassud, Corinne; Reboul, Bernard; Guigui, Christelle

    2015-02-01

    Membrane bioreactor (MBR) is increasingly used for municipal wastewater treatment and reuse and great concerns have been raised to some emerging trace pollutants found in aquatic environment in the last decade, notably the pharmaceuticals. As a consequence the removal of pharmaceutical micropollutants by MBRs has been extensively investigated. But there is still a lack of knowledge on the effects of the current presence of pharmaceutical micropollutants in domestic wastewaters on MBR fouling. Among the different pharmaceuticals, it was decided to focus on carbamazepine (CBZ), an anti-epileptic drug, because of its occurrence in domestic wastewaters and persistency in biological processes including MBRs. This paper focuses on the effects of continuous carbamazepine pollution on MBR fouling. A continuous introduction of CBZ into the MBR via the feed (about 90 μg L(-1) CBZ in the feed) provoked a TMP jump. It occurred just 1 day after the addition of CBZ in MBR and a significantly higher increase rate of TMP was also observed after 1 day after addition of CBZ in MBR, as compared to that before addition of CBZ. This indicates that the pharmaceutical stress induced by CBZ causes more severe membrane fouling. Addition of CBZ was shown to induce a significant increase of the concentration of proteins in the supernatant at the beginning several days then stabilized to original level whereas no significant change was found for polysaccharides. HPLC-SEC analysis showed that addition of CBZ induced a decrease of 100-1000 kDa protein-like SMPs and a more significant increase of 10-100 kDa protein-like SMPs in the supernatant. Moreover it was found that addition of CBZ in the MBR affected the sludge microbial activities, as a slight inhibition (about 20%) of the exogenous respiration rate was observed. The increased membrane fouling could be related to the change in biomass characteristics and supernatant quality after addition of CBZ in MBR. This study allows also

  13. Hydrothermal Synthesis of Hydrangea-Like F-Doped Titania Microspheres for the Photocatalytic Degradation of Carbamazepine under UV and Visible Light Irradiation

    Directory of Open Access Journals (Sweden)

    Miaomiao Ye

    2012-01-01

    Full Text Available Hydrangea-like F-doped TiO2 microspheres have been synthesized on a large scale by a simple hydrothermal process using potassium titanium oxalate as the titanium source, ammonium fluoride and hydrogen peroxide as the etchant. The photocatalytic activities were evaluated using carbamazepine as the target organic molecule under UV and visible light irradiation. Structural characterization indicates that the hydrangea-like TiO2 microspheres, with an average diameter of 2.80 μm, are composed of numerous anatase TiO2 petals. Moreover, it is found that both the NH4F and H2O2 dosages have important effects on the formation of the hydrangea-like structures. In addition, photocatalytic experiments show that the hydrangea-like TiO2 microspheres calcined at 500°C exhibit high photocatalytic efficiency under both UV and visible light irradiation. The enhanced photocatalytic activity can be attributed to the successful fluorine doping, good crystallinity, and the unique nanostructures.

  14. Removal of Carbamazepine from Water by a Novel TiO2-Coconut Shell Powder/UV Process: Composite Preparation and Photocatalytic Activity.

    Science.gov (United States)

    Khraisheh, Majeda; Kim, Jongkyu; Campos, Luiza; Al-Muhtaseb, Ala'a H; Walker, Gavin M; Alghouti, Mohammad

    2013-09-01

    A novel TiO2-coconut shell powder (TCNSP) composite, prepared by the controlled sol-gel method with a subsequent heat treatment, was investigated as an innovative photocatalytic absorbent for the removal of carbamazepine (CBZ). CBZ is used worldwide as an antiepileptic drug, which has recently been recognized as an important organic pollutant increasingly found in wastewaters from urban areas and other aquatic environments. The granulation process was performed by using a semiautomated mass production line to produce sufficient quantities of TCNSP composites, possessing sufficient crush strength for commercialization. Physical properties of the TCNSP composite such as crystallinity, morphology, crush strength, and the Brunauer-Emmett-Teller (BET)-specific surface area were controlled by the mass ratio of titanium dioxide sol and coconut shell powder (CNSP). Calcination at 700°C produced anatase phase TiO2 in the TCNSP composites with a BET high surface area of 454 m(2)/g. Anatase crystallite size of the TCNSP composite increased from 2.37 to 15.11 nm with increasing calcination temperature from 500°C to 800°C. Calcinated TCNSP composites had higher CBZ removal efficiency (98%) than pure TiO2 (23%) and CNSP (34%) within a 40-min reaction time. Optimization of this innovative adsorption/photocatalytic process was obtained by a response surface methodology and a central composite design model, which indicated that this novel and sustainable technology was successful in removing CBZ from a solution.

  15. Electrochemistry Combined with LC-HRMS: Elucidating Transformation Products of the Recalcitrant Pharmaceutical Compound Carbamazepine Generated by the White-Rot Fungus Pleurotus ostreatus.

    Science.gov (United States)

    Seiwert, Bettina; Golan-Rozen, Naama; Weidauer, Cindy; Riemenschneider, Christina; Chefetz, Benny; Hadar, Yitzhak; Reemtsma, Thorsten

    2015-10-20

    Transformation products (TPs) of environmental pollutants must be identified to understand biodegradation processes and reaction mechanisms and to assess the efficiency of treatment processes. The combination of oxidation by an electrochemical cell (EC) with analysis by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) is a rapid approach for the determination and identification of TPs generated by natural microbial processes. Electrochemically generated TPs of the recalcitrant pharmaceutical carbamazepine (CBZ) were used for a target screening for TPs formed by the white-rot fungus Pleurotus ostreatus. EC with LC-HRMS facilitates detection and identification of TPs because the product spectrum is not superimposed with biogenic metabolites and elevated substrate concentrations can be used. A group of 10 TPs formed in the microbial process were detected by target screening for molecular ions, and another 4 were detected by screening on the basis of characteristic fragment ions. Three of these TPs have never been reported before. For CBZ, EC with LC-HRMS was found to be more effective than software tools in defining targets for the screening and faster than nontarget screening alone in TP identification. EC with LC-HRMS may be used to feed MS databases with spectra of possible TPs of larger numbers of environmental contaminants for an efficient target screening.

  16. Carbamazepine in municipal wastewater and wastewater sludge: ultrafast quantification by laser diode thermal desorption-atmospheric pressure chemical ionization coupled with tandem mass spectrometry.

    Science.gov (United States)

    Mohapatra, D P; Brar, S K; Tyagi, R D; Picard, P; Surampalli, R Y

    2012-09-15

    In this study, the distribution of the anti-epileptic drug carbamazepine (CBZ) in wastewater (WW) and aqueous and solid phases of wastewater sludge (WWS) was carried out. A rapid and reliable method enabling high-throughput sample analysis for quicker data generation, detection, and monitoring of CBZ in WW and WWS was developed and validated. The ultrafast method (15s per sample) is based on the laser diode thermal desorption-atmospheric pressure chemical ionization (LDTD-APCI) coupled to tandem mass spectrometry (MS/MS). The optimization of instrumental parameters and method application for environmental analysis are presented. The performance of the novel method was evaluated by estimation of extraction recovery, linearity, precision and detection limit. The method detection limits was 12 ng L(-1) in WW and 3.4 ng g(-1) in WWS. The intra- and inter-day precisions were 8% and 11% in WW and 6% and 9% in WWS, respectively. Furthermore, three extraction methods, ultrasonic extraction (USE), microwave-assisted extraction (MAE) and accelerated solvent extraction (ASE) with three different solvent condition such as methanol, acetone and acetonitrile:ethyle acetate (5:1, v/v) were compared on the basis of procedural blank and method recovery. Overall, ASE showed the best extraction efficiency with methanol as compared to USE and MAE. Furthermore, the quantification of CBZ in WW and WWS samples showed the presence of contaminant in all stages of the treatment plant.

  17. Validated spectrofluorimetric method for the determination of carbamazepine in pharmaceutical dosage forms after reaction with 4-chloro-7--nitrobenzo-2-oxa-1,3-diazole (NBD-Cl).

    Science.gov (United States)

    Walash, Mohammed I; El-Enany, Nahed; Askar, Hanany

    2015-11-01

    A sensitive and simple spectrofluorimetric method has been developed and validated for the determination of the anti-epileptic drug carbamazepine (CBZ) in its dosage forms. The method was based on a nucleophilic substitution reaction of CBZ with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in borate buffer (pH 9) to form a highly fluorescent derivative that was measured at 530 nm after excitation at 460 nm. Factors affecting the formation of the reaction product were studied and optimized, and the reaction mechanism was postulated. The fluorescence-concentration plot is rectilinear over the range of 0.6-8 µg/mL with limit of detection of 0.06 µg/mL and limit of quantitation of 0.19 µg/mL. The method was applied to the analysis of commercial tablets and the results were in good agreement with those obtained using the reference method. Validation of the analytical procedures was evaluated according to ICH guidelines.

  18. Adaptation of microvolume EMIT assays for theophylline, phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, and gentamicin to a CentrifiChem chemistry analyzer.

    Science.gov (United States)

    Studts, D; Haven, G T; Kiser, E J

    1983-01-01

    We have developed microvolume EMIT procedures for theophylline, phenobarbital, phenytoin, carbamazepine, primidone, ethosuximide, and gentamicin using a centrifugal analyzer (CentrifiChem and Pipettor 1000) to reduce the manufacturer's recommended manual reagent consumption by one-sixth. In addition to developing the EMIT procedure, the performance of the analyzer and pipettor were verified. The analyzer and pipettor are capable of producing within-run precision at a 3-microliters sample volume and 210-microliters analyzer cuvette volume equal to or less than 1.5%. The performance of the EMIT procedures on the analyzer yielded spike drug recoveries of 90.8 to 106.1% for drug concentrations throughout the calibration concentration range of each assay. The percent error on standard reference material of the National Bureau of Standards ranged from a +12.0% to a -0.6% for ethosuximide, phenobarbital, phenytoin, and primidone. Patient comparison data yielded slopes from 0.930 to 1.110 for all assays. The other important feature of the adapted EMIT assay is its simplicity for use on a routine basis.

  19. The impacts of pharmaceutical drugs under ocean acidification: New data on single and combined long-term effects of carbamazepine on Scrobicularia plana.

    Science.gov (United States)

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Figueira, Etelvina; Soares, Amadeu M V M

    2016-01-15

    Ocean acidification and increasing discharges of pharmaceutical contaminants into aquatic systems are among key and/or emerging drivers of environmental change affecting marine ecosystems. A growing body of evidence demonstrates that ocean acidification can have direct and indirect impacts on marine organisms although combined effects with other stressors, namely with pharmaceuticals, have received very little attention to date. The present study aimed to evaluate the impacts of the pharmaceutical drug Carbamazepine and pH 7.1, acting alone and in combination, on the clam Scrobicularia plana. For this, a long-term exposure (28 days)was conducted and a set of oxidative stress markers was investigated. The results obtained showed that S. plana was able to develop mechanisms to prevent oxidative damage when under low pH for a long period, presenting higher survival when exposed to this stressor compared to CBZ or the combination of CBZ with pH 7.1. Furthermore, the toxicity of CBZ on S. plana was synergistically increased under ocean acidification conditions (CBZ + pH 7.1): specimens survival was reduced and oxidative stress was enhanced when compared to single exposures. These findings add to the growing body of evidence that ocean acidification will act to increase the toxicity of CBZ to marine organisms,which has clear implications for coastal benthic ecosystems suffering chronic pollution from pharmaceutical drugs.

  20. The use of O, H and Sr isotopes and carbamazepine to identify the origin of water bodies supplying a shallow alluvial aquifer

    Science.gov (United States)

    Sassine, Lara; Le Gal La Salle, Corinne; Lancelot, Joël; Verdoux, Patrick

    2014-05-01

    Alluvial aquifers are of great socio-economic importance in France since they supply 82% of drinking water production, though they reveal to be very vulnerable to pesticides and emerging organic contaminants. The aim of this work is to identify the origin of water bodies which contribute to the recharge of an alluvial aquifer for a better understanding of its hydrochemistry and transfer of contaminants therein. The study is based on an isotopic and geochemical tracers approach, including major elements, trace elements (Br, Sr),and isotopes (δ18O, δ2H, 87Sr/86Sr), as well as organic molecules. Indeed, organic molecules such as pharmaceutical compounds, more precisely carbamazepine and caffeine, have shown their use as indicators of surface water in groundwater. The study area is a partially-confined shallow alluvial aquifer, the so-called Vistrenque aquifer, located at 15 km from the Mediterranean Sea, in the Quaternary alluviums deposited by an ancient arm of the Rhône River, in Southern France. This aquifer constitutes a shallow alluvial layer in a NE-SW graben structure. It is situated between a karst aquifer in lower Cretaceous limestones, on the NW border, and the Costières Plateau, on the SE border, having a similar geology as the Vistrenque. The alluvial plain is crossed by a surface water network with the Vistre as the main stream, and a canal used for irrigation essentially, the BRL canal, which is fed by the Rhône River. δ18O and δ2H allowed to differentiate the BRL canal water, depleted in heavy isotopes (δ2H = -71.5o vs V-SMOW), and the more enriched local rainwater (δ2H = -35.5o vs V-SMOW). In the Vistre surface water a binary mixing were evidenced with the BRL canal water and the rainwater, as end members. Then, in the Vistrenque groundwater both the BRL and the Vistre contributions could be identified, as they still show contrasting signature with local recharge. This allows to highlight the surface water contribution to a heavily exploited

  1. Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Hadjira Rabti

    2014-06-01

    Full Text Available Elementary osmotic pump (EOP is a unique extended release (ER drug delivery system based on the principle of osmosis. It has the ability to minimize the amount of the drug, accumulation and fluctuation in drug level during chronic uses. Carbamazepine (CBZ, a poorly water-soluble antiepileptic drug, has serious side effects on overdoses and chronic uses. The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance. Firstly, a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug. Then, designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance (ANOVA, respectively. The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone (PVP K30 and sodium lauryl sulfate (SLS. The plasticizer amount and molecular weight (MW together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane (SPM thickness inversely influence the release rate. In addition, the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core. Further, orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm. In this study we report the successful formulation of CBZ-EOP tablets, which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80% of CBZ at a rate of approximately zero order for up to 12 h.

  2. Impact of water quality on removal of carbamazepine in natural waters by N-doped TiO{sub 2} photo-catalytic thin film surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Avisar, Dror, E-mail: drorvi@post.tau.ac.il [The Hydro-Chemistry Laboratory, Faculty of Geography and the Environment, Tel Aviv University, Tel Aviv 69978 (Israel); Horovitz, Inna [The Hydro-Chemistry Laboratory, Faculty of Geography and the Environment, Tel Aviv University, Tel Aviv 69978 (Israel); School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); Lozzi, Luca; Ruggieri, Fabrizio [Department of Physical and Chemical Sciences, University of L’Aquila, Via Vetoio, I-67010 Coppito, L’Aquila (Italy); Baker, Mark; Abel, Marie-Laure [The Surface Analysis Laboratory, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom); Mamane, Hadas [School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel)

    2013-01-15

    Highlights: ► N-doped TiO{sub 2} thin films have been deposited by sol–gel dip-coating. ► CBZ removal improved with increasing medium pH in the range of 5–9. ► DOC at a concentration of 5 mg/L resulted in an ∼20% reduction in CBZ removal. ► Alkalinity values of 100 mg/L as CaCO{sub 3} resulted in a 40% decrease in CBZ removal. ► Complete suppression of the photocatalytic process in wastewater effluent. -- Abstract: Photocatalytic experiments on the pharmaceutical pollutant carbamazepine (CBZ) were conducted using sol–gel nitrogen-doped TiO{sub 2}-coated glass slides under a solar simulator. CBZ was stable to photodegradation under direct solar irradiation. No CBZ sorption to the catalyst surface was observed, as further confirmed by surface characterization using X-ray photoelectron spectroscopic analysis of N-doped TiO{sub 2} surfaces. When exposing the catalyst surface to natural organic matter (NOM), an excess amount of carbon was detected relative to controls, which is consistent with NOM remaining on the catalyst surface. The catalyst surface charge was negative at pH values from 4 to 10 and decreased with increasing pH, correlated with enhanced CBZ removal with increasing medium pH in the range of 5–9. A dissolved organic carbon concentration of 5 mg/L resulted in ∼20% reduction in CBZ removal, probably due to competitive inhibition of the photocatalytic degradation of CBZ. At alkalinity values corresponding to CaCO{sub 3} addition at 100 mg/L, an over 40% decrease in CBZ removal was observed. A 35% reduction in CBZ occurred in the presence of surface water compared to complete suppression of the photocatalytic process in wastewater effluent.

  3. Anhydrate to hydrate solid-state transformations of carbamazepine and nitrofurantoin in biorelevant media studied in situ using time-resolved synchrotron X-ray diffraction.

    Science.gov (United States)

    Boetker, Johan P; Rantanen, Jukka; Arnfast, Lærke; Doreth, Maria; Raijada, Dhara; Loebmann, Korbinian; Madsen, Cecilie; Khan, Jamal; Rades, Thomas; Müllertz, Anette; Hawley, Adrian; Thomas, Diana; Boyd, Ben J

    2016-03-01

    Transformation of the solid-state form of a drug compound in the lumen of the gastrointestinal tract may alter the drug bioavailability and in extreme cases result in patient fatalities. The solution-mediated anhydrate-to-hydrate phase transformation was examined using an in vitro model with different biorelevant media, simulated fasted and fed state intestinal fluids containing bile salt and dioleoylphosphatidylcholine (DOPC) micelles, DOPC/sodium dodecyl sulfate (SDS) mixture, bile salt solution and water. Two anhydrate compounds (carbamazepine, CBZ and nitrofurantoin, NF) with different overall transformation time into hydrate form were used as model compounds. The transformations were monitored using direct structural information from time-resolved synchrotron X-ray diffraction. The kinetics of these transformations were estimated using multivariate data analysis (principal component analysis, PCA) and compared to those for nitrofurantoin (NF). The study showed that the solution-mediated phase transformation of CBZ anhydrate was remarkably faster in the DOPC/SDS medium compared to transformation in all the other aqueous dispersion media. The conversion time for CBZ anhydrate in water was shorter than for DOPC/SDS but still faster than the conversion seen in fed and fasted state micellar media. The conversion of CBZ anhydrate to hydrate was the slowest in the solution containing bile salt alone. In contrast, the solution-mediated phase transformations of NF did only show limited kinetic dependence on the dispersion media used, indicating the complexity of the nucleation process. Furthermore, when the CBZ and NF material was compacted into tablets the transformation times were remarkably slower. Results suggest that variations in the composition of the contents of the stomach/gut may affect the recrystallization kinetics, especially when investigating compounds with relatively fast overall transformation time, such as CBZ.

  4. Biphasic characteristic of interactions between stiripentol and carbamazepine in the mouse maximal electroshock-induced seizure model: a three-dimensional isobolographic analysis.

    Science.gov (United States)

    Luszczki, Jarogniew J; Czuczwar, Stanislaw J

    2006-10-01

    The anticonvulsant effects produced by stiripentol (STP), carbamazepine (CBZ), and their combination in the maximal electroshock (MES)-induced seizures in mice were investigated using three-dimensional (3D) isobolographic analysis. With 3D isobolography, the combinations of both drugs at the fixed-ratios of 1:3, 1:1, and 3:1 for 16%, 50% and 84% antiseizure effects, respectively, were examined in order to evaluate the preclinical characteristics of the interactions between STP and CBZ. Additionally, to characterize precisely the types of interactions observed in the MES test, free plasma and total brain CBZ concentrations were estimated for all fixed-ratios tested. The 3D isobolographic analysis showed that STP and CBZ combined at the fixed-ratio of 1:3 produced supra-additive (synergistic) interactions in the MES test for the anticonvulsant effects ranging between 16% and 84%. In contrast, the combination of STP with CBZ at the fixed-ratio of 3:1 exerted sub-additive (antagonistic) interactions in 3D isobolography for all antiseizure effects examined in the MES test. Only the combination of STP and CBZ at the fixed-ratio of 1:1 was additive for the investigated effects (16%, 50% and 84%) in 3D isobolography. Pharmacokinetic evaluation of CBZ concentrations revealed that STP increased both free plasma and total brain CBZ concentrations for all fixed-ratio combinations tested (1:3, 1:1 and 3:1). In conclusion, the 3D isobolographic findings suggest that the combination of STP with CBZ exerted biphasic characteristics of interactions in the MES test, despite the pharmacokinetic increase in CBZ content in plasma and brains of experimental animals.

  5. Concurrent cooperativity and substrate inhibition in the epoxidation of carbamazepine by cytochrome P450 3A4 active site mutants inspired by molecular dynamics simulations.

    Science.gov (United States)

    Müller, Christian S; Knehans, Tim; Davydov, Dmitri R; Bounds, Patricia L; von Mandach, Ursula; Halpert, James R; Caflisch, Amedeo; Koppenol, Willem H

    2015-01-27

    Cytochrome P450 3A4 (CYP3A4) is the major human P450 responsible for the metabolism of carbamazepine (CBZ). To explore the mechanisms of interactions of CYP3A4 with this anticonvulsive drug, we carried out multiple molecular dynamics (MD) simulations, starting with the complex of CYP3A4 manually docked with CBZ. On the basis of these simulations, we engineered CYP3A4 mutants I369F, I369L, A370V, and A370L, in which the productive binding orientation was expected to be stabilized, thus leading to increased turnover of CBZ to the 10,11-epoxide product. In addition, we generated CYP3A4 mutant S119A as a control construct with putative destabilization of the productive binding pose. Evaluation of the kinetics profiles of CBZ epoxidation demonstrate that CYP3A4-containing bacterial membranes (bactosomes) as well as purified CYP3A4 (wild-type and mutants I369L/F) exhibit substrate inhibition in reconstituted systems. In contrast, mutants S119A and A370V/L exhibit S-shaped profiles that are indicative of homotropic cooperativity. MD simulations with two to four CBZ molecules provide evidence that the substrate-binding pocket of CYP3A4 can accommodate more than one molecule of CBZ. Analysis of the kinetics profiles of CBZ metabolism with a model that combines the formalism of the Hill equation with an allowance for substrate inhibition demonstrates that the mechanism of interactions of CBZ with CYP3A4 involves multiple substrate-binding events (most likely three). Despite the retention of the multisite binding mechanism in the mutants, functional manifestations reveal an exquisite sensitivity to even minor structural changes in the binding pocket that are introduced by conservative substitutions such as I369F, I369L, and A370V.

  6. 卡马西平降解菌的筛选分离及其降解机理%Isolation of a bacterial strain capable of carbamazepine degrading and biodegradation mechanism

    Institute of Scientific and Technical Information of China (English)

    杨林; 薛罡; 刘亚男

    2012-01-01

    Quite recently,among new emerging contaminants,pharmaceutical products and their active metabolites are an emerging environmental issue,due to their presence in the aquatic environment and potential for impacts on wildlife and humans.Carbamazepine was one of the most frequently detected pharmaceuticals in surface water and even in drinking water and at the relatively high concentration levels.Moreover,this drug has displayed high chronic ecotoxicity.A strain of carbamazepine-degrading bacterium was isolated from biological aerated filter treating pharmaceutical wastewater.It was identified as Pseudomonas putida YK-6,based on biochemical test,16S rRNA gene sequence analysis.Strain YK-6 could grow in liquid mineral salt medium with carbamazepine as sole source of carbon,nitrogen and energy.HPLC analysis revealed that the carbamazepine degradation rate by YK-6 after 5 days was 54.66% at pH 7.2,30℃,initial carbamazepine concentration of 20 mg/L and oscillation rate of 160 r/min.Possible degradation pathway of carbamazepine by strain YK-6 was the biological oxidation.The CBZ was oxidized into CBZ-EP,and then CBZ-EP was converted to CBZ-DiOH through the hydrolysis.CBZ-DiOH was cracked into aniline and o-benzoic acid through oxidative decarboxylation by pyruvate and under the reducing the role of coenzyme NADH,and then the late one was further oxidized until the final mineralization.%药品污染物日益成为新兴污染物研究的重点,药品卡马西平因具有多种药效被广泛使用,在环境中频繁被检出,且浓度较高,不易去除,通常作为环境中药品污染状况的指示化合物。本研究从长期用于去除药品废水的曝气生物滤池中分离出一株细菌YK-6,其能以卡马西平为惟一碳源、氮源和能源生长,通过生理生化以及16S rDNA基因序列分析鉴定并命名为Pseudomonas putida YK-6。该菌株YK-6在pH为7.2、温度30℃、卡马西平初始浓度为20 mg/L、摇床振荡速率为160 r

  7. Occurrence and fate of the angiotensin II receptor antagonist transformation product valsartan acid in the water cycle--a comparative study with selected β-blockers and the persistent anthropogenic wastewater indicators carbamazepine and acesulfame.

    Science.gov (United States)

    Nödler, Karsten; Hillebrand, Olav; Idzik, Krzysztof; Strathmann, Martin; Schiperski, Ferry; Zirlewagen, Johannes; Licha, Tobias

    2013-11-01

    The substantial transformation of the angiotensin II receptor antagonist valsartan to the transformation product 2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-carboxylic acid (referred to as valsartan acid) during the activated sludge process was demonstrated in the literature and confirmed in the here presented study. However, there was a severe lack of knowledge regarding the occurrence and fate of this compound in surface water and its behavior during drinking water treatment. In this work a comparative study on the occurrence and persistency of valsartan acid, three frequently used β-blockers (metoprolol, atenolol, and sotalol), atenolol acid (one significant transformation product of atenolol and metoprolol), and the two widely distributed persistent anthropogenic wastewater indicators carbamazepine and acesulfame in raw sewage, treated wastewater, surface water, groundwater, and tap water is presented. Median concentrations of valsartan acid in the analyzed matrices were 101, 1,310, 69, treatment plants were confirmed as significant source. Regarding concentration levels of pharmaceutical residues in surface waters valsartan acid was found just as relevant as the analyzed β-blockers and the anticonvulsant carbamazepine. Regarding its persistency in surface waters it was comparable to carbamazepine and acesulfame. Furthermore, removal of valsartan acid during bank filtration was poor, which demonstrated the relevance of this compound for drinking water suppliers. Regarding drinking water treatment (Muelheim Process) the compound was resistant to ozonation but effectively eliminated (≥90%) by subsequent activated carbon filtration. However, without applying activated carbon filtration the compound may enter the drinking water distribution system as it was demonstrated for Berlin tap water.

  8. Treatment with carbamazepine and gabapentin of a patient with primary erythermalgia (erythromelalgia) identified to have a mutation in the SCN9A gene, encoding a voltage-gated sodium channel.

    Science.gov (United States)

    Natkunarajah, J; Atherton, D; Elmslie, F; Mansour, S; Mortimer, P

    2009-12-01

    Primary erythermalgia (erythromelalgia) is a rare autosomal dominant condition characterized by intermittent attacks of erythema, increased skin temperature and severe burning pain in the extremities, in a bilateral symmetrical distribution. Mutations in the SCN9A gene, which encodes a voltage-gated sodium channel have been shown to cause this disease. We report a family identified to have a mutation in the SCN9A gene, in which one severely affected family member has responded to the therapeutic combination of gabapentin and carbamazepine treatment.

  9. 给药后卡马西平大鼠血药浓度测定及其核磁共振代谢组学分析%Determination of serum carbamazepine concentration and metabonomic analysis in rats

    Institute of Scientific and Technical Information of China (English)

    蔡茁; 莫立乾; 关山越; 刘楚阳; 刘韵; 郭丹

    2014-01-01

    目的:采用基于核磁共振(NMR)的代谢组学技术分析卡马西平灌胃后对大鼠血清代谢组的影响。方法24只健康雄性Wistar大鼠,随机分为4组:卡马西平高、中、低剂量组和正常对照组,每组6只。连续灌胃给药7 d后,麻醉后腹主动脉采血,于高效液相色谱仪中检测血清药物浓度,利用核磁共振技术测定血清1H NMR谱,进行模式识别分析,取肝肾组织进行病理学检查。结果卡马西平高、中、低3个剂量组稳态血药浓度分别为14.64±1.41、8.54±1.19、4.56±0.64µg· ml-1,卡马西平高剂量组肝脏有轻微肿胀,各组肾脏组织均无明显病变。血清中丙二胺、去氧皮质酮、脱氢胆固醇、甜菜碱、β-丙氨酸、胱硫醚、4-甲基-2-戊酮酸、肌酸含量下降,糖类、乳酸、琥珀酸、乙酰磷酸、己二酸含量升高。PCA主成分分析表明,给药组和对照组的代谢物存在明显差异,能够被区分开。卡马西平不同剂量组之间,代谢谱无种类的明显差异,只存在代谢物含量高低的不同。结论卡马西平对正常大鼠的代谢过程具有显著影响,这为卡马西平的临床用药监测和用药安全提供了依据。利用NMR技术对药物药效学和毒理学评价具有独特的优势和重要的价值。%Objective To study the effects of carbamazepine on serum metabolic profiles in rats using nuclear magnetic resonance (NMR) spectroscopy. Methods Twenty-four healthy male Wistar rats were randomized into 4 groups (n=6) for daily intragastric administration of high-, medium-or low-dose carbamazepine or distilled water (control) for 7 days. Blood samples were collected from the abdominal aortic under anesthesia after the treatment to determine serum carbamazepine concentration using high-performance liquid chromatography. 1H nuclear magnetic resonance (1H NMR) spectra were acquired for pattern recognition analysis. Histopathological changes of

  10. 探讨卡马西平结合盐酸氟桂利嗪治疗耳鸣的临床疗效%Observation on Clinical Efficacy of Carbamazepine Combined with Flunar-izine Dihydrochloride Treating Tinnitus

    Institute of Scientific and Technical Information of China (English)

    金俊

    2016-01-01

    目的:观察卡马西平结合盐酸氟桂利嗪治疗耳鸣的临床疗效。方法随机选取该院2014年9月—2016年5月收治的60例耳鸣患者作为研究对象,根据治疗的先后顺序分为常规组与研究组,每组30例。常规组患者接受盐酸氟桂利嗪治疗,研究组在常规组的基础上加卡马西平治疗,比较临床治疗效果。结果研究组治疗总有效率达到93.33%,常规组为86.67%,差异有统计学意义(P﹤0.05)。结论卡马西平结合盐酸氟桂利嗪治疗耳鸣,临床治疗显著,减少了不良反应的发生机率,改善了患者的病情。但两种药物联合使用存在一定争议,因此不推荐在临床上推广,疗效仍需要进一步的探讨。%Objective To observe the clinical efficacy of carbamazepine combined with flunarizine dihydrochloride treating tinnitus. Methods Random selected from September 2014 to May 2016 were 60 cases of tinnitus patients as the research object, according to the order of treatment of divided into normal group and the group, each group 30 cases. Regular group of patients treated with flunarizine hydrochloride, the team on the basis of the normal group and carbamazepine treatment, to compare the clinical therapeutic effect. Results The total effective rate of the research group was 93.33%, and that of the conventional group was 86.67%.,which had statistical significance(P﹤0.05). Conclusion Carbamazepine combined with flunarizine dihydrochloride treating tinnitus,reduces the incidence rate of adverse reactions and improves the condition of patients. But there are some different viewpoints for the combination of two medicines, so it is not worthy of clinical promo-tion. And the efficacy needs to be explored.

  11. Determination of Blood Concentration of Carbamazepine in Stevens-Johnson Syndrome by HPLC%Stevens-Johnson综合征患者卡马西平的血药浓度测定

    Institute of Scientific and Technical Information of China (English)

    蔡茁; 郭丹

    2013-01-01

    Objective To adopt the HPLC method to determine the serum concentration of carbamazepine in Stevens-Johnson syndrome.Methods The serum samples were extracted with methanol and dichloromethane for conducting the sample determination.The VP-O DS-C18(250 mm × 4.6 mm,5 μm)was taken as the chromatographic column,the mobile phase was composed of methanol-water (15 ∶ 85)with a flow rate of 1.0 mL/min.The detection wavelength was set at 240 nm.Results The linear range of carbamazepine was 4-20 mg/mL(r=0.999 1,n=5),the relative average recovery rates were 103.12 %,103.77 % and 101.69 %,respectively.Conclusion This method is simple with accurate result and high sensitivity,which can provide the scientific basis for mastering the adverse reactions of carbamazepine in clinic.%目的 采用高效液相色谱法测定Stevens-Johnson综合征患者血清中卡马西平的质量浓度.方法 血清样品采用甲醇和二氯甲烷萃取后进样测定,以VP-ODS C18柱(250 mn×4.6 mm,5μm)为色谱柱,以甲醇-水(15∶85)为流动相,检测波长为240 nm,流速为1.0 mL/min.结果 卡马西平质量浓度在4~ 20 μg/mL范围内与峰面积呈良好线性关系,r=0.999 1(n=5),低、中、高质量浓度的平均相对回收率分别为103.12%,103.77%,101.69%(n=5).结论 该方法简单、结果准确、灵敏度高,可为临床监测卡马西平不良反应提供科学依据.

  12. Comparative study on gabapentin and carbamazepine medication in treatment of Trigeminal Neuralgia%加巴喷丁与卡马西平治疗三叉神经痛的对比分析

    Institute of Scientific and Technical Information of China (English)

    陈忠红

    2015-01-01

    目的:对比分析加巴喷丁与卡马西平对三叉神经痛的治疗效果。方法搜集本院2014年1月~2015年1月三叉神经痛40例,依据治疗用药不同将其分两组。对照组20例,用药选择卡马西平;实验组20例,用药选择加巴喷丁。观察两组疗效,比较分析。结果两组比较,实验组VAS改善明显(P <0.05),治疗有效率明显较高(P <0.05),不良反应较少(P <0.05),差异显著。结论加巴喷丁对三叉神经痛疗效确切,优于卡马西平,可推广。%Objective Clinical effects of gabapentin and carbamazepine in treatment of trigeminal neuralgia are to be comparatively studied.MethodsChoose 40 patients of trigeminal neuralgia who are treated in hospital from January 2014 to January 2015 and separate them into two groups according to different medication treatments; 20 patients in control group are given carbamazepine medication treatment and 20 patients in study group are given gabapentin medication treatment; and then make a comparative study on treatment effects between two groups.Results Patients’ VAS are improved better in study group (P < 0.05), and treatment efficacy in study group is much higher than that in control group (P < 0.05); besides, side-effect incidence in study group is less (P < 0.05) there is a treatment differential between two groups.Conclusion Gabapentin medication is much more effective in treatment of trigeminal neuralgia than carbamazepine medication; thus, such a treatment is quite worthwhile to be promoted and applied widespread.

  13. Preparation and Quality Evaluation of Carbamazepine Orally Disintegrating Tablets%卡马西平口腔速崩片的制备及质量评价

    Institute of Scientific and Technical Information of China (English)

    卫晓晓; 焦海胜

    2011-01-01

    OBJECTIVE: To prepare Carbamazepine (CBZ) orally disintegrating tablets and to evaluate the quality standard of it.METHODS: The tablets were prepared by directly powder compression method using microcrystaline cellulose (MCC) and croscarmellose sodium (CCNa) as disintegrants.The preparation method was optimized by orthogonal test using amount of MCC,CCNa and lactose as factors and with disintegrating time as index.The content of main components was determined by UV spectrophotometry, and the properties of the tablets were evaluated using dissolution rate and stability as index.The dissolution rate of CBZ orally disintegrating tablets was compared with common tablet, and the stability of CBZ orally disintegrating tablets was compared with raw material.RESULTS: The optimal formula was as follows: MCC 75 mg, CCNa 9 mg, lactose 30 mg.The quality of prepared tablets was in line with the standard.The disintegration time was (21 ± 3) s and the accumulative dissolution rate was 81.46% within 2 min.The accumulative dissolution rate was 71.46% within 90 min.Compared with raw material, the absorption peak of prepared tablets changed slightly.CONCLUSION: The preparation technology of orally disintegrating tablets is simple, controllable in quality.It should be kept in drug and cold environment.%目的:制备卡马西平(CBZ)口腔速崩片并评价其质量.方法:选用CBZ为主药,微晶纤维素(MCC)、交联羧甲基纤维素钠(CCNa)为崩解剂,以直接粉末压片法制备片剂;以MCC、CCNa、乳糖用量为考察因素,崩解时间为考察指标设计正交试验筛选处方;采用紫外分光光度法测定制剂中主药的含量,同时以崩解时间、溶出度及稳定性等指标进行质量评价,并与普通片剂比较溶出度,与原料药比较稳定性.结果:优选处方为MCC 75mg、CCNa 9mg、乳糖30mg.所制制剂含量均匀度符合规定,崩解时间为(21±3)s.溶出迅速,2 min内累积溶出率达81.46%;普通片剂90 min

  14. Clinical analysis of carbamazepine combined with baclofen treating trigeminal neuralgia%卡马西平联合巴氯芬治疗三叉神经痛的临床分析

    Institute of Scientific and Technical Information of China (English)

    程福璋

    2015-01-01

    Objective To explore the clinical effect of carbamazepine combined with baclofen treating trigeminal neu-ralgia. Methods 82 patients with trigeminal neuralgia meeting clinical diagnostic criteria and received in our hospital from February 2013 to February 2015 were selected as study object.Patients were divided into control group and treat-ment group by random number table method,and each group was 41 cases.Patients in control group were treated simply with carbamazepine,while patients in treatment group were given carbamazepine combined with baclofen.Disappear time of trigeminal neuralgia symptom,the total time of medicine treatment plan implement,treatment effect and incidence rate of adverse reaction and so on in patients between two groups was compared respectively. Results The disappear time of trigeminal neuralgia symptom and the total time of medicine treatment plan implement in treatment group [(7.32±1.08) d and (10.75±1.68) d] was obviously shorter than that of control group [(10.68±2.15) d and (14.79±2.53) d] respectively (P<0.05).The total effective rate in treatment group (90.3%) was obviously higher than that of control group (68.3%) (P<0.05).The incidence rate of adverse reaction in treatment group (2.4%) obviously lower than that of control group (17.1%) (P<0.05). Conclusion The clinical effect is very obvious by using carbamazepine combined with baclofen treat-ing trigeminal neuralgia.%目的:探讨卡马西平联合巴氯芬治疗三叉神经痛的临床效果。方法选择2013年2月~2015年2月我院收治的符合临床诊断标准的三叉神经痛患者82例作为研究对象,采取随机数字表法将其分成对照组和治疗组,每组41例。对照组患者给予单纯卡马西平治疗;治疗组患者给予卡马西平联合巴氯芬治疗。比较两组患者的三叉神经痛症状消失时间和用药治疗计划实施总时间、治疗效果、不良反应发生率等。结果治疗组患者的三

  15. Anhydrate to hydrate solid-state transformations of carbamazepine and nitrofurantoin in biorelevant media studied in situ using time-resolved synchrotron X-ray diffraction

    DEFF Research Database (Denmark)

    Bøtker, Johan Peter; Rantanen, Jukka; Arnfast, Lærke

    2016-01-01

    with different biorelevant media, simulated fasted and fed state intestinal fluids containing bile salt and dioleoylphosphatidylcholine (DOPC) micelles, DOPC/sodium dodecyl sulfate (SDS) mixture, bile salt solution and water. Two anhydrate compounds (carbamazepine, CBZ and nitrofurantoin, NF) with different......Abstract Transformation of the solid-state form of a drug compound in the lumen of the gastrointestinal tract may alter the drug bioavailability and in extreme cases result in patient fatalities. The solution-mediated anhydrate-to-hydrate phase transformation was examined using an in vitro model...... analysis, PCA) and compared to those for nitrofurantoin (NF). The study showed that the solution-mediated phase transformation of CBZ anhydrate was remarkably faster in the DOPC/SDS medium compared to transformation in all the other aqueous dispersion media. The conversion time for CBZ anhydrate in water...

  16. Clinical efficacy and mechanism of flunarizine combined with carbamazePine in migraine%氟桂利嗪联合卡马西平治疗偏头痛的疗效及作用机制

    Institute of Scientific and Technical Information of China (English)

    刘英; 付勇; 黄泗霖

    2015-01-01

    Objective It is to approach the clinical efficacy and mechanism of flunarizine combined with carbamazepine in migraine. Methods 156 patients with migraine were divided into 2 groups,78 cases in each group. The patients in control group were treated with flunarizine,while the observation group was given carbamazepine. The courses of treatment in both groups were three months. The differences of HAMA,HAMD,BRMS,headache degree,seizure frequency,duration time, accompanying symptoms,adverse reaction,mean flow velocity of intracranial vessel,ET,NO,5 -HT and β-EP before and after treatment were observed in two groups. Results The HAMA,HAMD,BRMS,headache degree,seizure frequency and duration time after treatment were obviously improved than before treatment in both groups(all P0. 05). The mean flow ve-locity of intracranial vessel in both groups after treatment was obviously slower than before treatment(P0.05)。治疗后2组颅内动脉血流速度均较治疗前显著减慢(P<0.05或 P<0.01),且观察组显著慢于对照组(P <0.05或 P <0.01)。治疗后2组血浆NO、5-HT和β-EP水平均较治疗前显著上升(P均<0.01),ET 水平均显著下降(P 均<0.01),而观察组各指标改善情况均优于对照组(P均<0.05)。结论氟桂利嗪联合卡马西平可显著改善偏头痛患者焦虑、抑郁和狂躁等不良情绪,缓解头痛程度,降低发作频率,缩短发作时间,调节血管、神经和神经递质的功能,在改善不良情绪的同时,有效缓解偏头痛病情,形成良性循环。

  17. Observation of curative effect by carbamazepine in the treatment of pediatric refractory generalized convulsive status epilepticus%卡马西平治疗小儿难治性惊厥持续状态疗效观察

    Institute of Scientific and Technical Information of China (English)

    唐容华; 周江堡

    2016-01-01

    ObjectiveTo investigate effective treatment method for pediatric refractory generalized convulsive status epilepticus.MethodsA total of 14 children patients with refractory generalized convulsive status epilepticus received carbamazepine after failed conventional first and second line drug, and their curative effects were observed.ResultsAmong 14 cases, there were 6 cases with obviously reduced convulsions times after 24 h of medication and controlled convulsions after 48 h, 6 cases with obviously reduced convulsions times after 48 h of medication and controlled convulsions after 72 h, and the other 2 cases with obviously reduced convulsions times after 72 h, along with 1 quit case of them due to severe raticide poisoning. There was no case with adverse drug reaction.ConclusionCarbamazepine provides remarkable effect for pediatric refractory generalized convulsive status epilepticus, especially for refractory partial convulsive status epilepticus. Course of treatment requires further investigation.%目的:探讨小儿难治性惊厥持续状态的有效治疗方法。方法14例难治性惊厥持续状态患儿,在使用常规一线、二线止惊药物失败后,开始采用卡马西平治疗,观察疗效。结果14例患儿中,6例患儿在给药24 h后惊厥次数明显减少,48 h惊厥控制;6例患儿在给药48 h后惊厥次数明显减少,72 h惊厥控制;另2例患儿在给药72 h后惊厥次数明显减少,其中1例灭鼠药中毒后终因病情太重放弃治疗,自动出院。无一例出现药物不良反应。结论卡马西平对小儿难治性惊厥持续状态有明显疗效,尤其对难治性部分性惊厥持续状态效果好,其使用疗程有待进一步探索。

  18. 卡马西平与加巴喷丁对复发性三叉神经痛的治疗价值比较%Therapeutic Value Comparison of Carbamazepine and Gabapentin in Recurrent Trigeminal Neuralgia

    Institute of Scientific and Technical Information of China (English)

    张雪

    2015-01-01

    目的:比较卡马西平与加巴喷丁治疗复发性三叉神经痛的临床应用价值。方法选取2014年1月~2015年1月我院收治的复发性三叉神经痛患者56例,将其随机分为对照组与观察组,对照组给予卡马西平治疗,观察组给予加巴喷丁治疗。结果两组患者总有效率比较无差异(P>0.05);治疗后两组VAS疼痛评分均低于治疗前,且观察组不良反应发生率低于对照组,有统计学意义(P0.05),after treatment VAS pain scores were lower than before treatment,and observed the adverse reaction rate group were less than the control group,with statistical significance(P<0.05). Conclusion Carbamazepine and gabapentin in treatment of recurrent trigeminal neuralgia with good results,but gabapentin and more secure.

  19. Effects of reproductive system in experimental male rats with carbamazepine%卡马西平对健康及癫雄性大鼠生殖系统相关指标的影响

    Institute of Scientific and Technical Information of China (English)

    刘绪宏; 张辉; 谭梅; 许笑天; 伍春华

    2014-01-01

    concentration carbamazepine infused into stomach .Blood, testis and epididymis, and sperms were sampled; serum sex hormones , viscera coefficient , sperm counts , sperm motility and morphology were observed for analyzing on effects male epileptrc rats’ reproductive system .Results In the epilepsy model rats receiving high , medium and low concentration CBZ showed that LH , FSH, E2 were significantly higher than in controls , there were but no significant differences between the three concentration groups . Progesterone ( P) levels of three concentrations were obviously lower than in controls , but in low concentration group was significantly lower than in the other two concentration groups .Testosterone ( T) levels in three concentration groups were significantly lower than in healthy group.No changes were found in PRL .In the health control Wistar rats receiving .high, medium and low concentration CBZ , LH and FSH were significantly higher than in controls , testosterone ( T) levels in three concentration groups were significantly lower than in health group , especially the high concentration group ,PRL levels in medium and low concentration group obviously lower than in controls.There was no difference in P and E 2.There were no changes in weight and testicular weight and testicular viscera coeffi -cient between male epilepsy rats and health group , but epididymis weight and epididymis viscera coefficient were obviously lower in the health rats with three concentration CBZ than in controls .No sperm count change in the three concentrations for male epilepsy rats and health group , but both of them had the lower sperm activity rate than in controls , especially in high concentration group .Conclusions Carbamazepine itself for male rats reproductive system has obvious side effects and obvious drug concentration relevance , both car-bamazepine and epilepsy also present the part of the side effects of correlation concentration ,but the mechanism is relatively complex , caused

  20. 加巴喷丁、卡马西平治疗复发性三叉神经痛的疗效对比观察%A comparative study on the efficacy of gabap-entin and carbamazepine in the treatment of recurrent trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    杨艳丽

    2015-01-01

    AIM: To compare and observe the clinical efficacy of gabapentin and carbamazepine in the treatment of recurrent trigeminal neuralgia. METHODS: A total of 76 patients with recurrence of trigeminal neuralgia in our hospital were selected and randomly divided into carbamazepine group and gabapentin group. Patients in carbamazepine group were treated by carbamaz⁃epine, and those in gabapentin group were treated by gabapentin. Clinical curative effect was compared between the two groups. RESULTS: Dosage of carbamazepine was less than that of gabapentin, and the difference was statistically significant ( P<0.05) . VAS of 1, 2 and 4 weeks after treatment in the two groups were significantly higher than that before treatment, and the difference was statistically significant ( P<0. 05 ) . LSI⁃B of the gabapentin group after 4⁃week treatment was higher than that of the carbamazepine group, and LSI⁃B improved in both groups after treatment, with statistically significant difference ( P<0.05) . Besides, incidence of adverse reactions of gabapentin group was lower than that of the gabapentin group, and the difference was statistically significant (P<0.05). CONCLUSION: The clinical curative effect of carbamazepine and gabapentin in the treatment of recurrent trigeminal neuralgia are almost the same, but gabapentin cause lower incidence of adverse reactions, improves the quality of life of patients more obviously, and is a better choice for the treatment of trigeminal neuralgia.%目的:观察加巴喷丁与卡马西平治疗复发性三叉神经痛的临床疗效.方法:选取我院收诊的复发性三叉神经痛患者76例,采取数字随机法分成加巴喷丁组和卡马西平组,加巴喷丁组采取加巴喷丁治疗,卡马西平组采取卡马西平治疗,比较两组临床疗效.结果:卡马西平组药物用量低于加巴喷丁组,差异有统计学意义(P<0.05).两组治疗后1、2、4周VAS评分均高于治疗前,差异有

  1. Effects of carbamazepine and left levetiracetam on cognitive function of children with benign epilepsy combined with centrotemporal spike waves%卡马西平、左乙拉西坦对伴中央-颞区棘波的良性癫痫患儿认知功能的影响

    Institute of Scientific and Technical Information of China (English)

    顾红菲; 宁宪嘉

    2012-01-01

    Objective: To compare the effects of carbamazepine and left levetiracetam on cognitive function of children with benign epilepsy combined with centrotemporal spike waves. Methods: Eighty children who were diagnosed as benign epilepsy combined with centrotemporal spike waves definitely were selected and randomly divided into carbamazepine group and left levetiracetam group, all the children were treated for six months. The electroencephalogram ( EEG), latent period of P3, and the changes of cognitive function of the children were compared between the two groups. Results: The epileptiform discharges after treatment in left levetiracetam group were significantly less than those in carbamazepine group, the latent period of P3 in left levetiracelam group shortened significantly (P 0.05) . Verbal intelligence quotient and performance intelligence quotient of the children in left levetiracetam group were significantly higher than those in carbamazepine group (P < 0.05) . Conclusion ? Left levetiracetam can improve the cognitive function of children with benign epilepsy combined with centrotemporal spike waves.%目的:比较卡马西平、左乙拉西坦对伴中央-颞区棘波的良性癫痫患儿认知功能的影响.方法:选择诊断明确的伴中央-颢区棘波的良性癫痫患儿80例随机分为卡马西平和左乙拉西坦组,均治疗6个月.比较两组患儿治疗前后脑电图、P3潜伏期及认知功能的变化.结果:左乙拉西坦治疗组治疗后临床下痫样放电较卡马西平组减少,P3潜伏期缩短(均P<0.05).治疗前后两组总智商(FIQ)差异无统计学意义(P>0.05).左乙拉西坦治疗组儿童语言智商(VIQ)、操作智商(PIQ)较卡马西平组提高(P<0.05).结论:左乙拉西坦对伴中央-颞区棘波的小儿良性癫痫患儿的认知功能有改善作用.

  2. 加巴喷丁与卡马西平治疗原发性三叉神经痛对照研究%Comparison and research on the clinical effects of Gabapentin and Carbamazepine in the treatment primary trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    周梨

    2014-01-01

    目的:观察加巴喷丁与卡马西平治疗原发性三叉神经痛的临床效果并进行对比。方法随机选取我院原发性三叉神经痛患者86例,随机分为2组。实验组接受加巴喷丁治疗,对照组接受卡马西平治疗,治疗前后采用视觉模拟评分法(VAS)评分。观察2组患者满意度、康复情况以及不良反应。结果实验组有效37例(86.05%)对照组有效34例(79.07%);2组VAS评分均下降,但差异无统计学意义(P>0.05);患者满意度和不良反应比较差异均有统计学意义(P<0.05)。结论加巴喷丁与卡马西平治疗原发性三叉神经痛均有较好疗效,但加巴喷丁不良发应少于卡马西平。%Objective To observe the clinical effects of Gabapentin and Carbamazepine in the treatment of primary trigem-inal neuralgia patients.Methods Eighty-six cases of primary trigeminal neuralgia patients in our hospital randomly were select-ed and divided into two groups averagely.Patients in experimental group received Gabapentin ,while patients in control group received Carbamazepine.The visual analogue scale (VAS) was used to evaluate the feelings and investigate the degree of satis-faction ,recovery situations and adverse reactions. Results There were 37 cases with effective efficacy in experimental group , it was 86.05%.There were 34 cases with effective efficacy in control group ,it was 79.07%.The value of VAS decreased in the two groups and the discrepancy was not clear.The degree of satisfaction and adverse reactions were different obviously in the two groups. Conclusion Both Gabapentin and Carbamazepine have good curative effect for primary trigeminal neuralgia pa-tients.However ,Gabapentin performs better in the degree of satisfaction and adverse reactions than Carbamazepine.

  3. Effects of carbamazepine on maternal and neonatal outcomes of pregnant women with epilepsy and the intervention effect of folic acid%卡马西平对妊娠合并癫痫患者母婴结局的影响及叶酸的干预效果分析

    Institute of Scientific and Technical Information of China (English)

    吴静; 李云霞; 郑丽娜

    2016-01-01

    ObjectiveTo investigate the effect of carbamazepine on maternal and neonatal outcomes of pregnant women with epilepsy and the intervention effect of folic acid.MethodA total of 56 pregnant women with epilepsy who received treatment in our hospital from May 2011 to June 2014 were selected and randomly divided into control group and observation group, 28 cases in each group. Control group patients were treated with carbamazepine, while observation group patients received folic acid treatment on the base of routine therapy. Observed and compared the epileptic seizures, clinical complications and the maternal and neonatal outcomes between the two groups.ResultThe incident of epileptic seizure, hypertension syndrome of pregnancy and stnatal depression of observation group was less than control group (P0.05). The incident of neonatal malformations, and low body weight of observation group was less than control group (P0.05).ConclusionCarbamazepine can control the seizure frequency of epilepsy in pregnancy women, and the combined therapy of carbamazepine and folic acid can reduce the fetal malformation rate.%目的:探讨卡马西平对妊娠合并癫痫患者母婴结局的影响及叶酸的干预效果。方法选取2006年5月至2015年6月于本院就诊的妊娠合并癫痫患者56例为研究对象,采用随机数表法将其分为对照组和观察组,每组各28例。对照组患者给予卡马西平,观察组患者在对照组治疗基础上联合服用叶酸。观察两组患者癫痫发作程度、妊娠期并发症发生情况及母婴结局。结果观察组患者癫痫发作频率明显少于对照组(P<0.05);观察组患者妊娠高血压综合征、妊娠期抑郁发生率及围生期癫痫发作次数较对照组明显减少(P<0.05);而两组患者自然流产、前置胎盘、早产发生率比较均无明显差异(P>0.05)。观察组新生儿畸形、低体重儿发生率较对照组明显升高(P<0.05),两组胎

  4. 128例口服卡马西平导致不良反应文献分析%Literature Analysis of 128 Cases With Carbamazepine Induced Adverse Reactions

    Institute of Scientific and Technical Information of China (English)

    李燕; 赵生芳; 段金菊; 王芳

    2012-01-01

    Objective To explore the general characteristics of adverse drug reactions (ADR) caused by the carbamazepine (CMP), and provide some information for clinical medication . Methods The related reports about ADR caused by CMP were searched and retrospective analyzed in medical and academic journals from China Journal Full-Text Database between January 2000 and October 2009 . At last, a total of 128 cases were include into this study . The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Shanxi Medical University . Results Clinical manifestations of ADR caused by the CMP were complex and diverse . The top three incident rate of systemic injury were skin and its appendages injury (58 .60% , 75/128) , central and peripheral nervous system injury (14 .84% , 19/128) and blood disorders (10.16% , 13/128). There had significant difference of incident rate between males and females (P<0 .05) . The ADR can occur in any age stages , and patients older than 60-year-old had the highest incident rate (11 .72% , 5/128). The ADR caused by drug combination may have serious results , such as bullous epidermal necrolysis drug eruption , generalized myoclonic seizures and leukocyte reduction . In 128 patients , the cure rate was 93 .75% (120/128), occurrence rate of sequelae was 0 .78% (1/128) and rate of rescue invalid death was 5 .47% (7/128) . Conclusions Clinicians should pay attention to the ADR caused by CMP, especially guard against the occurrence of serious drug-induced rash , aplastic anemia and acute renal failure. And further knowledge about serious ADR, such as bullous epidermal necrolysis drug eruption, generalized myoclonic seizures and leukocyte reduction caused by drug combination , should be attention .%目的 探讨卡马西平(CMP)导致不良反应(ADR)的一般规律及特点,为临床合理用药提供参考.方法 采用回顾性分析方法,选择2000年1月至2009年10月中国期刊全文数据库收载的国

  5. 卡马西平对癫痫患者血同型半胱氨酸、叶酸、维生素B12水平的影响%Effect of carbamazepine on the levels of homocysteine, folic acid, vitamin B12 in patients with epilepsy

    Institute of Scientific and Technical Information of China (English)

    张其梅; 夏杰; 张建宇

    2013-01-01

    Objective To investigate the effect of carbamazepine (CBZ) on the levels of homocysteine (Hey), folic acid, vitamin B12 (VitB12). Methods The levels of blood Hey, folic acid, VitBu were measured in epilepsy patients treated by CBZ (CBZ group), epilepsy patients not treated by CBZ (the epilepsy control group), healthy individuals (the normal control group). The results were compared between the three groups. Results The blood Hey levels in CBZ group were significantly higher than those in the epilepsy control group and the normal control group (P<0.01), while the levels of folic acid were significantly lower (P<0.05). The levels of VitB12 exhibited a downward trend in CBZ group, but showed no statistically significant difference with the other two groups. Conclusion CBZ can elevate the levels of Hey and reduce the level of folic acid in patients with epilepsy. Epilepsy patients taking CBZ for a long time should be monitored for the levels of blood Hey, folic acid, VitB12, and timely supplemented with folic acid and B vitamins in order to prevent the occurrence of thromboembolic events.%目的 探讨卡马西平(Carbamazepine,CBZ)对血同型半胱氨酸(Homocysteine,Hcy)、叶酸、维生素B12(vitaminB12,VitB12)水平的影响.方法 分别检测CBZ单药治疗癫痫患者(CBZ组)的血Hcy、叶酸、VitB12水平,并与未服用抗癫痫药的患者(癫痫对照组)及健康对照组进行比较.结果 CBZ组患者血Hcy水平明显高于癫痫对照组和正常对照组(P<0.01),叶酸水平低于癫痫对照组和正常对照组(P<0.05),VitB12水平有下降趋势,但与两对照组比较,差异无统计学意义(P>0.05).结论 CBZ可引起癫痫患者血Hcy水平升高和叶酸水平降低;长期服用CBZ的癫痫患者应监测血Hcy、叶酸、VitB12浓度,及时补充叶酸和B族维生素,以预防血栓事件的发生.

  6. Comparison of the efficacy of carbamazepine, haloperidol and valproic acid in the treatment of children with Sydenham´s chorea: clinical follow-up of 18 patients Comparación de la eficacia de carbamazepina, haloperidol y acido valproico en el tratamiento de niños con corea de Sydenham: seguimiento clínico de 18 pacientes

    Directory of Open Access Journals (Sweden)

    Joaquín Peña

    2002-06-01

    Full Text Available In order to compare and contrast the efficacy of haloperidol, carbamazepine, and valproic acid in the treatment of Sydenham´s chorea a prospective study including 18 cases of this disorder was undertaken. Age of patients ranged from 7 to 15 years. Ten children were female and 8 were male. All but one had generalized, either symmetric or asymmetric chorea. The patients were divided in three equal groups, and were given a standardized dose of each of the drugs built-up over a week. Following therapy, the six children receiving valproic acid showed remarkable improvement, without side effects. Five patients receiving carbamazepine showed improvement without side effects. Only three of the patients that received haloperidol improved. In the 4 cases that did not show clinical improvement after one week of treatment, therapy with valproic acid led to disappearance of the symptoms in a lapse that ranged from 4 to 7 days. Recurrence related to discontinuation of treatment was observed in two patients. In view of the present results we recommend valproic acid as the first choice drug to treat Sydenham chorea.A fin de comparar y contrastar la eficacia de haloperidol, carbamazepina y ácido valproico en el tratamiento de la corea de Sydenham, se realizó un estudio prospectivo que incluyó 18 casos de esta patología. La edad de los pacientes varió de 7 a 15 años. Diez de los niños eran varones y el resto hembras. A excepción de uno de ellos, todos tenían corea generalizada, simétrica ó asimétrica. Los pacientes fueron divididos en tres grupos iguales, a cada uno de los cuales se le administró una dosis estandarizada de los medicamentos mencionados durante una semana. Luego del tratamiento, los seis pacientes que recibieron ácido valproico mostraron mejoría notable sin efectos colaterales. Cinco de los seis pacientes que recibieron carbamazepina exhibieron mejoría sin efectos colaterales. Solo tres de los pacientes que recibieron haloperidol

  7. Pain relief clinical effect of carbamazepine combined nursing intervention on patients with primary trigeminal neuralgia%卡马西平联合护理干预对缓解原发性三叉神经痛患者疼痛的临床效果

    Institute of Scientific and Technical Information of China (English)

    杜玉娟

    2015-01-01

    Objective:To observe the clinical effect pain relief with carbamazepine combined nursing intervention on patients with primary trigeminal neuralgia.Method:76 cases of patients with primary trigeminal neuralgia from February 2012 to October 2014 were randomly divided into the control group and the observation group,with 38 cases in each group.The control group were given carbamazepine treatment orally,the starting quantity was 0.1 g/time,3 times/d,gradually increasing doses to 0.4~0.6 g according to the situation of the pain,and gradually reduced after the pain controlled.The observation group were treated with targeted nursing intervention on the basis of the treatment above,including daily life care,medication nursing,psychological counseling,pain nursing,continuous treatment for 30 days.The patients' pain,changes of the SAS scores and SDS scores of the two groups were observed and the clinical treatment effective rate were compared.Results:The pain of the two groups were alleviated after treatment,VAS scores were reduced,that of the observation group were lower than that of the control group,the differences were statistically significant(P<0.05).The anxiety,depression and other negative emotions of the two groups after treatment were improved,the SAS scores and SDS scores were significantly decreased,that of the observation group were lower than that of the control group,the differences were statistically significant(P<0.05).The effective rate of the observation group 92.1% was obviously higher than that of the control effectiveness 73.6% ,the difference was statistically significant(P<0.05).Conclusion:Carbamazepine combined nursing intervention could reduce the pain symptoms of patients with primary trigeminal neuralgia effectively and improve the patient's negative emotions and improve the treatment enthusiasm and confidence in clinical,worthy of clinical promotion.%目的:观察用卡马西平联合护理干预对缓解原发性三叉神经痛患者疼

  8. Efeitos neuromusculares in vitro e in vivo do atracúrio e do rocurônio em ratos submetidos a tratamento de sete dias com carbamazepina Efectos neuromusculares in vitro e in vivo del atracurio y del rocuronio en ratones sometidos a tratamiento de siete días con carbamazepina In vitro and in vivo neuromuscular effects of atracurium and rocuronium in rats treated with carbamazepine for seven days

    Directory of Open Access Journals (Sweden)

    Caroline Coutinho de Barcelos

    2008-04-01

    neuromuscular producido por el rocuronio y atracurio en ratones tratados con carbamazepina y determinó las concentraciones de citocromo P450 y b5 reductasis en microsomas hepáticos. MÉTODO: Ratones fueron tratados por siete días con carbamazepina (CBZ - 40 mg.kg-1 a través de una sonda y sacrificados al octavo día bajo anestesia con uretana. Las preparaciones in vitro e in vivo fueron montadas de acuerdo con las técnicas de Bulbring y de Leeuwin y Wolters, respectivamente. Las concentraciones y dosis utilizadas de los bloqueadores en las preparaciones in vitro e in vivo fueron, respectivamente, 20 µg.mL-1 y 0,5 mg.kg-1 para atracurio (ATC; 4 µg.mL-1 y 0,6 mg.kg-1 para rocuronio (ROC. Cada protocolo tuvo un n = 5 y las respuestas fueron observadas por 60 minutos. Los efectos del ATC y ROC fueron evaluados en las preparaciones de ratones tratados (Cbz t y comparados a los observados en los de ratones no tratados (CBZst. Las concentraciones de citocromo P450 y b5 reductasis fueron determinadas en microsomas aislados de hígados de ratones tratados (CBZt y comparadas con las obtenidas en ratones no tratados (CBZst RESULTADOS: La carbamazepina no alteró la amplitud de las respuestas musculares; in vitro y in vivo, no hubo diferencia entre el bloqueo neuromuscular producido por el atracurio en las preparaciones CBZt versus CBZst; el bloqueo neuromuscular producido por el Rocuronio en las preparaciones CBZt fue potenciado in vitro. La carbamazepina no alteró las concentraciones de citocromo P450 y b5. CONCLUSIONES: El tratamiento por siete días con carbamazepina, no influenció en el bloqueo producido por el atracurio, y alteró in vitro los efectos del rocuronio. El tiempo de tratamiento no fue suficiente para causar la inducción enzimática y disminuir la sensibilidad al rocuronio.BACKGROUND AND OBJECTIVES: This experimental study investigated the in vitro and in vivo neuromuscular blockade of rocuronium and atracurium in rats treated with carbamazepine and determined

  9. 卡马西平诱导儿童伴中央颞区棘波的良性癫癎出现癫癎性电持续状态的初步研究%The correlation of carbamazepine with occurrence of electrical status epilepticus during sleep in benign epilepsy with centrotemporal spikes

    Institute of Scientific and Technical Information of China (English)

    黄启坤; 华青

    2015-01-01

    目的:探讨卡马西平(CBZ)诱导儿童伴中央中颞区棘波的良性癫癎(BECT )发生睡眠期癫癎性电持续状态(ESES)的相关因素。方法:回顾分析219例BECT治疗过程中6例出现ESES的病历资料。结果:CBZ治疗组123例中有6例出现ESES ,非CBZ治疗组96例中无ESES发生,两组发生率比较差异有统计学意义。6例ESES中,有5例出现于Rolandio区棘波组,1例出现于非棘波组,两组发生率比较差异有统计学意义。结论:CBZ能导致BECT 出现ESES现象,Rolando区棘波与 ESES的发生有一定相关性。%Objective:To explore the correlation of carbamazepine (CBZ) with occurrence of electri‐cal status epilepticus during sleep ( ESES) in benign epilepsy with centrotemporal spikes (BECT) .Meth‐ods:The clinical data of 6 patients with ESES out of 219 patients with BECT in our hospital were analyzed retrospectively .Results:The onset age of 219 children ranged from 4 years to 12 years .6 cases wilh ESES were found in 123 patients with CBZ(CBZ group) .No patient who was treated with valproate or topira‐mate showed ESES in 96 patients(non‐CBZ group) .There was a significant difference between CBZ group and non‐CBZ group(P<0 .05) .The duration of ESES disappearence in EEG examination ranged between 3 and 6 months after discontinuation of CBZ ..Five cases in 6 patients with ESES suffered from centro‐temporal spikes .Conclusion:CBZ can induce ESES in the treatment of BECT ,although it rarely happens . There is a certain correlation between ESES and BECT with spike waves in rolandic area .

  10. Restricted-access media high pressure liquid chromatography vs fluorescence polarization immunoassay for analysis of carbamazepine in human plasma%浸透限制固定相高压液相色谱法和荧光偏振免疫法测定人血中卡马西平浓度的比较

    Institute of Scientific and Technical Information of China (English)

    马骏; 朱彭龄; 谢景文; 贾正平; 杨金升

    2002-01-01

    目的:比较浸透限制固定相高效液相色谱法(RAM-HPLC)与荧光偏振免疫法(FPIA)测定人血中的卡马西平(CBZ)浓度.方法:建立一种直接进样RAM-HPLC法测定病人静脉和指端血浆的CBZ浓度.结果:两种测定方法都不需样品前处理,有好的重现性和近100%的回收率.FPIA测定静脉血样CBZ的结果与RAM-HPLC分别测定静脉和指端血样CBZ的结果有良好的相关性(R=0.989,0.995),但相差显著(P<0.05);而RAM-HPIC法测定静脉和指端血样两组数据间相差不显著(P>0.05).结论:RAM-HPLC和FPIA法均可测定CBZ浓度.在治疗药物监测中,FPIA更适合常规的监测;RAM-HPLC法更适用于相关研究和特殊病例监测,这里我们成功地应用于测定人外周微量血样中CBZ的浓度.%AIM: To compare restricted-access media high performance liquid chromatographic ( RAM-HPLC )method with fluorescence polarization immunoassay (FPIA) for analysis of carbamazepine (CBZ) in human blood. METHODS: An RAM-HPLC method was established for the determination of CBZ in plasma.RESULTS: The two methods do not need sample cleanup prior to analysis and they have almost 100 % recovery and good reprodtucibility. There is a good correlation between the CBZ concentration in venous plasma samples determined by FPIA and that in both venous and fingertip plasma samples obtained by RAM-HPLC, the correlation coefficients being 0.989 and 0.995, respectively. It is shown by t-test that the data sets of venous and fingertip plasma samples given by RAM-HPLC are consistent with each other but significantly different from the results obtained by FPIA. CONCLUSION: Both direct injection RAM-HPLC and FPIA may be applied in determining CBZ in therapeutic drug monitoring (TDM).FPIA is well-suited to the routine TDM. RAM-HPLC is more useful in TDM related research and especial cases.

  11. Skin reaction to carbamazepine or DRESS syndrome: a case presentation

    Directory of Open Access Journals (Sweden)

    Emigdio Jesús Cabrera Fundora

    2016-03-01

    Full Text Available La carbamazepina es un medicamento de empleo habitual que puede producir efectos secundarios y en algunos casos reacciones adversas como vértigos, somnolencia y reacciones cutáneas que pueden ser severas como el síndrome DRESS (Drug Rash with Eosinophilia and Systemic Symptoms. Se caracteriza por erupción cutánea tardía y lenta progresión, linfocitos atípicos con eosinofilia y síntomas sistémicos como fiebre, adenopatías, hepatopatía y trastornos renales, pudiendo llegar a la muerte del paciente. Se presenta un caso para destacar la importancia del diagnóstico temprano del síndrome DRESS, que garantice un manejo adecuado para la supervivencia del paciente. Es una paciente bajo tratamiento con carbamazepina para neuralgia del trigémino, que al tiempo comienza con lesiones cutáneas que se interpretan como reacción de hipersensibilidad. Al no mejorar con tratamiento inicial y empeorar el cuadro cutáneo, acompañándose de síntomas generales, se realizan análisis complementarios y se plantea el diagnóstico de síndrome DRESS que se resuelve definitivamente con esteroides.

  12. Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine

    Directory of Open Access Journals (Sweden)

    Nair Rahul

    2012-06-01

    Full Text Available Abstract The present work aims at preparing aqueous suspension of Solid lipid Nanoparticles containing Chitosan (CT which is a biopolymer that exhibits a number of interesting properties which include controlled drug delivery. Carbamezapine (CBZ is a lipophilic drug which shows it antiepileptic activity by inactivating sodium channels. The solid lipid Nanoparticles (SLN of Chitosan-CBZ were prepared by using solvent injection method using ethanol as organic solvent. The prepared SLN formulations exhibited high encapsulation efficiency, high physical stability. The drug incorporated SLNs have demonstrated that the controlled release patterns of the drug for prolonged period. The prepared SLNs were characterized for surface morphology by SEM analysis, entrapment efficiency, zeta potential, FTIR, DSC and In-vitro diffusion studies. The hydrodynamic mean diameter and zeta potential were 168.7 ±1.8 nm and −28.9 ±2.0 mV for SLN-chitosan-CBZ respectively. Therefore chitosan-SLN can be good candidates to encapsulate CBZ and to increase its therapeutic efficacy in the treatment of Epilepsy.

  13. [Clinical improvement of diabetic neuropathy with carbamazepine or diclofenac treatment].

    Science.gov (United States)

    Tinoco-Samos, Andrea; Córdova-Pérez, Nydia; Arenas-Téllez, Juan Manuel; Vargas-Girón, Antonio; Zárate, Arturo; Hernández-Valencia, Marcelino

    2013-01-01

    Introducción: la neuropatía diabética afecta diversos aspectos de la vida del paciente, pero aún no hay un tratamiento específico. Se hizo un análisis comparativo de la mejoría clínica con manejo de carbamazepina y diclofenaco. Métodos: estudio prospectivo, longitudinal, de dos grupos de pacientes diabéticos con signos y síntomas de neuropatía diabética: 30 usaron 200 mg de carbamazepina cada 24 horas por una semana, con incremento gradual hasta 200 mg cada seis horas por 10 meses; 29 utilizaron 100 mg de diclofenaco sódico cada 12 horas. Se hicieron evaluaciones bimestrales para graduar el dolor según la percepción del paciente. Los estudios de laboratorio incluyeron glucosa y perfil de lípidos. Se empleó Anova para mediciones repetidas. Resultados: los pacientes tratados con carbamazepina no tuvieron dolor después de 10 meses de tratamiento, a diferencia del grupo con diclofenaco (p fuerza muscular, la presencia de pulsos y la percepción de temperatura y presión (p < 0.05). Los tres últimos se deterioraron con el diclofenaco. Conclusiones: hay que reconocer la sintomatología en pacientes diabéticos para dar el tratamiento adecuado.

  14. Reação cutânea grave induzida por carbamazepina no tratamento da neuralgia pós-herpética: relato de caso Reacción cutánea grave inducida por la carbamazepina en el tratamiento de la neuralgia postherpética: relato de caso Severe carbamazepine-induced cutaneous reaction in the treatment of post-herpetic neuralgia: case report

    Directory of Open Access Journals (Sweden)

    João Batista Santos Garcia

    2010-08-01

    . CONCLUSIONES: La SSJ/NET es una reacción cutánea grave con potencial para la morbilidade y mortalidad elevadas y que exige una intervención rápida y un manejo adecuado. También alertamos sobre el uso de la carbamazepina, que debe siempre ser inspeccionado, especialmente en los ancianos.BACKGROUND AND OBJECTIVES: Post-herpetic neuralgia (PHN is the main complication of herpes zoster. Carbamazepine (CBZ, a well-tolerated anticonvulsant, but frequently associated with severe cutaneous reactions, such as the Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN is used in the treatment of this complication. The objective of this article was to report a case of SJS/TEN secondary to CBZ in a patient with PHN. CASE REPORT: This is a female patient with continuous severe, burning, chock-like pain in the thoracic region and dorsum associated with reduced strength in the ipsilateral upper limb and diaphoresis. She had crusty and erythematous lesions in the dorsal region of the thorax with allodynia and dysesthesia in the affected dermatome. She was treated with CBZ 300 mg.day-1, amitriptyline (AMT 12.5 mg at bedtime, and infiltration with local anesthetic in the affected region. After 15 days, she developed malaise, fever, muscle pain, and arthralgia with a mild non-specific cutaneous rash. Carbamazepine was discontinued immediately. One week later, she was hospitalized with urticaria, generalized exanthema, erythematous cutaneous eruptions, bullae, and purpuric maculae all over her body. The impression was of carbamazepine-induced SJS/TEN. She evolved with progressive worsening of her symptoms, with increase in the number and size of cutaneous lesions, besides generalized erythematous macular rash, areas of necrosis, and erosions with symmetrical loosening of the epidermis in face, neck, thorax, dorsum, and limbs, affecting more that 50% of her body surface, besides involvement of buccal, conjunctival, and genital mucosa with vesicular erosions. She had progressive

  15. Quantitative bioanalytical and analytical method development of dibenzazepine derivative, carbamazepine: A review

    OpenAIRE

    Prasanna A. Datar

    2015-01-01

    Bioanalytical methods are widely used for quantitative estimation of drugs and their metabolites in physiological matrices. These methods could be applied to studies in areas of human clinical pharmacology and toxicology. The major bioanalytical services are method development, method validation and sample analysis (method application). Various methods such as GC, LC–MS/MS, HPLC, HPTLC, micellar electrokinetic chromatography, and UFLC have been used in laboratories for the qualitative and qua...

  16. [A proposal for a model to replace carbamazepine or oxcarbazepine by eslicarbazepine acetate in clinical practice].

    Science.gov (United States)

    Poza-Aldea, J J

    2016-09-01

    Introduccion. Durante muchos a˜os, la carbamacepina (CBZ) ha sido el farmaco de referencia para el tratamiento de las crisis epilepticas parciales. Sin embargo, los problemas asociados de su farmacocinetica y tolerabilidad han llevado al desarrollo de otros derivados, como la oxcarbacepina (OXC) y, mas recientemente, el acetato de eslicarbacepina (ESL), que obvien estos inconvenientes. Desarrollo. En la practica clinica, se presenta con relativa frecuencia la posibilidad de sustituir la CBZ o la OXC por ESL, buscando mantener la eficacia de los predecesores y ganar las ventajas en el ambito de farmacocinetica y tolerabilidad que ofrece este ultimo derivado. Para ello es indispensable disponer de una equivalencia aproximada de dosis y un protocolo de intercambio. La presente revision ofrece un modelo practico y razonado para realizar el cambio. Conclusiones. El paso de OXC a ESL se puede realizar de un dia para otro con una equivalencia de dosis de 1-1,5 a 1. La sustitucion de CBZ por ESL debe ser mas progresiva, y la equivalencia de dosis se establece en 1-1,3 a 1.

  17. Is there an association between maternal carbamazepine use during pregnancy and eye malformations in the child?

    NARCIS (Netherlands)

    Kroes, HY; Reefhuis, J; Cornel, MC

    2002-01-01

    Purpose: To check for an association between carbamazepme (CBZ) use by the mother during pregnancy and congenital eye malformations (i.e., anophthalmia, microphthalmia, and coloboma) in the child, as suggested by Sutcliffe et al. (1998), who reported four cases. Methods: We checked all the cases wit

  18. Progress in research on the carbamazepine dosage forms%卡马西平制剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈宝; 郑思嘉; 吴传斌

    2008-01-01

    通过查阅大量的文献,对近年来卡马西平在制剂方面的研究进展进行整理分析,阐述卡马西平制剂在各种给药途径特别是口服给药的新进展,提出今后的研究方向重点是提高卡马西平口服制剂的生物利用度和改善口服制剂的稳定性.

  19. Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; Pennings, Jeroen L. A.; Piersma, Aldert H.

    2015-01-01

    Differentiating pluripotent stem cells in vitro have proven useful for the study of developmental toxicity. Here, we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC)-based neurodevelopmental toxicity test (hESTn). During neural differentiation the cells were

  20. Correlation between adherence of children epilepsy patients and effect of carbamazepine%儿童癫痫患者卡马西平疗效与依从性的关系

    Institute of Scientific and Technical Information of China (English)

    何晓静

    2013-01-01

    目的 评估癫痫患儿卡马西平(CBz)疗效与依从性的关系.方法 通过查阅病历、问卷调查等方式,对2008年1月至今在我院门诊、病房首诊的癫痫患儿383例进行分析,评价CBZ治疗依从性与疗效的关系.结果 CBZ治疗依从性与疗效相关,规律服药和复查的癫痫患儿疗效显著升高(P<0.05);治疗时间延长,CBZ治疗依从性降低;血药浓度监测可提高CBZ治疗依从性,CBZ浓度在治疗窗内的癫痫患儿依从性较高.结论 癫痫患儿CBZ疗效与依从性密切相关.%Objective To evaluate the correlation between adherence of children epilepsy patients and effect of carbamazeping ( CBZ) , and analyze the main reasons. Methods By looking up medical records, sending out questionnaires, and et al, 383 children epilepsy patients were enrolled in our study from Jan 2008 till now. Using retrospective method, the correlation between adherence of children epilepsy patients and effect of CBZ were analyzed. Results There is a significant correlation between adherence of children epilepsy patients and effect of CBZ. Compared with those who don' t take CBZ and re - check regularly, children epilepsy patients who take CBZ and re — check regularly have significant better result ( P < 0. 05 ) . When duration is longer, adherence of children epilepsy patients is decreased. Adherence of children epilepsy patients is increased in those who take therapeutic drug monitoring. Conclusion Effect of CBZ has a significant correlation with adherence of children epilepsy patients. Clinical pharmacists could help parents of children epilepsy patient improve their recognition, boost the effect of CBZ in children epilepsy patients.

  1. The effect of carbamazepine on the serum lipids of epilepsy children%卡马西平对癫痫患儿血脂的影响(附31例报告)

    Institute of Scientific and Technical Information of China (English)

    温兆春; 孙玉玲; 邹秋萍

    2002-01-01

    选择仅使用卡马西平治疗,且无其他系统疾病及长期服用药物史,无代谢性疾病及早期动脉硬化家族史的癫痫患儿31例,分别测定治疗前、治疗后2个月末、6个月末时的血甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、TC/HDL、LDL/HDL,并进行自身的比较.结果:服用卡马西平后第2个月末较服用前TG、TC、LDL明显增加(P<0.05);服用第2个月末与第6个月末TC、LDL的水平无明显的变化,TG在第6个月末又基本恢复到服药前的水平;TC/HDL、LDL/HDL仅在第6个月末时较服用前有明显增加.认为应用卡马西平治疗超过6个月时,血TC、LDL、LDL/HDL、TC/HDL的变化是明显的,可能过早的导致动脉粥样硬化.

  2. 卡马西平口腔速崩片处方筛选和制备工艺研究%The study on orally disintegrating tablets of Carbamazepine

    Institute of Scientific and Technical Information of China (English)

    苏金龙; 马永恒; 焦海胜; 李敏; 卫晓晓

    2010-01-01

    目的 为了方便老人、儿童和吞咽困难的患者服药,提高卡马西平的生物利用度,优化处方制备卡马西平口腔速崩片(CBZ-ODT).方法 筛选恰当的崩解时间测定方法,以崩解时间和口感为主要评价指标,通过实验选择最佳制备工艺及配方,并通过单因素试验选取对崩解时间影响大的成分的含量为变量进行三因素四水平的L16(43)正交试验设计,确定最优处方.结果 采用全粉末直接压片法,用乳糖作为填充剂,硬脂酸镁做为润滑剂,交联羧甲基纤维素钠(CCNa)作为崩解剂,以崩解时间、硬度和口感为评价指标筛选出最佳处方组合压制三批卡马西平口腔速崩片,片面光洁圆整,无斑点,经测试,崩解时间在(21±3)s.结论 采用全粉末直接压片法压片,工艺简单且能满足要求.采用崩解仪改良法测量崩解时间更为接近于人体口腔内的测定结果,所制备的卡马西平口腔崩解片崩解时间短,硬度适中.口感好,具备临床应用价值.

  3. Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability

    Directory of Open Access Journals (Sweden)

    Marko Krstić

    2015-08-01

    Full Text Available The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD, solid self-microemulsifying drug delivery systems (S-SMEDDS and solid self-nanoemulsifying drug delivery systems (S-SNEDDS were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin® UFL2 was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin® UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6 were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.

  4. Combined application of mixture experimental design and artificial neural networks in the solid dispersion development.

    Science.gov (United States)

    Medarević, Djordje P; Kleinebudde, Peter; Djuriš, Jelena; Djurić, Zorica; Ibrić, Svetlana

    2016-01-01

    This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q10) and 20 (Q20) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.

  5. ANTIEPILEPTIC MEDICATION IN PREGNANCY - LATE EFFECTS ON THE CHILDRENS CENTRAL-NERVOUS-SYSTEM DEVELOPMENT

    NARCIS (Netherlands)

    VANDERPOL, MC; HADDERSALGRA, M; HUISJES, HJ; TOUWEN, BCL

    1991-01-01

    In a follow-up study long-term effects of antenatal exposure to two anticonvulsant drugs, phenobarbital and carbamazepine on central nervous system development were evaluated. Children aged 6 to 13 years of epileptic mothers who used phenobarbital (n = 13), carbamazepine (n = 12), phenobarbital plus

  6. 卡马西平对青霉素点燃惊厥大鼠脑内GABAA受体mRNA表达的作用%The effects of carbamazepine on GABAA receptor mRNA expression in brain of convulsant rats kindled by penicillin

    Institute of Scientific and Technical Information of China (English)

    牛晓军; 马永刚; 王明正; 杨李华; 陈靖京; 张琴琴; 王华坤

    2008-01-01

    目的 研究两种剂量卡马西平对青霉素慢性点燃大鼠的抗惊厥作用及对脑内GABAA受体mRNA表达的影响,从基因水平探讨卡马西平抗惊厥的作用机制.方法 采用腹腔注射(ip)青霉素(3×106 U·kg-1·d-1)慢性点燃大鼠惊厥模型,两种剂量卡马西平(50,100 mg·kg-1×13 d)ig给药,以痫性发作潜伏期和Racine惊厥行为分级标准为判定药效指标,观察卡马西平的抗惊厥作用.运用RT-PCR技术测定大鼠脑内GABAA受体mRNA表达量,分析卡马西平抗惊厥作用的新机制.结果 两种剂量卡马西平ig给药后,均可使青霉素慢性点燃大鼠痫性发作的潜伏期延长,与模型对照组相比差异有统计学意义(P<0.01),同时使惊厥大鼠的发作程度均较模型对照组减轻.青霉素慢性点燃大鼠脑内GABAA受体mRNA表达减少,与正常对照组比较,差异有统计学意义(P<0.01);两种剂量卡马西平预防性干预组的GABAA受体mRNA表达量分别与模型对照组相比,差异均无显著性.结论 两种剂量卡马西平对青霉素慢性点燃的惊厥发作均有明显的对抗作用,但抗惊厥机制与GABAA受体的基因表达无关.

  7. 高效毛细管电泳与荧光偏振免疫法测定癫癇患者血清卡马西平的方法学比较%Determine the Serum Concentration of Carbamazepine in Patients with Epilepsia by HPCE and FPIA

    Institute of Scientific and Technical Information of China (English)

    谢华; 王荣; 贾正平; 徐丽婷; 朱芳丽; 王娟

    2010-01-01

    目的 建立高效毛细管电泳(HPCE)法测定癫痢患者血清卡马西平浓度,比较HPCE法和荧光偏振免疫方法 (FPIA)分析卡马西平含量的差异性.方法 HPCE法采用石英毛细管柱(27 cm×75μm),运行电压18 kV,温度30℃,紫外检测波长280 nm,以30 mmol·L-1磷酸氢二钠(pH=8.0)含75 mmol·L-1十二烷基硫酸钠(SDS)为缓冲液,血样经乙酸乙酯提取后氮气吹干,再用运行缓冲液溶解,压力进样10s.FPIA分析采用标准TDx测定方法 .结果 HPCE方法 测定卡马西平在2.188~100.000μg·mL-1浓度范围内线性关系良好(r=0.998 9),日内和日间RSD均≤5%.结论 HPCE方法 准确、简便、快速,与FPIA检测结果 差异无显著性,因其监测成本低更适用于常规血药监测.

  8. A pharmacological study in the kindling model of epilepsy.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-10-01

    The anticonvulsant properties of carbamazepine were evaluated in the kindled amygdaloid seizure model in rats. Carbamazepine significantly raised the threshold for seizures, reduced the duration of elicited afterdischarges and attenuated the severity of seizures in previously-kindled rats, at doses that did not cause sedation or ataxia. A similar reduction in the duration of elicited afterdischarges and severity of seizures was seen after suprathreshold stimulation (400 mu A) with doses of carbamazepine that were without obvious sedative or ataxic effects. After acute intraperitoneal injections (solvent = 2% Tween-80 and 70% propylene glycol), the maximum anticonvulsant effectiveness against suprathreshold stimulation was seen at 30 min. When administered daily (13 days) during acquisition or development of kindling, carbamazepine (25 and 50 mg/kg, i.p.) had variable effects on kindling. Neither dose consistently reduced the duration of elicited afterdischarges during the acquisition phase. Both groups tended to reduce the developing seizure, with the smaller dose of carbamazepine (25 mg/kg) resulting in a more consistent and significant reduction in severity of seizures. No significant differences in number of daily stimulations needed to reach fully kindled seizures were found. Previous studies have reported variable results with carbamazepine and the kindled amygdaloid seizure in rats. The present study provides a comprehensive evaluation of carbamazepine in this model of epilepsy and discusses the results with regard to the finding reported previously.

  9. Successful treatment of paroxysmal tonic spasms with topiramate in a patient with neuromyelitis optica.

    Science.gov (United States)

    Iida, Shin; Nakamura, Masataka; Wate, Reika; Kaneko, Satoshi; Kusaka, Hirofumi

    2015-09-01

    A 49-year-old woman with neuromyelitis optica (NMO) developed severe quadriplegia and frequent paroxysmal tonic spasms (PTS). Carbamazepine, although initially effective against PTS, caused drug eruption and she was unable to continue. PTS re-emerged after discontinuation of carbamazepine and hindered rehabilitation. Then topiramate was started, and PTS promptly disappeared. The patient became able to resume rehabilitation and her activity of daily life improved significantly. Carbamazepine and topiramate have a common pharmacological action to block voltage-gated sodium channels. The action may have contributed to inhibition of ephaptic transmission in the demyelinating lesions by NMO and eventually improved PTS.

  10. Tacrolimus

    Science.gov (United States)

    ... as indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir); lansoprazole (Prevacid); certain medications for seizures such as carbamazepine ( ... increase the risk that you will develop skin cancer. Protect yourself from skin cancer by avoiding unnecessary ...

  11. Tacrolimus Injection

    Science.gov (United States)

    ... as indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir); lansoprazole (Prevacid); certain medications for seizures such as carbamazepine ( ... increase the risk that you will develop skin cancer. Protect yourself from skin cancer by avoiding unnecessary ...

  12. Tiagabine

    Science.gov (United States)

    ... Tiagabine is in a class of medications called anticonvulsants. It is not known exactly how tiagabine works, ... mention any of the following: amiodarone (Cordarone, Pacerone);anticonvulsants such as carbamazepine (Tegretol), ethosuximide (Zarontin), gabapentin (Neurontin), ...

  13. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn: An update

    OpenAIRE

    2010-01-01

    QUESTION What is the current evidence regarding the association between hemorrhagic disease of the newborn and maternal use of hepatic enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenobarbitone, topiramate)?

  14. Rat postimplantation embryo culture as a tool for internal dose modelling in embryotoxicity risk assessment

    NARCIS (Netherlands)

    Piersma AH; Verhoef A; Klaassen R; van Eijkeren JCH; Olling M; LEO; LBO

    1997-01-01

    De bruikbaarheid van de postimplantatie embryokweek voor interne dosis-modellering van embryotoxiciteit werd geevalueerd met carbamazepine als modelstof. Blootstelling via het kweekmedium leidde tot neuraalbuisdefecten, en blootstelling via amnionholte of exocoeloom veroorzaakte slechts lokale effe

  15. Impact of carbon-dosing on micro-pollutants removal in MBBR post-denitrification systems

    DEFF Research Database (Denmark)

    Escola Casas, Monica; Torresi, Elena; Plósz, Benedek G.

    , erythromycin and sotalol were moderately removed while diatrizoic acid, iopamidol, carbamazepine and diclofenac showed to be hardly biodegradable. The fact that both reactors gave similar removal rate constants for easily degradable compounds, could suggest that diffusion through the biofilm determined...

  16. Curing the Epilepsies: The Promise of Research

    Science.gov (United States)

    ... and studies suggest a specific increased risk of neural tube defects, such as spina bifida. Prenatal exposure to ... verbal abilities. Carbamazepine may increase the risk of neural tube defects, but this is not a consistent finding. ...

  17. Carbamzepine-induced toxic epidermal necrolysis

    Directory of Open Access Journals (Sweden)

    Nithyananda K Chowta

    2011-01-01

    Full Text Available Toxic epidermal necrolysis (TEN, also known as Lyell′s syndrome, is a widespread life-threatening mucocutaneous disease where there is extensive detachment of the skin and mucous membrane. Many factors involved in the etiology of TEN including adverse drug reactions. Here we are reporting a case of toxic epidermal necrolysis in an adult male patient after receiving carbamazepine in a 38 year old male. On the18th day of carbamazepine, patient developed blisters which first appeared on the trunk, chest and arms. The erythematous rash was covering almost all over the body with epidermal detachment of 70% body surface area. There was loss of eye lashes, congestion of conjunctiva with mucopurulent discharge and exposure keratitis. The clinical impression was TEN induced by carbamazepine. Carbamazepine was stopped immediately. He was treated with high dose intravenous betamethasone and systemic and topical antibiotics. After one month, the progression of the skin lesions halted and he was discharged.

  18. Itraconazole

    Science.gov (United States)

    ... treatment with itraconazole: carbamazepine (Epitol, Tegretol, Teril, others); efavirenz (Sustiva, in Atripla); isoniazid (Laniazid, in Rifamate, in ... depression runny nose and other cold symptoms fever hair loss Some side effects can be serious. If ...

  19. Disease: H00772 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Dib-Hajj S, Meisler MH, Pietrobon D Inherited neuronal ion channelopathies: new windows on complex neurologi... Carbamazepine [DR:D00252] MeSH: C563475 OMIM: 167400 PMID:19005038 (description, gene, drug) Catterall WA,

  20. Isobolographic analysis of interactions between remacemide and conventional antiepileptic drugs in the mouse model of maximal electroshock.

    Science.gov (United States)

    Borowicz, Kinga K; Malek, Robert; Luszczki, Jarogniew J; Ratnaraj, Neville; Patsalos, Philip N; Czuczwar, Stanislaw J

    2007-08-01

    Using the mouse maximal electroshock-induced seizure model, indicative of tonic-clonic seizures in humans, the present study was aimed at characterizing the interaction between remacemide and valproate, carbamazepine, phenytoin, and phenobarbital. Isobolographic analysis indicated additive interactions between remacemide and valproate, carbamazepine, and phenytoin (for all fixed ratios of tested drugs: 1:3, 1:1, and 3:1). Additivity was also observed between remacemide and phenobarbital applied in proportions of 1:1 and 3:1. In contrast, the combination of remacemide and phenobarbital at the fixed-ratio of 1:3 resulted in antagonism. Neither motor performance nor long-term memory was impaired by remacemide or by carbamazepine, phenobarbital, phenytoin, and valproate whether or not these drugs were administered singly or in combination. In combination with remacemide, brain concentrations of carbamazepine, phenobarbital, and phenytoin were increased by 71, 21, and 16%, respectively. Although brain valproate concentrations were unaffected by remacemide co-administration, brain concentrations of remacemide and its active metabolite, desglycinyl-remacemide, were increased by 68 and 162%, respectively. In contrast, phenobarbital co-administration was associated with decreases in brain remacemide (27%) and desglycinyl-remacemide (9%) concentrations, whereas only remacemide concentrations (increased by 131%) were affected by carbamazepine co-administration. In conclusion, significant and desirable pharmacodynamic interactions were observed between remacemide and valproate, carbamazepine, phenytoin, and phenobarbital. However, the concurrent pharmacokinetic interactions associated with remacemide complicate these observations and do not make remacemide a good candidate for adjunctive treatment of epilepsy.

  1. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

    Science.gov (United States)

    Schiebler, Mark; Brown, Karen; Hegyi, Krisztina; Newton, Sandra M; Renna, Maurizio; Hepburn, Lucy; Klapholz, Catherine; Coulter, Sarah; Obregón-Henao, Andres; Henao Tamayo, Marcela; Basaraba, Randall; Kampmann, Beate; Henry, Katherine M; Burgon, Joseph; Renshaw, Stephen A; Fleming, Angeleen; Kay, Robert R; Anderson, Karen E; Hawkins, Phillip T; Ordway, Diane J; Rubinsztein, David C; Floto, Rodrigo Andres

    2015-02-01

    Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection.

  2. The evaluation of physical properties of injection molded systems based on poly(ethylene oxide) (PEO).

    Science.gov (United States)

    Pajander, Jari; Rensonnet, Alexia; Hietala, Sami; Rantanen, Jukka; Baldursdottir, Stefania

    2017-02-25

    The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (Mw) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior. Mw of PEO had the greatest impact on the release rate of both APIs. High Mw resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation.

  3. Effects of emerging contaminants on neurotransmission and biotransformation in marine organisms - An in vitro approach.

    Science.gov (United States)

    Luis, Luis G; Barreto, Ângela; Trindade, Tito; Soares, Amadeu M V M; Oliveira, Miguel

    2016-05-15

    The effects of gold (ionic form and nanoparticles - AuNPs) and pharmaceuticals (carbamazepine and fluoxetine) on enzymes involved in neurotransmission (acetylcholinesterase - AChE) and biotransformation (glutathione S-transferases - GST) were assessed by their incubation with Mytilus galloprovincialis' hemolymph and subcellular fraction of gills, respectively. AuNPs did not alter enzymatic activities unlike ionic gold that inhibited AChE and GST activities at 2.5 and 0.42mg·L(-1), respectively. Carbamazepine inhibited AChE activity at 500mg·L(-1) and fluoxetine at 1000mg·L(-1). GST was inhibited by carbamazepine at 250mg·L(-1) and by fluoxetine at 125mg·L(-1). Increased AChE activity was found in simultaneous exposures to fluoxetine and bovine serum albumin coated AuNPs (BSA-AuNPs). Concerning GST, in the simultaneous exposures, AuNPs revealed protective effects against carbamazepine (citrate and polyvinylpyrrolidone coated) and fluoxetine (citrate and BSA coated) induced inhibition. However, BSA-AuNPs increased the inhibition caused by carbamazepine. AuNPs demonstrated ability to interfere with other chemicals toxicity justifying further studies.

  4. Neuroleptic malignant syndrome: A diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Reshma P Ambulkar

    2012-01-01

    Full Text Available We report the case of a 7-year-old girl operated for craniopharyngioma who developed hyperkalemic cardiac arrest in the post-operative period. She was diagnosed as Neuroleptic malignant syndrome (NMS and the causative drug was carbamazepine. It was essentially a diagnosis of exclusion, and treatment was mainly supportive in form of withdrawal of the neuroleptic medication (carbamazepine and administration of dantrolene and bromocriptine. Although, relatively uncommon, NMS can be fatal. NMS presents a clinical challenge as the patient outcome depends on its prompt recognition and treatment.

  5. Tear Film Break-Up Time: Comparison between Patients using Psychiatric Drugs and Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Parvin Dibajnia

    2014-09-01

    Full Text Available Background: Ocular dryness is a well-recognized adverse side effect of many medications. The purpose of this study was to compare tear film stability between psychiatric patients that use lithium carbonate or carbamazepine and normal cases. Materials and Methods: Tear film break up time test was performed in three groups, 30 patients using lithium carbonate, 30 patients using carbamazepine and 30 normal cases. Values of the TBUTs were compared among groups by the independent t-test. Results: Differences between both of patients and control groups were significant (p<0.0001. Conclusion: The results show that these drugs contribute to decrease of tear film break up time.

  6. Preliminary screening of small-scale domestic wastewater treatment systems for removal of pharmaceutical and personal care products

    DEFF Research Database (Denmark)

    Matamoros, Victor; Arias, Carlos Alberto; Brix, Hans

    2009-01-01

    , two biological sand filters, five horizontal subsurface flow and four vertical flow constructed wetlands. As expected, all systems removed TSS and BOD5 efficiently (>95% removal). The PPCP removal efficiencies exceeded 80% with the exception of carbamazepine, diclofenac and ketoprofen because...

  7. Behandeling van trigeminusneuralgie

    NARCIS (Netherlands)

    Bakker, Nicolaas A; van Dijk, J.M.C.; Wagemakers, Michiel; van der Weide, Hiske L; Beese, Uli; Metzemaekers, Joannes

    2014-01-01

    Classic idiopathic trigeminal neuralgia is characterized by sharp unilateral shooting pain in the distribution of one or more branches of the trigeminal nerve. It involves a diagnosis of exclusion. Initially, therapy consists of medical therapy, preferably with carbamazepine or oxcarbazepine. For pa

  8. Identifying women who might benefit from higher doses of folic acid in pregnancy

    OpenAIRE

    Kennedy, Deborah; Koren, Gideon

    2012-01-01

    Question One of my epileptic patients who takes carbamazepine is planning to become pregnant. She told me that Motherisk advised her to take 5 mg of folic acid daily until the end of the first trimester. Are there other women who need more than the regular dose of folic acid included in prenatal vitamins?

  9. Cognitive Effects of Topiramate and Valproate

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-06-01

    Full Text Available Cognitive and behavioral effects of topiramate (TPM and valproate (VPA as adjunctive therapy with carbamazepine (CBZ were compared in 62 adults (16 to 55 years old with refractory partial seizures, in a randomized, double-blind trial at the Medical College of Georgia, Augusta.

  10. Anticonvulsants.

    Science.gov (United States)

    Hillebrand, Marc; Young, John L.

    1994-01-01

    Anticonvulsants have gained recognition for their beneficial effect in the treatment of aggressive behavior, particularly carbamazepine. Empirical studies of the effectiveness of anticonvulsants in decreasing aggression are reviewed and evaluated, and cost-benefit factors related to the use of anticonvulsants are evaluated. A protocol for the…

  11. Removal of 10-hydroxycarbazepine by plasmapheresis

    DEFF Research Database (Denmark)

    Christensen, J; Balslev, T; Villadsen, J;

    2001-01-01

    with studies on other anticonvulsant medications (carbamazepine, valproic acid, phenobarbital, and phenytoin), indicating that minor fractions (2% to 10%) of body stores of these drugs are depleted during plasmapheresis. The authors conclude that it is unnecessary to adjust the oxcarbazepine dosage when...

  12. Antiepileptic drugs targeting sodium channels: subunit and neuron-type specific interactions

    NARCIS (Netherlands)

    Qiao, X.

    2013-01-01

    Certain antiepileptic drugs (e.g. carbamazepine and lamotrigine) block sodium channels in an use-dependent manner and this mechanism contributes to the anti-convulsant properties of these drugs. There are, however, subtle differences in sodium current blocking properties of the antiepileptic drugs w

  13. Tremor in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Mostert, Jop; Heersema, Dorothea; De Keyser, Jacques

    2007-01-01

    Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide som

  14. Simultaneous activated carbon adsorption within a membrane bioreactor for an enhanced micropollutant removal.

    Science.gov (United States)

    Li, Xueqing; Hai, Faisal I; Nghiem, Long D

    2011-05-01

    Significant adsorption of sulfamethoxazole and carbamazepine to powdered activated carbon (PAC) was confirmed by a series of adsorption tests. In contrast, adsorption of these micropollutants to the sludge was negligible. The removal of these compounds in membrane bioreactor (MBR) was dependent on their hydrophobicity and loading as well as the PAC dosage. Sulfamethoxazole exhibited better removal rate during operation under no or low (0.1g/L) PAC dosage. When the PAC concentration in MBR was raised to 1.0 g/L, a sustainable and significantly improved performance in the removal of both compounds was observed - the removal efficiencies of sulfamethoxazole and carbamazepine increased to 82 ± 11% and 92 ± 15% from the levels of 64 ± 7%, and negligible removal, respectively. The higher removal efficiency of carbamazepine at high (1.0 g/L) PAC dosage could be attributed to the fact that carbamazepine is relatively more hydrophobic than sulfamethoxazole, which subsequently resulted in its higher adsorption affinity toward PAC.

  15. Degradation of plant cuticles in soils: impact on formation and sorptive ability of humin-mineral matrices.

    Science.gov (United States)

    Olshansky, Yaniv; Polubesova, Tamara; Chefetz, Benny

    2015-05-01

    Plant cuticles are important precursors for soil organic matter, in particular for soil humin, which is considered an efficient sorbent for organic pollutants. In this study, we examined degradation and transformation of cuticles isolated from fruit and leaves in loamy sand and sandy clay loessial arid brown soils. We then studied sorption of phenanthrene and carbamazepine to humin-mineral matrices isolated from the incubated soils. Low degradation (22%) was observed for agave cuticle in a sandy clay soil system, whereas high degradation (68-78%) was obtained for agave cuticle in a loamy sand soil system and for loamy sand and sandy clay soils amended with tomato cuticle. During incubation, most of the residual organic matter was accumulated in the humin fraction. Sorption of phenanthrene was significantly higher for humin-mineral matrices obtained from soils incubated with plant cuticles as compared with soils without cuticle application. Sorption of carbamazepine to humin-mineral matrices was not affected by cuticle residues. Cooperative sorption of carbamazepine on humin-mineral matrices isolated from sandy clay soil is suggested. Sorption-desorption hysteresis of both phenanthrene and carbamazepine was lower for humin-mineral matrices obtained from soils incubated with plant cuticles as compared with nonamended soils. Our results show that cuticle composition significantly affects the rate and extent of cuticle degradation in soils and that plant cuticle application influences sorption and desorption of polar and nonpolar pollutants by humin-mineral matrices.

  16. The removal of microorganisms and organic micropollutants from wastewater during infiltration to aquifers after irrigation of farmland in the Tula Valley, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Alma; Maya, Catalina [Instituto de Ingenieria, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, 04510 D.F. (Mexico); Gibson, Richard [Instituto de Geografia, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, 04510 D.F. (Mexico); Jimenez, Blanca, E-mail: bjimenezc@iingen.unam.mx [Instituto de Ingenieria, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, 04510 D.F. (Mexico)

    2011-05-15

    The Tula Valley receives untreated wastewater from Mexico City for agricultural irrigation, half of which infiltrates to aquifers from where drinking water is extracted. Samples of wastewater and infiltrated water from three areas of the valley were analyzed for microorganisms, organic micropollutants, and some basic parameters. Concentrations of microorganisms in the infiltrated water were generally very low but the incidence of fecal coliforms (present in 68% of samples), somatic bacteriophages (36%), Giardia spp. (14%), and helminth eggs (8%) suggested a health risk. Organic micropollutants, often present at high concentrations in the wastewater, were generally absent from the infiltrated water except carbamazepine which was in 55% of samples (up to 193 ng/L). There was no correlation between carbamazepine concentrations and the presence of microorganisms but highest concentrations of carbamazepine and boron coincided. A treatment such as nanofiltration would be necessary for the infiltrated water to be a safe potable supply. - Highlights: > Wastewater from Mexico City used for crop irrigation infiltrates to aquifers. > Infiltration through the soil removes many contaminants. > Occasional contamination of infiltrated water with microorganisms occurs. > Carbamazepine is widely present in the infiltrated water. > Safe use of this water for drinking would need nanofiltration or another treatment. - Water extracted from aquifers fed by wastewater used for irrigation may contain microorganisms and persistent polar organic micropollutants and requires treatment to be a potable supply.

  17. Impact of carbon dosing on micro-pollutants removal in MBBR post-denitrification systems

    DEFF Research Database (Denmark)

    Escola, Monica; Torresi, Elena; Gy Plósz, Benedek

    ) with removal rate constants ranging from 0.7 to 2.3 L gTSS -1d-1. Finally, diatrizoic acid, iopamidol, carbamazepine and diclofenac showed to be hardly biodegradable. The fact that both reactors gave similar removal rate constants for easily degradable compounds, suggests that diffusion through the biofilm...

  18. Extending the BSM platform with occurrence, transport and fate of micro-pollutants using the ASM-X framework

    DEFF Research Database (Denmark)

    Flores-Alsina, Xavier; Plósz, Benedek; Lindblom, Erik

    , oxygen concentration and total suspended solids (TSS) loading might have a strong effect on the concentration and the dynamic behaviour of SMX and its metabolites. The second case study presents the fate of tetracycline (TCY), ciprofloxacin (CIP), diclofenac (DCF) and carbamazepine (CMZ) in the benchmark...

  19. Acne keloidalis-like lesions on the scalp associated with antiepileptic drugs.

    Science.gov (United States)

    Grunwald, M H; Ben-Dor, D; Livni, E; Halevy, S

    1990-10-01

    A man developed acne keloidalis-like lesions in the scalp during treatment with diphenylhydantoin and carbamazepine for epilepsy. These drugs were suspected to play a role in the pathogenesis of this skin disease in an unusual location, based on clinical evidence and on the in vitro test, mast cell degranulation (MCD).

  20. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

    LENUS (Irish Health Repository)

    Campbell, E

    2014-09-01

    Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.

  1. New Treatments for Drug-Resistant Epilepsy that Target Presynaptic Transmitter Release

    Science.gov (United States)

    2014-07-01

    pharmacological tools to investigate the effects of levetiracetam, topiramate and carbamazepine on excitatory ( glutamatergic ) synaptic transmission and...discovered that levetiracetam was more effective in reducing the frequency of excitatory synaptic transmission onto dentate granule cells in slices from...functional and structural reorganization of neuronal circuits leads to both hyperexcitability of glutamatergic neurons and defective inhibition (Mello

  2. Source-specific sewage pollution detection in urban river waters using pharmaceuticals and personal care products as molecular indicators.

    Science.gov (United States)

    Kiguchi, Osamu; Sato, Go; Kobayashi, Takashi

    2016-11-01

    Source-specific elucidation of domestic sewage pollution caused by various effluent sources in an urban river water, as conducted for this study, demands knowledge of the relation between concentrations of pharmaceuticals and personal care products (PPCPs) as molecular indicators (caffeine, carbamazepine, triclosan) and water quality concentrations of total nitrogen (T-N) and total phosphorous (T-P). River water and wastewater samples from the Asahikawa River Basin in northern Japan were analyzed using derivatization-gas chromatography/mass spectrometry. Caffeine, used as an indicator of domestic sewage in the Asahikawa River Basin, was more ubiquitous than either carbamazepine or triclosan (92-100 %). Its concentration was higher than any target compound used to assess the basin:  0.759) reflect the contribution of septic tank system effluents to the lower Asahikawa River Basin. Results of relative molecular indicators in combination with different molecular indicators (caffeine/carbamazepine and triclosan/carbamazepine) and cluster analysis better reflect the contribution of sewage than results obtained using concentrations of respective molecular indicators and cluster analysis. Relative molecular indicators used with water quality parameters (e.g., caffeine/T-N ratio) in this study provide results more clearly, relatively, and quantitatively than results obtained using molecular indicators alone. Moreover, the caffeine/T-N ratio reflects variations of caffeine flux from effluent sources. These results suggest strongly relative molecular indicators are also useful indicators, reflecting differences in spatial contributions of domestic sources for PPCPs in urban areas.

  3. Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.

    LENUS (Irish Health Repository)

    McCormack, Mark

    2012-03-01

    An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.

  4. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes.

    Science.gov (United States)

    Sonmez, Fatma Mujgan; Demir, Ercan; Orem, Asim; Yildirmis, Sermet; Orhan, Fazil; Aslan, Adnan; Topbas, Murat

    2006-01-01

    We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

  5. Comparison of body composition in persons with epilepsy on conventional & new antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Sudhir Chandra Sarangi

    2016-01-01

    Interpretation & conclusions: The alterations observed in body composition with valproic acid in contrast to other AEDs like levetiracetam, carbamazepine and phenytoin could affect treatment response in epilepsy especially in subjects with already altered body composition status like obese and thin frail patients, which needs to be established by prospective studies (CTRI/2013/05/003701.

  6. Neuronal monoamine reuptake inhibitors enhance in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

    OpenAIRE

    Coutaux, A F; Mooney, J. J.; Wirth, D. F.

    1994-01-01

    Chloroquine resistance in Plasmodium falciparum was reversed in vitro by the neuronal monoamine reuptake inhibitors and antidepressants desipramine, sertraline, fluoxetine, and norfluoxetine but not by carbamazepine, an antiseizure and mood-stabilizing tricyclic drug resembling desipramine which only weakly inhibits neuronal monoamine reuptake. These findings have important clinical implications for drug combination therapy.

  7. CLINICAL USE OF ANTIEPILEPTIC DRUGS IN THE MANAGEMENT OF CHRONIC PAIN%抗癫痫药物治疗神经病理性疼痛的对照研究

    Institute of Scientific and Technical Information of China (English)

    赵序利; 许永广; 宋文阁; 傅志俭

    2012-01-01

    目的:回顾性分析卡马西平和加巴喷丁治疗原发性三叉神经痛、带状疱疹以及带状疱疹后遗神经痛的疗效、安全性和不良反应.方法:102位患者进入本研究,比较卡马西平或加巴喷丁治疗前后患者疼痛强度的改变和对睡眠影响的改善;依据药物分类,比较两种药物的副作用和不良反应.结果:卡马西平治疗原发性三叉神经痛起效较加巴喷丁快,二者长期疗效相当;加巴喷丁治疗带状疱疹和带状疱疹后神经痛的疗效优于卡马西平;疗效随治疗时间的延长而增加.卡马西平的副作用和不良反应事件发生率较加巴喷丁高.结论:抗癫痫药物卡马西平和加巴喷丁是治疗神经病理性疼痛的有效药物,可以改善患者的睡眠,但副作用和不良反应发生率高.%Objective: To evaluate the effects, safety and adverse effects of carbamazepine and gabapentin in the treatment of primary trigeminal neuralgia, herpes zoster neuralgia and postherpetic neuralgia. Methods: A total of 102 patients who suffered from primary trigeminal neuralgia, herpes zoster neuralgia and postherpetic neuralgia were assessed with changes in pain and sleep interference improvement after treatment with carbamazepine or gabapentin. The adverse events were evaluated and calculated between the carbamazepine and gabapentin. Results: Both carbamazepine and gabapentin had the same long term effects on trigeminal neuralgia, but carbamazepine got a rapid analgesia and sleep improvement effect than gabapentin. Gabapentin was more effective than carbamazepine in controlling pain and in improving sleep interference caused by herpes zoster and postherpetic neuralgia. The therapeutic effects was continually improved over time. Carbamazepine caused more adverse events than gabapentin. Conclusion: Antiepileptic drugs were effective in controlling neuropathic pain, and improved patient's sleep interference caused by pain. But they had a high risk in causing

  8. Effects of selected pharmaceuticals on riverine biofilm communities.

    Science.gov (United States)

    Lawrence, John R; Swerhone, George D W; Wassenaar, Leonard I; Neu, Thomas R

    2005-08-01

    Although pharmaceutical and therapeutic products are widely found in the natural environment, there is limited understanding of their ecological effects. Here we used rotating annular bioreactors to assess the impact of 10 microg.L(-1) of the selected pharmaceuticals ibuprofen, carbamazepine, furosemide, and caffeine on riverine biofilms. After 8 weeks of development, community structure was assessed using in situ microscopic analyses, fluor-conjugated lectin binding, standard plate counts, fluorescent in situ hybridization, carbon utilization spectra, and stable carbon isotope analyses. The biofilm communities varied markedly in architecture although only caffeine treated biofilms were significantly thicker. Cyanobacteria were suppressed by all 4 compounds, whereas the nitrogen containing caffeine, furosemide, and carbamazepine increased algal biomass. Ibuprofen and carbamazepine reduced bacterial biomass, while caffeine and furosemide increased it. Exopolymer content and composition of the biofilms was also influenced. Significant positive and negative effects were observed in carbon utilization spectra. In situ hybridization analyses indicated all treatments significantly decreased the gamma-proteobacterial populations and increased beta-proteobacteria. Ibuprofen in particular increased the alpha-proteobacteria, beta-proteobacteria, cytophaga-flavobacteria, and SRB385 probe positive populations. Caffeine and carbamazepine additions resulted in significant increases in the high GC354c and low GC69a probe positive cells. Live-dead analyses of the biofilms indicated that all treatments influenced the ratio of live-to-dead cells with controls having a ratio of 2.4, carbamazepine and ibuprofen being 3.2 and 3.5, respectively, and furosemide and caffeine being 1.9 and 1.7, respectively. Stable isotope analyses of the biofilms indicated delta 13C values shifted to more negative values relative to control biofilms. This shift may be consistent with proportional loss of

  9. Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies

    Science.gov (United States)

    Petersen, Irene; Collings, Shuk-Li; McCrea, Rachel L; Nazareth, Irwin; Osborn, David P; Cowen, Phil J; Sammon, Cormac J

    2017-01-01

    Objective The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy. Patients and methods Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs) using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment. Results In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6%) women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to threefold higher in women prescribed valproate. Conclusion The results of our study suggest that lamotrigine and carbamazepine are safer treatment options than valproate in pregnancy and should be considered as alternative treatment options for women of childbearing potential and in pregnancy. PMID:28243149

  10. Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies

    Directory of Open Access Journals (Sweden)

    Petersen I

    2017-02-01

    Full Text Available Irene Petersen,1,2 Shuk-Li Collings,1,3 Rachel L McCrea,1 Irwin Nazareth,1 David P Osborn,4 Phil J Cowen,5 Cormac J Sammon1 1Department of Primary Care and Population Health, University College London, London, UK; 2Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark; 3OXON Epidemiology, London, UK; 4Division of Psychiatry, University College London, London, UK; 5University Department of Psychiatry, Warneford Hospital, Oxford, UK Objective: The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED treatment in pregnancy.Patients and methods: Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment.Results: In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6% women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to

  11. Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction

    Science.gov (United States)

    Kong, Qingxia; Min, Xia; Sun, Ran; Gao, Jianying; Liang, Ruqing; Li, Lei; Chu, Xu

    2016-01-01

    The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented

  12. Determination of sedative hypnotics in sewage sludge by pressurized liquid extraction with high-performance liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Arbeláez, Paula; Granados, Judith; Borrull, Francesc; Marcé, Rosa Maria; Pocurull, Eva

    2014-12-01

    This paper describes a method for the determination of eight sedative hypnotics (benzodiazepines and barbiturates) in sewage sludge using pressurized liquid extraction and liquid chromatography with tandem mass spectrometry. Pressurized liquid extraction operating conditions were optimized and maximum recoveries were reached using methanol under the following operational conditions: 100ºC, 1500 psi, extraction time of 5 min, one extraction cycle, flush volume of 60% and purge time of 120 s. Pressurized liquid extraction recoveries were higher than 88% for all the compounds except for carbamazepine (55%). The repeatability and reproducibility between days, expressed as relative standard deviation (n = 5), were lower than 6 and 10%, respectively. The detection limits for all compounds were lower than 12.5 μg/kg of dry weight. The method was applied to determine benzodiazepines and barbiturates in sewage sludge from urban sewage treatment plants, and carbamazepine showed the highest concentration (7.9-18.9 μg/kg dry weight).

  13. [Effect of psychotropic drugs on activity of anticonvulsants in maximal electroshock test].

    Science.gov (United States)

    Alikina, N A; Tregubov, A L; Kotegov, V P

    2010-08-01

    The effect ofpsychotropic drugs on the pharmacological properties of anticonvulsants was studied on white mice under maximal electroshock (ME) test conditions. Changes in the anticonvulsant effect of phenobarbital, diphenin, carbamazepine, hexamidine were traced upon their joint administration with psychotropic drugs, including piracetam, aminalon, amitriptyline, imizine, levomepromazine, and lithium oxybutyrate. An important result of research is the fact, that in no one of combinations the basic pharmacological effect of anticonvulsants was decreased. Based on the results of experiments, the most rational combinations of anticonvulsants with psychotropic preparations were revealed as manifested in the ME test. As criterion of rational combination was the increase in the activity of anticonvulsants and reduction of their toxicity in combination or at least invariance of this parameter. Rational combinations include (i) phenobarbital with piracetam, amitriptyline, levomepromazine, and lithium oxybutyrate; (ii) carbamazepine with piracetam; and (iii) hexamidine with amitriptyline, levomepromazine and imizine.

  14. Effects of tricyclic compounds and other drugs having a membrane stabilizing action on analgesia, tolerance to and dependence on morphine.

    Science.gov (United States)

    Contreras, E; Tamayo, L; Quijada, L

    1977-08-01

    Several drugs affecting nerve cell excitability, by opposing ion movements in membranes, were tested in mice rendered tolerant to or dependent on morphine. The purpose of the study was to investigate whether these drugs share the ability to attenuate morphine tolerance and dependence exhibited by tricyclic antidepressants. Tolerance to morphine was decreased by the administration of imipramine, doxepin, promethazine, propranolol, lidocaine and quinidine. Chlorpromazine and carbamazepine were ineffective. The intensity of the abstinence syndrome provoked by naloxone was decreased by chlorpromazine, imipramine, doxepin, lidocaine, quinidine and propranolol. Diphenyl. hydantion and carbamazepine had no effect. The results are discussed in relation with the blockade of ion conductance and their interference with the release of neurotransmitters produced by the drugs assayed.

  15. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

    Science.gov (United States)

    Nguyen, Julia; Ita, Kevin B.; Morra, Matthew J.; Popova, Inna E.

    2016-01-01

    The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h) compared to passive delivery (12.83 ± 6.30 µg/cm2/h). For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h). Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant. PMID:27854292

  16. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Julia Nguyen

    2016-11-01

    Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

  17. Paroxysmal ataxia and dysarthria in multiple sclerosis.

    Science.gov (United States)

    Iorio, R; Capone, F; Plantone, D; Batocchi, A P

    2014-01-01

    Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.

  18. Lamotrigine: Evidence of its utility in the bipolar inconvenience

    OpenAIRE

    Alexánder Pinzón Amado

    2001-01-01

    Anticonvulsants, including valproate and carbamazepine, haveestablished efficacy in the treatment of bipolar disorder (BD).Lamotrigine, a second generation anticonvulsant, has beenreported to have antimanic, antidepressant and mood-stabilizingeffects. There have been published to date several case reports,case series, open trials and two randomized controlled trialswith lamotrigine as monotherapy or as add-on treatment inpatients with BD. Mechanisms of actions proposed to explainthe mood-stab...

  19. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  20. Primary melanoma of Meckel's cave: case report Melanoma primário do cavo de Meckel: relato de caso

    OpenAIRE

    Asdrubal Falavigna; Luis A. B. Borba; Fernando Antonio Patriani Ferraz; Giovana Camargo de Almeida; José Valentim Krindges Júnior

    2004-01-01

    We present a case of trigeminal neuralgia with cranial normal magnetic resonance image (MRI) and computed tomography. The pain was not relieved by carbamazepine and microvascular decompression surgery was done. After two months the pain was similar to the condition before surgery. At this time, MRI showed an expansive lesion in Meckel's cave that was treated with radical resection by extra-dural approach. The pathologic examination revealed a primary melanoma. The follow-up after six months d...

  1. Primary melanoma of Meckel's cave: case report.

    Science.gov (United States)

    Falavigna, Asdrubal; Borba, Luis A B; Ferraz, Fernando Antonio Patriani; Almeida, Giovana Camargo de; Krindges Júnior, José Valentim

    2004-06-01

    We present a case of trigeminal neuralgia with cranial normal magnetic resonance image (MRI) and computed tomography. The pain was not relieved by carbamazepine and microvascular decompression surgery was done. After two months the pain was similar to the condition before surgery. At this time, MRI showed an expansive lesion in Meckel's cave that was treated with radical resection by extra-dural approach. The pathologic examination revealed a primary melanoma. The follow-up after six months did not show abnormalities.

  2. Primary melanoma of Meckel's cave: case report

    OpenAIRE

    Falavigna,Asdrubal; Luis A. B. Borba; Ferraz, Fernando Antonio Patriani [UNIFESP; Almeida,Giovana Camargo de; Krindges Júnior,José Valentim

    2004-01-01

    We present a case of trigeminal neuralgia with cranial normal magnetic resonance image (MRI) and computed tomography. The pain was not relieved by carbamazepine and microvascular decompression surgery was done. After two months the pain was similar to the condition before surgery. At this time, MRI showed an expansive lesion in Meckel's cave that was treated with radical resection by extra-dural approach. The pathologic examination revealed a primary melanoma. The follow-up after six months d...

  3. Stevens-Johnson syndrome limited to multiple sites of radiation therapy in a patient receiving phenobarbital.

    Science.gov (United States)

    Duncan, K O; Tigelaar, R E; Bolognia, J L

    1999-03-01

    Stevens-Johnson syndrome (SJS) is a severe cutaneous eruption that most often appears as an adverse reaction to a medication. There have been 21 reported cases of atypical erythema multiforme, toxic epidermal necrolysis, and SJS arising in patients receiving radiation therapy in addition to phenytoin, phenobarbital, or carbamazepine. We report the second case of SJS resulting from concomitant phenobarbital and radiation therapy, in which the eruption was limited to the sites of radiation, which were multiple.

  4. Combined symptomatology of psychosis, pica syndrome, and hippocampal sclerosis: a case report.

    Science.gov (United States)

    Rohde, Judith; Claussen, Malte Christian; Kuechenhoff, Bernhard; Seifritz, Erich; Schuepbach, Daniel

    2013-01-01

    Pica is the developmentally and culturally inappropriate eating of nonnutritive substances for at least 1 month. Herein, we present the case of a male patient that suddenly showed behavioral changes including aggressiveness, withdrawal, and perceptional disturbances at the age of 12. About 7 years later, pica symptoms emerged additionally. Neither pharmacotherapy nor electroconvulsive therapy led to success. Magnetic resonance imaging showed bilateral sclerosis of the hippocampus. The therapy with carbamazepine, clozapine, diazepam, and zinc finally improved the symptoms including the pica symptoms.

  5. An ex Vivo Model for Evaluating Blood-Brain Barrier Permeability, Efflux, and Drug Metabolism

    DEFF Research Database (Denmark)

    Hellman, Karin; Aadal Nielsen, Peter; Ek, Fredrik

    2016-01-01

    , risperidone, citalopram, fluoxetine, and haloperidol were studied, and one preselected metabolite for each drug was analyzed, identified, and quantified. Metabolite identification studies of clozapine and midazolam showed that the locust brain was highly metabolically active, and 18 and 14 metabolites......, respectively, were identified. The unbound drug fraction of clozapine, NDMC, carbamazepine, and risperidone was analyzed. In addition, coadministration of drugs with verapamil or fluvoxamine was performed to evaluate drug-drug interactions in all setups. All findings correlated well with the data...

  6. Nanosuspension: An approach to enhance solubility of drugs

    OpenAIRE

    Patel, Vishal R.; Y K Agrawal

    2011-01-01

    One of the major problems associated with poorly soluble drugs is very low bioavailability. The problem is even more complex for drugs like itraconazole, simvastatin, and carbamazepine which are poorly soluble in both aqueous and nonaqueous media, belonging to BCS class II as classified by biopharmaceutical classification system. Formulation as nanosuspension is an attractive and promising alternative to solve these problems. Nanosuspension consists of the pure poorly water-soluble drug witho...

  7. Antiepileptic drug poisoning: Three-year experience

    Directory of Open Access Journals (Sweden)

    Yahya Kemal Günaydın

    2015-01-01

    Conclusion: First generation antiepileptics are more toxic than SGAEs. In patients with serum carbamazepine level, particularly those over 30 mg/L, serious disorders of consciousness, cardiovascular toxicity, and metabolic disorders may occur. In VPA intoxication, there is a positive correlation between the serum VPA levels and ammonia levels. On account of this finding, one should be more careful about hyperammonemic hepatic encephalopathy as the serum VPA level rises.

  8. Stevens-Johnson syndrome induced by phenytoin: a case report

    Directory of Open Access Journals (Sweden)

    Lalkota Prakash Bhanu

    2016-12-01

    Full Text Available Stevens-Johnson syndrome (SJS and Toxic epidermal necrolysis (TEN are rare (one to two per 10,00,00 population per year but life threatening adverse drug reactions. Antiepileptic drugs-induced Stevens-Johnson syndrome (SJS is a life-threatening severe cutaneous adverse reaction, amongst anti-epileptics; carbamazepine and phenytoin are the major culprits. We report here a case of SJS due to phenytoin (CTC vs 2 Grade 3.

  9. Using modified Kramers-Kronig relations to test transmission spectra of porous media in THz-TDS.

    Science.gov (United States)

    Tuononen, H; Gornov, E; Zeitler, J A; Aaltonen, J; Peiponen, K-E

    2010-03-01

    We show that modified Kramers-Kronig relations provide a useful tool to test the validity of the complex refractive index extracted from transmission terahertz spectra of porous matrices containing pharmaceutical materials. The role of scattering of terahertz radiation is qualitatively considered as a reason for the observed discrepancy between experimental data and the values extracted from the inverted complex refractive index. As an example we present an analysis of the terahertz spectra of carbamazepine and lactose alpha-monohydrate.

  10. Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies

    Science.gov (United States)

    Ying, Guang-Guo; Kookana, Rai S.; Kolpin, Dana W.

    2009-01-01

    Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

  11. Occipital seizures presenting with bilateral visual loss

    Directory of Open Access Journals (Sweden)

    Hadjikoutis S

    2003-01-01

    Full Text Available Transient visual loss may occur with occipital seizures as an ictal or post-ictal phenomenon. Its duration varies from less than one minute to days, or can be permanent. We describe a 61-year-old man presenting with headache, vomiting and bilateral visual loss. EEG revealed persistent spike discharge in the occipital lobes suggesting occipital seizures. His vision improved with carbamazepine.

  12. Modulation of trichloroethylene in vitro metabolism by different drugs in human.

    Science.gov (United States)

    Cheikh Rouhou, Mouna; Haddad, Sami

    2014-08-01

    Toxicological interactions with drugs have the potential to modulate the toxicity of trichloroethylene (TCE). Our objective is to identify metabolic interactions between TCE and 14 widely used drugs in human suspended hepatocytes and characterize the strongest using microsomal assays. Changes in concentrations of TCE and its metabolites were measured by headspace GC-MS. Results with hepatocytes show that amoxicillin, cimetidine, ibuprofen, mefenamic acid and ranitidine caused no significant interactions. Naproxen and salicylic acid showed to increase both TCE metabolites levels, whereas acetaminophen, carbamazepine and erythromycin rather decreased them. Finally, diclofenac, gliclazide, sulphasalazine and valproic acid had an impact on the levels of only one metabolite. Among the 14 tested drugs, 5 presented the most potent interactions and were selected for confirmation with microsomes, namely naproxen, salicylic acid, acetaminophen, carbamazepine and valproic acid. Characterization in human microsomes confirmed interaction with naproxen by competitively inhibiting trichloroethanol (TCOH) glucuronidation (Ki=2.329 mM). Inhibition of TCOH formation was also confirmed for carbamazepine (partial non-competitive with Ki=70 μM). Interactions with human microsomes were not observed with salicylic acid and acetaminophen, similar to prior results in rat material. For valproic acid, interactions with microsomes were observed in rat but not in human. Inhibition patterns were shown to be similar in human and rat hepatocytes, but some differences in mechanisms were noted in microsomal material between species. Next research efforts will focus on determining the adequacy between in vitro observations and the in vivo situation.

  13. Management issues for women with epilepsy--focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

    Science.gov (United States)

    Harden, Cynthia L; Pennell, Page B; Koppel, Barbara S; Hovinga, Collin A; Gidal, Barry; Meador, Kimford J; Hopp, Jennifer; Ting, Tricia Y; Hauser, W A; Thurman, David; Kaplan, Peter W; Robinson, Julian N; French, Jacqueline A; Wiebe, Samuel; Wilner, Andrew N; Vazquez, Blanca; Holmes, Lewis; Krumholz, Allan; Finnell, Richard; Shafer, Patricia O; Le Guen, Claire L

    2009-05-01

    A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

  14. Evaluation of anticonvulsants for possible use in neuropathic pain.

    Science.gov (United States)

    Waszkielewicz, A M; Gunia, A; Słoczyńska, K; Marona, H

    2011-01-01

    Neuropathic pain is a kind of pain related with functional abnormality of neurons. Despite large progress in pharmacotherapy, neuropathic pain is still considered an unmet need. Nowadays, there are few drugs registered for this condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known antiepileptic drugs. Among the group of new antiepileptic drugs, which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development. Therefore, it is already a phenomenon that researchers turn their projects toward a larger market, related with possible similar mechanism. Anticonvulsant mechanism of action is in the first place among primary indications for drugs revealing potential analgesic activity. Therefore, many drug candidates for epilepsy, still in preclinical stage, are being evaluated for activity in neuropathic pain. This review is focusing on antiepileptic drugs, which are evaluated for their analgesic activity in major tests related with neuropathic pain. Relation between structure, mechanism of action and result in tests such as the Chung model (spinal nerve ligation SNL), the Bennett model (chronic constriction injury of sciatic nerve CCI) and other tests are considered. The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc. Moreover, clinical efficacy related with listed animal models has been discussed.

  15. Influence of organic surface coatings on the sorption of anticonvulsants on mineral surfaces.

    Science.gov (United States)

    Qu, Shen; Cwiertny, David M

    2013-10-01

    Here, we explore the role that sorption to mineral surfaces plays in the fate of two commonly encountered effluent-derived pharmaceuticals, the anticonvulsants phenytoin and carbamazepine. Adsorption isotherms and pH-edge experiments are consistent with electrostatics governing anticonvulsant uptake on metal oxides typically found in soil and aquifer material (e.g., Si, Al, Fe, Mn, and Ti). Appreciable, albeit limited, adsorption was observed only for phenytoin, which is anionic above pH 8.3, on the iron oxides hematite and ferrihydrite. Adsorption increased substantially in the presence of cationic and anionic surfactants, species also commonly encountered in wastewater effluent. For carbamazepine, we propose the enhanced uptake results entirely from hydrophobic interactions with apolar tails of surfactant surface coatings. For phenytoin, adsorption also arises from the ability of surfactants to alter the net charge of the mineral surface and thereby further enhance favorable electrostatic interactions with its anionic form. Collectively, our results demonstrate that although pristine mineral surfaces are likely not major sinks for phenytoin and carbamazepine in the environment, their alteration with organic matter, particularly surfactants, can considerably increase their ability to retain these emerging pollutants in subsurface systems.

  16. Mexiletine and its Interactions with Classical Antiepileptic Drugs: An Isobolographic Analysis.

    Science.gov (United States)

    Borowicz-Reutt, Kinga K; Banach, Monika; Piskorska, Barbara

    2016-05-01

    Using the mouse maximal electroshock test, the reference model of tonic-clonic seizures, the aim of the present study was to determine the type of interaction between mexiletine (a class IB antiarrhythmic drug) and classical antiepileptics: valproate, carbamazepine, phenytoin, and phenobarbital. Isobolographic analysis of obtained data indicated antagonistic interactions between mexiletine and valproate (for fixed ratio combinations of 1:1 and 3:1). Additivity was observed between mexiletine and valproate applied in proportion of 1:3 as well as between mexiletine and remaining antiepileptics for the fixed ratios of 1:3, 1:1, and 3:1. Neither motor performance nor long-term memory were impaired by mexiletine or antiepileptic drugs regardless of whether they were administered singly or in combination. Mexiletine did not significantly affected brain concentrations of carbamazepine, phenobarbital or phenytoin. In contrast, the antiarrhythmic drug decreased by 23 % the brain level of valproate. This could be, at least partially, the reason of antagonistic interaction between the two drugs. In conclusion, the observed additivity suggests that mexiletine can be safely applied in epileptic patients treated with carbamazepine, phenytoin or phenobarbital. Because of undesirable pharmacodynamics and pharmacokinetic interactions with valproate, mexiletine should not be used in such combinations.

  17. Interactions between non-barbiturate injectable anesthetics and conventional antiepileptic drugs in the maximal electroshock test in mice--an isobolographic analysis.

    Science.gov (United States)

    Borowicz, Kinga K; Łuszczki, Jarogniew; Czuczwar, Stanisław J

    2004-03-01

    The aim of this study was the isobolographic evaluation of interactions between three non-barbiturate intravenous anesthetics and conventional antiepileptic drugs in the maximal electroshock-induced seizures in mice. Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Plasma levels of antiepileptic drugs were measured by immunofluorescence. Obtained results indicate that ketamine acts synergistically with valproate and carbamazepine. Also the combinations of propofol and valproate or phenobarbital led to synergistic interactions. An antagonism was found between etomidate and carbamazepine or phenobarbital. On the other hand, interactions between diphenylhydantoin and injectable anesthetics proved to be additive. The only exception was the combination of diphenylhydantoin and propofol (1:3). Pharmacokinetic phenomena do not seem to interfere with the observed interactions, since none of anesthetics influenced the free plasma concentrations of antiepileptic drugs. Referring to undesired effects, only propofol impaired long-term memory. Although propofol did not disturbed motor coordination, it enhanced motor impairment caused by carbamazepine and diphenylhydantoin. Results of the present study suggest that etomidate needs to be avoided in epileptic patients due to a possibility of negative interactions with some antiepileptic drugs and seizure precipitation.

  18. Effects of Various Antiepileptics Used to Alleviate Neuropathic Pain on Compound Action Potential in Frog Sciatic Nerves: Comparison with Those of Local Anesthetics

    Directory of Open Access Journals (Sweden)

    Yuhei Uemura

    2014-01-01

    Full Text Available Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na+ and Ca2+ channels, glutamate-receptor inhibition, and GABAA-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine concentration dependently reduced the peak amplitude of the CAP (IC50=0.44 and 0.50 mM, resp.. Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50=0.23 mM. These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.

  19. Fate of pharmaceutical compounds in hydroponic mesocosms planted with Scirpus validus.

    Science.gov (United States)

    Zhang, Dong Qing; Gersberg, Richard M; Hua, Tao; Zhu, Junfei; Goyal, Manish Kumar; Ng, Wun Jern; Tan, Soon Keat

    2013-10-01

    A systematic approach to assess the fate of selected pharmaceuticals (carbamazepine, naproxen, diclofenac, clofibric acid and caffeine) in hydroponic mesocosms is described. The overall objective was to determine the kinetics of depletion (from solution) and plant uptake for these compounds in mesocosms planted with S. validus growing hydroponically. The potential for translocation of these pharmaceuticals from the roots to the shoots was also assessed. After 21 days of incubation, nearly all of the caffeine, naproxen and diclofenac were eliminated from solution, whereas carbamazepine and clofibric acid were recalcitrant to both photodegradation and biodegradation. The fact that the BAFs for roots for carbamazepine and clofibric acid were greater than 5, while the BAFs for naproxen, diclofenac and caffeine were less than 5, implied that the latter two compounds although recalcitrant to biodegradation, still had relatively high potential for plant uptake. Naproxen was sensitive to both photodegradation (30-42%) and biodegradation (>50%), while diclofenac was particularly sensitive (>70%) to photodegradation alone. No significant correlations (p > 0.05) were found between the rate constants of depletion or plant tissue levels of the pharmaceuticals and either log Kow or log Dow.

  20. Mechanisms of human motor cortex facilitation induced by subthreshold 5-Hz repetitive transcranial magnetic stimulation.

    Science.gov (United States)

    Sommer, Martin; Rummel, Milena; Norden, Christoph; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

    2013-06-01

    Our knowledge about the mechanisms of human motor cortex facilitation induced by repetitive transcranial magnetic stimulation (rTMS) is still incomplete. Here we used pharmacological conditioning with carbamazepine, dextrometorphan, lorazepam, and placebo to elucidate the type of plasticity underlying this facilitation, and to probe if mechanisms reminiscent of long-term potentiation are involved. Over the primary motor cortex of 10 healthy subjects, we applied biphasic rTMS pulses of effective posterior current direction in the brain. We used six blocks of 200 pulses at 5-Hz frequency and 90% active motor threshold intensity and controlled for corticospinal excitability changes using motor-evoked potential (MEP) amplitudes and latencies elicited by suprathreshold pulses before, in between, and after rTMS. Target muscle was the dominant abductor digiti minimi muscle; we coregistered the dominant extensor carpi radialis muscle. We found a lasting facilitation induced by this type of rTMS. The GABAergic medication lorazepam and to a lesser extent the ion channel blocker carbamazepine reduced the MEP facilitation after biphasic effective posteriorly oriented rTMS, whereas the N-methyl-d-aspartate receptor-antagonist dextrometorphan had no effect. Our main conclusion is that the mechanism of the facilitation induced by biphasic effective posterior rTMS is more likely posttetanic potentiation than long-term potentiation. Additional findings were prolonged MEP latency under carbamazepine, consistent with sodium channel blockade, and larger MEP amplitudes from extensor carpi radialis under lorazepam, suggesting GABAergic involvement in the center-surround balance of excitability.

  1. Antiepileptic drug regimens and major congenital abnormalities in the offspring.

    Science.gov (United States)

    Samrén, E B; van Duijn, C M; Christiaens, G C; Hofman, A; Lindhout, D

    1999-11-01

    To assess the risk of major congenital abnormalities associated with specific antiepileptic drug regimens, a large retrospective cohort study was performed. The study comprised 1,411 children born between 1972 and 1992 in four provinces in The Netherlands who were born to mothers with epilepsy and using antiepileptic drugs during the first trimester of pregnancy, and 2,000 nonepileptic matched controls. We found significantly increased risks of major congenital abnormalities for carbamazepine and valproate monotherapy, with evidence for a significant dose-response relationship for valproate. The risk of major congenital abnormalities was nonsignificantly increased for phenobarbital monotherapy when caffeine comedication was excluded, but a significant increase in risk was found when caffeine was included. Phenytoin monotherapy was not associated with an increased risk of major congenital abnormalities. Regarding polytherapy regimens, increased risks were found for several antiepileptic drug combinations. Clonazepam, in combination with other antiepileptic drugs, showed a significantly increased relative risk. Furthermore, there were significantly increased relative risks for the combination of carbamazepine and valproate and the combination of phenobarbital and caffeine with other antiepileptic drugs. This study shows that most antiepileptic drug regimens were associated with an increased risk of major congenital abnormalities in the offspring, in particular valproate (dose-response relationship) and carbamazepine monotherapy, benzodiazepines in polytherapy, and caffeine comedication in combinations with phenobarbital.

  2. Differential drug effects on spontaneous and evoked pain behavior in a model of trigeminal neuropathic pain

    Science.gov (United States)

    Deseure, K; Hans, GH

    2017-01-01

    Purpose Baclofen and morphine have shown efficacy against mechanical allodynia after infraorbital nerve chronic constriction injury (IoN-CCI). No drug effects have yet been reported on spontaneous trigeminal neuropathic pain. It has been proposed that the directed face grooming behavior that also develops following IoN-CCI offers a measure of spontaneous trigeminal neuropathic pain. Subjects and methods We examined the effects of a continuous 1-week infusion of 30 mg/day carbamazepine (the first-line drug treatment for trigeminal neuralgia), 1.06 mg/day baclofen, 4.18 mg/day clomipramine, and 5 mg/day morphine on spontaneous and mechanically evoked pain behavior (ie, directed face grooming and von Frey testing) in IoN-CCI rats. Results Isolated face grooming was significantly reduced in rats receiving carbamazepine and baclofen but not in clomipramine- or morphine-treated rats. All drugs showed significant antiallodynic effects; carbamazepine showed the strongest effects, whereas clomipramine had only minor efficacy. Conclusion The tested drugs have differential effects in the IoN-CCI model, and different neuropathological mechanisms may underlie the different somatosensory symptoms in this model. A mechanism-based approach may be needed to treat (trigeminal) neuropathic pain. The present data support IoN-CCI as a model of trigeminal neuralgia in which isolated face grooming is used as a measure of spontaneous neuropathic pain. PMID:28184169

  3. Transformation of the antiepileptic drug oxcarbazepine upon different water disinfection processes.

    Science.gov (United States)

    Li, Zhi; Fenet, Hélène; Gomez, Elena; Chiron, Serge

    2011-02-01

    Transformation of the pharmaceutical oxcarbazepine (OXC), a keto analogue of carbamazepine (CBZ) was investigated under different water disinfection processes (ozonation, chlorination and UV irradiation) to compare its persistence, toxicity and degradation pathways with those of CBZ. Analysis by LC-ion trap-MS(n) allowed for the identification of up to thirteen transformation products (TPs). The major abundant and persistent TPs (10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (DiOH-CBZ), acridine (ACIN) and 1-(2-benzaldehyde)-(1H, 3H)-quinazoline-2,4-dione (BQD)) were identical to those previously reported during water treatment of CBZ. Only one new compound arising from an intramolecular cyclisation reaction was identified during UV irradiation. OXC reacted quickly with hydroxyl radical and relatively rapidly with free chlorine while slow reaction rates were recorded in presence of ozone and upon UV irradiation. An increase of the acute toxicity of UV irradiated solutions, monitored by a Daphnia magna bioassay, was recorded, probably due to the accumulation of ACIN. The formation of ACIN is of concern due to the carcinogenic properties of this chemical. ACIN was also generated during the direct UV photo transformation of DiOH-CBZ and 10-hydroxy-10,11-dihydro-carbamazepine (OH-CBZ), two metabolites of OXC and CBZ widely detected in water resources. Analysis of tap water samples revealed the occurrence at ng/L levels of the major TPs detected under laboratory scale experiments, except ACIN.

  4. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    Science.gov (United States)

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species.

  5. The influence of six pharmaceuticals on freshwater sediment microbial growth incubated at different temperatures and UV exposures.

    Science.gov (United States)

    Veach, Allison; Bernot, Melody J; Mitchell, James K

    2012-07-01

    Pharmaceutical compounds have been detected in freshwater for several decades. Once they enter the aquatic ecosystem, they may be transformed abiotically (i.e., photolysis) or biotically (i.e., microbial activity). To assess the influence of pharmaceuticals on microbial growth, basal salt media amended with seven pharmaceutical treatments (acetaminophen, caffeine, carbamazepine, cotinine, ibuprofen, sulfamethoxazole, and a no pharmaceutical control) were inoculated with stream sediment. The seven pharmaceutical treatments were then placed in five different culture environments that included both temperature treatments of 4, 25, 37°C and light treatments of continuous UV-A or UV-B exposure. Microbial growth in the basal salt media was quantified as absorbance (OD(550)) at 7, 14, 21, 31, and 48d following inoculation. Microbial growth was significantly influenced by pharmaceutical treatments (P microbial communities post-incubation identified selection of microbial and fungal species with exposure to caffeine, cotinine, and ibuprofen at 37°C; acetaminophen, caffeine, and cotinine at 25°C; and carbamazepine exposed to continuous UV-A. Bacillus and coccus cellular arrangements (1000X magnification) were consistently observed across incubation treatments for each pharmaceutical treatment although carbamazepine and ibuprofen exposures incubated at 25°C also selected spiral-shaped bacteria. These data indicate stream sediment microbial communities are influenced by pharmaceuticals though physiochemical characteristics of the environment may dictate microbial response.

  6. Seizure susceptibility of neuropeptide-Y null mutant mice in amygdala kindling and chemical-induced seizure models.

    Science.gov (United States)

    Shannon, Harlan E; Yang, Lijuan

    2004-01-01

    Neuropeptide Y (NPY) administered exogenously is anticonvulsant, and, NPY null mutant mice are more susceptible to kainate-induced seizures. In order to better understand the potential role of NPY in epileptogenesis, the present studies investigated the development of amygdala kindling, post-kindling seizure thresholds, and anticonvulsant effects of carbamazepine and levetiracetam in 129S6/SvEv NPY(+/+) and NPY(-/-) mice. In addition, susceptibility to pilocarpine- and kainate-induced seizures was compared in NPY(+/+) and (-/-) mice. The rate of amygdala kindling development did not differ in the NPY(-/-) and NPY(+/+) mice either when kindling stimuli were presented once daily for at least 20 days, or, 12 times daily for 2 days. However, during kindling development, the NPY(-/-) mice had higher seizure severity scores and longer afterdischarge durations than the NPY(+/+) mice. Post-kindling, the NPY(-/-) mice had markedly lower afterdischarge thresholds and longer afterdischarge durations than NPY (+/+) mice. Carbamazepine and levetiracetam increased the seizure thresholds of both NPY (-/-) and (+/+) mice. In addition, NPY (-/-) mice had lower thresholds for both kainate- and pilocarpine-induced seizures. The present results in amygdala kindling and chemical seizure models suggest that NPY may play a more prominent role in determining seizure thresholds and severity of seizures than in events leading to epileptogenesis. In addition, a lack of NPY does not appear to confer drug-resistance in that carbamazepine and levetiracetam were anticonvulsant in both wild type (WT) and NPY null mutant mice.

  7. Surveys about curative effect of anti-epilepsy medicine in the treatment of SUNCT%抗癫痫药治疗SUNCT综合征的效果观察

    Institute of Scientific and Technical Information of China (English)

    陈勇

    2014-01-01

    目的:验证抗癫痫药治疗SUNCT综合征的有效性。方法采用开放性自身对照研究,对比5例SUNCT综合征对卡马西平和加巴喷丁的治疗反应。结果卡马西平和加巴喷丁两种癫痫药均有效,加巴喷丁优于卡马西平。结论加巴喷丁可作为SUNCT综合征的一线治疗药物。%Objective To verify the curative effect of anti-epilepsy medicine in the treatment of short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Methods Comparing 5 cases of SUNCT’s therapeutic reaction with Carbamazepine and gabapentin though the method of self-control study. Results Both two anti-epilepsy medicines of carbamazepine and gabapentin were effective, however, gabapentin was better than carbamazepine. Conclusion The first choice medicine for the treatment of SUNCT is gabapentin.

  8. Ornamental plants for micropollutant removal in wetland systems.

    Science.gov (United States)

    Macci, Cristina; Peruzzi, Eleonora; Doni, Serena; Iannelli, Renato; Masciandaro, Grazia

    2015-02-01

    The objective of this paper was to evaluate the efficiency of micropollutant removal, such as Cu, Zn, carbamazepine, and linear alkylbenzene sulfonates (LAS), through the use of a subsurface vertical flow constructed wetland system with ornamental plants. Zantedeschia aethiopica, Canna indica, Carex hirta, Miscanthus sinensis, and Phragmites australis were selected and planted in lysimeters filled up with gravel. The lysimeters were completely saturated with synthetic wastewater (N 280 mg L(-1), P 30 mg L(-1), Cu 3.6 mg L(-1), Zn 9 mg L(-1), carbamazepine 5 μg L(-1), linear alkylbenzene sulfonates 14 mg L(-1)), and the leaching water was collected for analysis after 15, 30, and 60 days in winter-spring and spring-summer periods. Nutrients (N and P) and heavy metals decreased greatly due to both plant activity and adsorption. C. indica and P. australis showed the highest metal content in their tissues and also the greatest carbamazepine and LAS removal. In these plants, the adsorption/degradation processes led to particularly high oxidative stress, as evidenced by the significantly high levels of ascorbate peroxidase activity detected. Conversely, Z. aethiopica was the less efficient plant in metal and organic compound removal and was also less stressed in terms of ascorbate peroxidase activity.

  9. Impact of soil properties on selected pharmaceuticals adsorption in soils

    Science.gov (United States)

    Kodesova, Radka; Kocarek, Martin; Klement, Ales; Fer, Miroslav; Golovko, Oksana; Grabic, Roman; Jaksik, Ondrej

    2014-05-01

    The presence of human and veterinary pharmaceuticals in the environment has been recognized as a potential threat. Pharmaceuticals may contaminate soils and consequently surface and groundwater. Study was therefore focused on the evaluation of selected pharmaceuticals adsorption in soils, as one of the parameters, which are necessary to know when assessing contaminant transport in soils. The goals of this study were: (1) to select representative soils of the Czech Republic and to measure soil physical and chemical properties; (2) to measure adsorption isotherms of selected pharmaceuticals; (3) to evaluate impact of soil properties on pharmaceutical adsorptions and to propose pedotransfer rules for estimating adsorption coefficients from the measured soil properties. Batch sorption tests were performed for 6 selected pharmaceuticals (beta blockers Atenolol and Metoprolol, anticonvulsant Carbamazepin, and antibiotics Clarithromycin, Trimetoprim and Sulfamethoxazol) and 13 representative soils (soil samples from surface horizons of 11 different soil types and 2 substrates). The Freundlich equations were used to describe adsorption isotherms. The simple correlations between measured physical and chemical soil properties (soil particle density, soil texture, oxidable organic carbon content, CaCO3 content, pH_H2O, pH_KCl, exchangeable acidity, cation exchange capacity, hydrolytic acidity, basic cation saturation, sorption complex saturation, salinity), and the Freundlich adsorption coefficients were assessed using Pearson correlation coefficient. Then multiple-linear regressions were applied to predict the Freundlich adsorption coefficients from measured soil properties. The largest adsorption was measured for Clarithromycin (average value of 227.1) and decreased as follows: Trimetoprim (22.5), Metoprolol (9.0), Atenolol (6.6), Carbamazepin (2.7), Sulfamethoxazol (1.9). Absorption coefficients for Atenolol and Metoprolol closely correlated (R=0.85), and both were also

  10. Effect of oxidation and catalytic reduction of trace organic contaminants on their activated carbon adsorption.

    Science.gov (United States)

    Schoutteten, Klaas V K M; Hennebel, Tom; Dheere, Ellen; Bertelkamp, Cheryl; De Ridder, David J; Maes, Synthia; Chys, Michael; Van Hulle, Stijn W H; Vanden Bussche, Julie; Vanhaecke, Lynn; Verliefde, Arne R D

    2016-12-01

    The combination of ozonation and activated carbon (AC) adsorption is an established technology for removal of trace organic contaminants (TrOCs). In contrast to oxidation, reduction of TrOCs has recently gained attention as well, however less attention has gone to the combination of reduction with AC adsorption. In addition, no literature has compared the removal behavior of reduction vs. ozonation by-products by AC. In this study, the effect of pre-ozonation vs pre-catalytic reduction on the AC adsorption efficiency of five TrOCs and their by-products was compared. All compounds were susceptible to oxidation and reduction, however the catalytic reductive treatment proved to be a slower reaction than ozonation. New oxidation products were identified for dinoseb and new reduction products were identified for carbamazepine, bromoxynil and dinoseb. In terms of compatibility with AC adsorption, the influence of the oxidative and reductive pretreatments proved to be compound dependent. Oxidation products of bromoxynil and diatrizoic acid adsorbed better than their parent TrOCs, but oxidation products of atrazine, carbamazepine and dinoseb showed a decreased adsorption. The reductive pre-treatment showed an enhanced AC adsorption for dinoseb and a major enhancement for diatrizoic acid. For atrazine and bromoxynil, no clear influence on adsorption was noted, while for carbamazepine, the reductive pretreatment resulted in a decreased AC affinity. It may thus be concluded that when targeting mixtures of TrOCs, a trade-off will undoubtedly have to be made towards overall reactivity and removal of the different constituents, since no single treatment proves to be superior to the other.

  11. Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring.

    Science.gov (United States)

    Shibata, Mai; Hashi, Sachiyo; Nakanishi, Haruka; Masuda, Satohiro; Katsura, Toshiya; Yano, Ikuko

    2012-12-01

    The purpose of this study was to develop an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics for routine therapeutic monitoring. The antiepileptics used in the analyses were carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam, clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide. After protein precipitation of 50 μL plasma with methanol, the supernatant was diluted with water or was evaporated to dryness and reconstituted with mobile phase in the case of benzodiazepines. Separation was achieved on an Acquity UPLC BEH C₁₈ column with a gradient mobile phase of 10 mm ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.4 mL/min. An Acquity TQD instrument in multiple reaction monitoring mode with ion mode switching was used for detection. All antiepileptics were detected and quantified within 10 min, with no endogenous interference. All the calibration curves showed good linearity in the therapeutic range (r²  < 0.99). The precision and accuracy values for intra- and inter-assays were within ±15% except for phenobarbital and tiagabine. A good correlation was observed between the concentration of clinical samples measured by the new method described here and the conventional methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than those detected by the immunoassays, which might be caused by the cross-reaction of antibodies with their metabolites. In conclusion, we developed a simple and selective UPLC-MS/MS method suitable for routine therapeutic monitoring of antiepileptics.

  12. In-stream attenuation of neuro-active pharmaceuticals and their metabolites

    Science.gov (United States)

    Writer, Jeffrey; Antweiler, Ronald C.; Ferrar, Imma; Ryan, Joseph N.; Thurman, Michael

    2013-01-01

    In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

  13. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.

    Science.gov (United States)

    Jo, Sooyeon; Bean, Bruce P

    2017-04-01

    Lacosamide is an antiseizure agent that targets voltage-dependent sodium channels. Previous experiments have suggested that lacosamide is unusual in binding selectively to the slow-inactivated state of sodium channels, in contrast to drugs like carbamazepine and phenytoin, which bind tightly to fast-inactivated states. Using heterologously expressed human Nav1.7 sodium channels, we examined the state-dependent effects of lacosamide. Lacosamide induced a reversible shift in the voltage dependence of fast inactivation studied with 100-millisecond prepulses, suggesting binding to fast-inactivated states. Using steady holding potentials, lacosamide block was very weak at -120 mV (3% inhibition by 100 µM lacosamide) but greatly enhanced at -80 mV (43% inhibition by 100 µM lacosamide), where there is partial fast inactivation but little or no slow inactivation. During long depolarizations, lacosamide slowly (over seconds) put channels into states that recovered availability slowly (hundreds of milliseconds) at -120 mV. This resembles enhancement of slow inactivation, but the effect was much more pronounced at -40 mV, where fast inactivation is complete, but slow inactivation is not, than at 0 mV, where slow inactivation is maximal, more consistent with slow binding to fast-inactivated states than selective binding to slow-inactivated states. Furthermore, inhibition by lacosamide was greatly reduced by pretreatment with 300 µM lidocaine or 300 µM carbamazepine, suggesting that lacosamide, lidocaine, and carbamazepine all bind to the same site. The results suggest that lacosamide binds to fast-inactivated states in a manner similar to other antiseizure agents but with slower kinetics of binding and unbinding.

  14. Emerging pollutants in the Esmeraldas watershed in Ecuador: discharge and attenuation of emerging organic pollutants along the San Pedro-Guayllabamba-Esmeraldas rivers.

    Science.gov (United States)

    Voloshenko-Rossin, A; Gasser, G; Cohen, K; Gun, J; Cumbal-Flores, L; Parra-Morales, W; Sarabia, F; Ojeda, F; Lev, O

    2015-01-01

    Water quality characteristics and emerging organic pollutants were sampled along the San Pedro-Guayllabamba-Esmeraldas River and its main water pollution streams in the summer of 2013. The annual flow rate of the stream is 22 000 Mm(3) y(-1) and it collects the wastewater of Quito-Ecuador in the Andes and supplies drinking water to the city of Esmeraldas near the Pacific Ocean. The most persistent emerging pollutants were carbamazepine and acesulfame, which were found to be stable along the San Pedro-Guayllabamba-Esmeraldas River, whereas the concentration of most other organic emerging pollutants, such as caffeine, sulfamethoxazole, venlafaxine, O-desmethylvenlafaxine, and steroidal estrogens, was degraded to a large extent along the 300 km flow. The mass rate of the sum of cocaine and benzoylecgonine, its metabolite, was increased along the stream, which may be attributed to coca plantations and wild coca trees. This raises the possibility of using river monitoring as an indirect way to learn about changes in coca plantations in their watersheds. Several organic emerging pollutants, such as venlafaxine, carbamazepine, sulphamethoxazole, and benzoylecgonine, survived even the filtration treatment at the Esmeraldas drinking water system, though all except for benzoylecgonine are found below 20 ng L(-1), and are therefore not likely to cause adverse health effects. The research provides a way to compare drug consumption in a major Latin American city (Quito) and shows that the consumption of most sampled drugs (carbamazepine, venlafaxine, O-desmethylvenlafaxine, sulphamethoxazole, ethinylestradiol) was below their average consumption level in Europe, Israel, and North America.

  15. Low removal of acidic and hydrophilic pharmaceutical products by various types of municipal wastewater treatment plants

    Directory of Open Access Journals (Sweden)

    Christian Gagnon

    2012-03-01

    Full Text Available Pharmaceutical substances represent a risk for aquatic environments and their potential impacts on the receiving environment are poorly understood. Municipal effluents are important sources of contaminants including common pharmaceuticals like anti-inflammatory and anti-convulsive substances. The removal of pharmaceuticals, particularly those highly soluble can represent a great challenge to conventional wastewater treatment processes. Hydrophilic drugs (e.g. acidic drugs have properties that can highly influence removal efficiencies of treatment plants. The performance of different wastewater treatment processes for the removal of specific pharmaceutical products that are expected to be poorly removed was investigated. The obtained results were compared to inherent properties of the studied substances. Clofibric acid, carbamazepine, diclofenac, ibuprofen and naproxen were largely found in physicochemical primary-treated effluents at concentrations ranging from 77 to 2384 ng/L. This treatment type showed removal yields lower than 30%. On the other hand, biological treatments with activated sludge under aerobic conditions resulted in much better removal rates (>50% for 5 of the 8 studied substances. Interestingly, this latter type of process showed evidence of selectivity with respect to the size (R2=0.7388, solubility (R2=0.6812, and partitioning (R2=0.9999 of the removed substances; the smallest and least sorbed substances seemed to be removed at better rates, while the persistent carbamazepine (392 ng/L and diclofenac (66 ng/L were poorly removed (<10% after biological treatment. In the case of treatment by aerated lagoons, the most abundant substances were the highly soluble hydroxy-ibuprofen (350-3321 ng/L, followed by naproxen (42-413 n/L and carbamazepine (254-386 ng/L. In order to assess the impacts of all these contaminants of various properties on the environment and human health, we need to better understand the chemical and physical

  16. Role of wetland organic matters as photosensitizer for degradation of micropollutants and metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunkyung [Department of Civil and Environmental Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Shon, Ho Kyong [School of Civil and Environmental Engineering, University of Technology, Sydney (UTS), PO Box 123, Broadway, Sydney 2007, NSW (Australia); Cho, Jaeweon, E-mail: chojw@yonsei.ac.kr [Department of Civil and Environmental Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749 (Korea, Republic of)

    2014-07-15

    Highlights: • Photodegradation of PPCPs was investigated in various NOM enriched solutions. • Direct and indirect photolysis experiments were conducted upon UV irradiation. • PPCPs showed different levels of photodegradation rates depending on their photoreactivity. • Allochthonous NOM inhibited the photolysis of target PPCPs. • Wetland NOM enhanced photodegradation of some conservative PPCPs. - Abstract: Overall photodegradation of pharmaceuticals, personal care products (PPCPs) and pharmaceutical metabolites were investigated in order to evaluate their photochemical fate in aquatic environments in various natural organic matter (NOM) enriched solutions. Tested PPCPs exhibited different rates of loss during direct and indirect photolysis. Here, only ultraviolet (UV) light source was used for direct photolysis and UV together with {sup 3}DOM{sup *}for indirect photolysis. Diclofenac and sulfamethoxazole were susceptible to photodegradation, whereas carbamazepine, caffeine, paraxanthine and tri(2-chloroethyl) phosphate (TCEP) showed low levels of photodegradation rate, reflecting their conservative photoreactivity. During indirect photodegradation, in contrast to the hydrophilic autochthonous NOM, allochthonous NOM with relatively high molecular weight (MW), specific ultraviolet absorbance (SUVA) and hydrophobicity (e.g., Suwannee River humic acid (SRHA)) revealed to significantly inhibit the photolysis of target micropollutants. The presence of Typha wetland NOM enhanced the indirect photolysis of well-known conservative micopollutants (carbamazepine and paraxanthine). And atenolol, carbamazepine, glimepiride, and N-acetyl-sulfamethoxazole were found to be sensitive to the triplet excited state of dissolved organic matter ({sup 3}DOM{sup *}) with Typha wetland NOM under deoxygenated condition. This suggests that photolysis in constructed wetlands connected to the wastewater treatment plant can enhance the degradation of some anthropogenic micropollutants

  17. On-line solid-phase extraction coupled with high-performance liquid chromatography and tandem mass spectrometry (SPE-HPLC-MS-MS) for quantification of bromazepam in human plasma: an automated method for bioequivalence studies.

    Science.gov (United States)

    Gonçalves, José Carlos Saraiva; Monteiro, Tânia Maria; Neves, Claúdia Silvana de Miranda; Gram, Karla Regina da Silva; Volpato, Nádia Maria; Silva, Vivian A; Caminha, Ricardo; Gonçalves, Maria do Rocio Bencke; Santos, Fábio Monteiro Dos; Silveira, Gabriel Estolano da; Noël, François

    2005-10-01

    A validated method for on-line solid-phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry (SPE-HPLC-MS-MS) is described for the quantification of bromazepam in human plasma. The method involves a dilution of 300 muL of plasma with 100 muL of carbamazepine (2.5 ng/mL), used as internal standard, vortex-mixing, centrifugation, and injection of 100 muL of the supernate. The analytes were ionized using positive electrospray mass spectrometry then detected by multiple reaction monitoring (MRM). The m/z transitions 316-->182 (bromazepam) and 237-->194 (carbamazepine) were used for quantification. The calibration curve was linear from 1 ng/mL (limit of quantification) to 200 ng/mL. The retention times of bromazepam and carbamazepine were 2.6 and 3.2 minutes, respectively. The intraday and interday precisions were 3.43%-15.45% and 5.2%-17%, respectively. The intraday and interday accuracy was 94.00%-103.94%. This new automated method has been successfully applied in a bioequivalence study of 2 tablet formulations of 6 mg bromazepam: Lexotan(R) from Produtos Roche Químicos e Farmacêuticos SA, Rio de Janeiro, Brazil (reference) and test formulation from Laboratórios Biosintética Ltda, São Paulo, Brazil. Because the 90% CI of geometric mean ratios between reference and test were completely included in the 80%-125% interval, the 2 formulations were considered bioequivalent. The comparison of different experimental conditions for establishing a dissolution profile in vitro along with our bioavailability data further allowed us to propose rationally based experimental conditions for a dissolution test of bromazepam tablets, actually lacking a pharmacopeial monograph.

  18. Sorption and degradation of selected pharmaceuticals in representative soils of the Czech Republic

    Science.gov (United States)

    Kodesova, Radka; Kocarek, Martin; Klement, Ales; Golovko, Oksana; Grabic, Roman; Fer, Miroslav; Nikodem, Antonin; Jaksik, Ondrej

    2015-04-01

    Knowledge of contaminant behavior (e.g. its sorption onto soil particle, degradation etc.) is essential when assessing contaminant migration in soil and groundwater environment. This study was focused on evaluating sorption isotherms and half-lives for 7 pharmaceuticals (clarithromycin, trimethoprim, metoprolol, atenolol, clindamycin, carbamazepine, sulfamethoxazole) on 13 soils of different soil properties. Sorption of ionizable compounds was highly affected by soil pH. The sorption coefficient of sulfamethoxazole was negatively correlated to soil pH and thus positively related to hydrolytic acidity and exchangeable acidity. Sorption coefficients for clindamycin and clarithromycin were positively related to soil pH and thus negatively related to hydrolytic acidity and exchangeable acidity and positively related to base cation saturation. Sorption coefficients for the remaining pharmaceuticals (trimethoprim, metoprolol, atenolol, and carbamazepine) were also positively correlated with the base cation saturation and cation exchange capacity. Degradation rates in some degree reflected sorption of studied pharmaceuticals on soil particles and increased with decreasing sorption. The highest mobility in studied soils was observed for sulfamethoxazole, but this pharmaceutical was relatively quickly degraded. The second highest mobility was found for carbamazepine, which mostly did not noticeably degrade during our experiments. Thus this pharmaceutical has the highest potential to migrate in water environment. The lowest mobility was observed for clarithromycin. However, this pharmaceutical due to its stability may be retained in an environment for a long time. Acknowledgement: The authors acknowledge the financial support of the Czech Science Foundation (Project No. 13-12477S, Transport of pharmaceuticals in soils). References: Kodesova, R., Grabic, R., Kocarek, M., Klement, A., Golovko, O., Fer, M., Nikodem, A., Jaksik, O., Pharmaceuticals' sorptions relative to

  19. Human leukocyte antigen (HLA) pharmacogenomic tests: potential and pitfalls.

    Science.gov (United States)

    Daly, Ann K

    2014-02-01

    Adverse drug reactions involving a range of prescribed drugs and affecting the skin, liver and other organs show strong associations with particular HLA alleles. For some reactions, HLA typing prior to prescription, so that those positive for the risk allele are not given the drug associated with the reaction, shows high positive and negative predictive values. The best example of clinical implementation relates to the hypersensitivity reaction induced by the anti-HIV drug abacavir. When this reaction is phenotyped accurately, 100% of those who develop it are positive for HLA-B*57:01. Drug regulators worldwide now recommend genotyping for HLA-B*57:01 before abacavir is prescribed. Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrosis can be induced by carbamazepine and other anticonvulsant drugs. In certain East Asians, these reactions are significantly associated with HLA-B*15:02, and typing for this allele is now recommended prior to carbamazepine prescription in these populations. Other HLA associations have been described for skin rash induced by carbamazepine, allopurinol and nevirapine and for liver injury induced by flucloxacillin, amoxicillin-clavulanate, lapatanib, lumiracoxib and ticlopidine. However, the predictive values for typing HLA alleles associated with these adverse reactions are lower. Clinical implementation therefore seems unlikely. Performing HLA typing is relatively complex compared with genotyping assays for single nucleotide polymorphisms. With emphasis on HLA-B*57:01, the approaches used commonly, including use of sequence-specific oligonucleotide PCR primers and DNA sequencing are considered, together with their successful implementation. Genotyping single nucleotide polymorphisms tagging HLA alleles is a simpler alternative to HLA typing but appears insufficiently accurate for clinical use.

  20. Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China.

    Science.gov (United States)

    Cai, Mei-Quan; Wang, Rong; Feng, Li; Zhang, Li-Qiu

    2015-02-01

    A simultaneous determination method of 14 multi-class pharmaceuticals using solid-phase extraction (SPE) followed by high-performance liquid chromatography-tandem mass spectrometer (HPLC-MS/MS) was established to measure the occurrence and distribution of these pharmaceuticals in tap water and a drinking water treatment plant (DWTP) in Beijing, China. Target compounds included seven anti-inflammatory drugs, two antibacterial drugs, two lipid regulation drugs, one antiepileptic drug, and one hormone. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 0.01 to 1.80 ng/L and 0.05 to 3.00 ng/L, respectively. Intraday and inter-day precisions, recoveries of different matrices, and matrix effects were also investigated. Of the 14 pharmaceutical compounds selected, nine were identified in tap water of Beijing downtown with the concentration up to 38.24 ng/L (carbamazepine), and the concentration levels of detected pharmaceuticals in tap water (water and finished water at the concentration ranged from 0.10 to 16.23 and 0.13 to 17.17 ng/L, respectively. Five compounds were detected most frequently in DWTP, namely antipyrine, carbamazepine, isopropylantipyrine, aminopyrine, and bezafibrate. Ibuprofen was found to be the highest concentration pharmaceutical during DWTP, up to 53.30 ng/L. DWTP shows a positive effect on the removal of most pharmaceuticals with 81.2-99.5 % removal efficiencies, followed by carbamazepine with 55.4 % removal efficiency, but it has no effect for removing ibuprofen and bezafibrate.

  1. Pharmaceuticals' sorptions relative to properties of thirteen different soils.

    Science.gov (United States)

    Kodešová, Radka; Grabic, Roman; Kočárek, Martin; Klement, Aleš; Golovko, Oksana; Fér, Miroslav; Nikodem, Antonín; Jakšík, Ondřej

    2015-04-01

    Transport of human and veterinary pharmaceuticals in soils and consequent ground-water contamination are influenced by many factors, including compound sorption on soil particles. Here we evaluate the sorption isotherms for 7 pharmaceuticals on 13 soils, described by Freundlich equations, and assess the impact of soil properties on various pharmaceuticals' sorption on soils. Sorption of ionizable pharmaceuticals was, in many cases, highly affected by soil pH. The sorption coefficient of sulfamethoxazole was negatively correlated to soil pH, and thus positively related to hydrolytic acidity and exchangeable acidity. Sorption coefficients for clindamycin and clarithromycin were positively related to soil pH and thus negatively related to hydrolytic acidity and exchangeable acidity, and positively related to base cation saturation. The sorption coefficients for the remaining pharmaceuticals (trimethoprim, metoprolol, atenolol, and carbamazepine) were also positively correlated with the base cation saturation and cation exchange capacity. Positive correlations between sorption coefficients and clay content were found for clindamycin, clarithromycin, atenolol, and metoprolol. Positive correlations between sorption coefficients and organic carbon content were obtained for trimethoprim and carbamazepine. Pedotransfer rules for predicting sorption coefficients of various pharmaceuticals included hydrolytic acidity (sulfamethoxazole), organic carbon content (trimethoprimand carbamazepine), base cation saturation (atenolol and metoprolol), exchangeable acidity and clay content (clindamycin), and soil active pH and clay content (clarithromycin). Pedotransfer rules, predicting the Freundlich sorption coefficients, could be applied for prediction of pharmaceutical mobility in soils with similar soil properties. Predicted sorption coefficients together with pharmaceutical half-lives and other imputes (e.g., soil-hydraulic, geological, hydro-geological, climatic) may be used for

  2. Influence of Ivabradine on the Anticonvulsant Action of Four Classical Antiepileptic Drugs Against Maximal Electroshock-Induced Seizures in Mice.

    Science.gov (United States)

    Sawicka, Katarzyna M; Wawryniuk, Agnieszka; Zwolak, Agnieszka; Daniluk, Jadwiga; Szpringer, Monika; Florek-Luszczki, Magdalena; Drop, Bartlomiej; Zolkowska, Dorota; Luszczki, Jarogniew J

    2017-04-01

    Although the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in neuronal excitability and synaptic transmission is still unclear, it is postulated that the HCN channels may be involved in seizure activity. The aim of this study was to assess the effects of ivabradine (an HCN channel inhibitor) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Tonic seizures (maximal electroconvulsions) were evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combinations of ivabradine with classical antiepileptic drugs were measured in mice along with total brain antiepileptic drug concentrations. Results indicate that ivabradine (10 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of valproate and considerably reduced that of phenytoin in the mouse maximal electroshock-induced seizure model. Ivabradine (10 mg/kg) had no impact on the anticonvulsant potency of carbamazepine and phenobarbital in the maximal electroshock-induced seizure test in mice. Ivabradine (10 mg/kg) significantly diminished total brain concentration of phenytoin and had no effect on total brain valproate concentration in mice. In conclusion, the enhanced anticonvulsant action of valproate by ivabradine in the mouse maximal electroshock-induced seizure model was pharmacodynamic in nature. A special attention is required when combining ivabradine with phenytoin due to a pharmacokinetic interaction and reduction of the anticonvulsant action of phenytoin in mice. The combinations of ivabradine with carbamazepine and phenobarbital were neutral from a preclinical viewpoint.

  3. Complex visual hallucinations in a Parkinson patient: don't blame James if it's Charles's fault.

    Science.gov (United States)

    Segers, Kurt

    2013-03-01

    A patient with a history of Parkinson's disease and severe bilateral peripheral vision loss due to vitreous hemorrhages had complex visual hallucinations that persisted for three days and appeared every morning on awakening. The persistent nature of these hallucinations, the patient's preserved insight, and the presence of severe visual impairment was suggestive for Charles Bonnet syndrome rather than Parkinson-related hallucinations. A treatment with carbamazepine was started and proved to be successful. Physicians treating Parkinson patients should be familiar with Charles Bonnet syndrome and consider it as a potential alternative etiology for visual hallucinations, especially when the patient has severely impaired vision and when the hallucinations are sustained during wakefulness.

  4. Degradation of PPCPs in activated sludge from different WWTPs in Denmark

    DEFF Research Database (Denmark)

    Chen, Xijuan; Vollertsen, Jes; Nielsen, Jeppe Lund

    2015-01-01

    was performed to assess the removal of frequently occurring pharmaceuticals (Naproxen, Fenoprofen, Ketoprofen, Dichlofenac, Carbamazepine) and the biocide Triclosan in activated sludge from four different Danish WWTPs. The respective degradation constants were compared to operational parameters previous shown...... to be of importance for degradation of micropollutants such as biomass concentration, and sludge retention time (SRT). The most rapid degradation, was observed for NSAID pharmaceuticals (55–90 % for Fenoprofen, 77–94 % for Ketoprofen and 46–90 % for Naproxen), followed by Triclosan (61–91 %), while Dichlofenac...

  5. Thirty-Two Cases of Trigeminal Neuralgia Treated with Acupuncture plus Chinese Traditional Drugs

    Institute of Scientific and Technical Information of China (English)

    Zheng Xiangmei; Suo Yunxi; Chen Zhengqiu

    2006-01-01

    @@ Trigeminal neuralgia refers to the kind of pain occurring in the distribution areas of the trigeminal nerves. The pain attacking periodically is so intense like either knife-cutting or electric stroke. However,no abnormality is found in the patients when the attack ceases. By means of acupuncture plus Chinese traditional drugs, the authors had treated 32cases of the disease from March of 1999 to March of 2003, and its effect is compared with that of carbamazepine in 29 cases. A report follows.

  6. Abnormal sexual behavior during sleep in temporal lobe epilepsy: a case report.

    Science.gov (United States)

    Pelin, Zerrin; Yazla, Ece

    2012-06-01

    Herein, we describe a case who presented with abnormal sexual behaviour during sleep. Video-electroencephalography monitoring during sleep revealed an abnormality suggesting an epileptic basis. The patient was successfully treated with carbamazepin. The psychiatric symptoms that were thought to be related to abnormal sexual behaviours were controlled with antipsychotic treatment. Our findings strongly emphasize the fact that efforts should be spent to increase awareness of seizure activity at night, which can be misinterpreted as benign parasomnias. Such a misinterpretation may have serious consequences, such as insufficient seizure control, progressive personality changes, and cognitive impairment.

  7. The role of topiramate and other anticonvulsants in the treatment of alcohol dependence: a clinical review.

    Science.gov (United States)

    De Sousa, Avinash

    2010-03-01

    Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyzed, along with its proposed mechanism of action in alcohol dependence. A review of data available on other anticonvulsants like carbamazepine, oxcarbazepine, sodium valproate, gabapentin and levetiracetam are presented and their potential in the treatment of alcohol dependence is considered, together with future research directions.

  8. Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters

    Science.gov (United States)

    Writer, Jeffrey; Ferrer, Imma; Barber, Larry B.; Thurman, E. Michael

    2013-01-01

    Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations ± standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700 ± 1000 ng L−1, 2100 ± 1700 ng L−1, carbamazepine and 10-hydroxy-carbamazepine 480 ± 380 ng L−1, 360 ± 400 ng L−1, venlafaxine and O-desmethyl-venlafaxine 1400 ± 1300 ng L−1, 1800 ± 2300 ng L−1. Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that

  9. Pharmacologic treatment of pain in polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Jensen, Troels Staehelin

    2000-01-01

    channel blocker gabapentin, and 3.4 for the mixed opioid and monoaminergic drug tramadol, as calculated from a sufficiently large number of patients. Favorable point estimates of NNT of 1.9 for the NMDA-antagonist dextromethorphan and 3.4 for L-dopa were determined from a limited number of data....... Tricyclic antidepressants are at the moment still the drugs of first choice, and drugs such as gabapentin, carbamazepine, and tramadol may be tried if contraindications or tolerability problems are encountered with the tricyclics....

  10. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy

    OpenAIRE

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-01-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone an...

  11. Evaluation of regional cerebral blood flow in a patient with musical hallucinations.

    Science.gov (United States)

    Shoyama, Masaru; Ukai, Satoshi; Kitabata, Yuji; Yamamoto, Masahiro; Okumura, Masatoshi; Kose, Asami; Tsuji, Tomikimi; Shinosaki, Kazuhiro

    2010-02-01

    A 52-year-old woman with musical hallucinations was examined using brain single photon emission computed tomography (SPECT) with 99mTc-ECD. Changes in regional cerebral blood flow (rCBF) after carbamazepine treatment were assessed using a three-dimensional stereotaxic ROI template. Following treatment, rCBF was decreased in the subcortical structures and increased in the global cortical regions. From our findings, we propose that rCBF values in subcortical structures represent abnormalities similar to those reported in previous reports or other psychiatric disorders, while those in cortical regions suggest background brain dysfunctions that result in generation of musical hallucinations.

  12. Determinação simultânea de carbamazepina, fenitoína e fenobarbital em sangue seco em papel por cromatografia líquida de alta eficiência

    OpenAIRE

    Gabriela Martins Silva de Lima; Roberta Zilles Hahn; Cristina Rama; Liliane Rhoden; Paulina Hidalgo; Cleber Álvares da Silva; Marina Venzon Antunes; Rafael Linden

    2014-01-01

    Carbamazepine, phenobarbital and phenytoin were determined in dried blood spots (DBS) by high performance liquid chromatography, after extraction of 8 mm DBS using a mixture of acetonitrile and methanol. Analytes were separated by reversed-phase chromatography, with a run time of 17 minutes. Intra-assay and inter-assay precisions were in the 5.3 to 8.4% and 3.3 to 5.2% ranges, respectively. Accuracy was in the 98.8 to 104.3% range. The method had sensitivity to detect all analytes at levels b...

  13. Determinação simultânea de topiramato, carbamazepina, fenitoína e fenobarbital em plasma empregando cromatografia a gás com detector de nitrogênio e fósforo

    OpenAIRE

    Roberta Zilles Hahn; Olyr Celestino Kreutz; Marina Venzon Antunes; Rafael Linden; Juliana da Silva; Cléber Álvares da Silva

    2013-01-01

    Topiramate and the other frequently co-administered antiepileptic drugs carbamazepine, phenytoin and phenobarbital were determined in 100 µL plasma samples by gas chromatography with nitrogen phosphorus detection (GC-NPD), after a one-step liquid-liquid extraction with ethyl acetate, followed by flash methylation with trimethylphenylammonium hydroxide. Total chromatographic run time was 12.5 min. Intra-assay and inter-assay precision was 2.5-7.3% and 1.6-5.2%, respectively. Accuracy was 100.1...

  14. [Haematological adverse effects caused by psychiatric drugs].

    Science.gov (United States)

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned.

  15. Paroxysmal dysarthria and ataxia in multiple sclerosis and corresponding magnetic resonance imaging findings.

    Science.gov (United States)

    Li, Yongmei; Zeng, Chun; Luo, Tianyou

    2011-02-01

    Paroxysmal dysarthria (PD) and paroxysmal dysarthria-ataxia (PDA) syndromes are uncommon symptoms of the neurological dysfunction in multiple sclerosis (MS). We describe two patients who had clinically definite MS presented with symptomatic PD and PDA syndromes, respectively, related to demyelinating lesions. In one patient, the PD symptom was the initial manifestation of an acute episode. In the other patient, the episode of dysarthria was accompanied by ataxia disorders. Both patients had midbrain lesions at or below the level of the right red nucleus on magnetic resonance imaging (MRI), confirming that this area is critically involved. Both responded well to carbamazepine (CBZ).

  16. Development of an in vitro assay for the investigation of metabolism-induced drug hepatotoxicity

    DEFF Research Database (Denmark)

    Otto, Marie; Hansen, Steen Honore'; Dalgaard, L.

    2008-01-01

    the cytotoxicity of diclofenac was increased by S9 enzymes when an NADPH regenerating system was used. The increased toxicity was NADPH dependent. Reactive drug metabolites of diclofenac, formed by NADPH-dependent metabolism, were identified by LC-MS. Furthermore, an increase in toxicity, not related to enzymatic...... activity but to G6P, was observed for diclofenac and minocycline. Tacrine and amodiaquine displayed decreased toxicity with S9-mix, and carbamazepine, phenytoin, bromfenac and troglitazone were nontoxic at all tested concentrations, with or without S9-mix. The results show that this method...

  17. Continuous-flow photocatalytic treatment of pharmaceutical micropollutants: Activity, inhibition, and deactivation of TiO2 photocatalysts in wastewater effluent

    KAUST Repository

    Carbonaro, Sean

    2013-01-01

    Titanium dioxide (TiO2) photocatalysts have been shown to be effective at degrading a wide range of organic micropollutants during short-term batch experiments conducted under ideal laboratory solution conditions (e.g., deionized water). However, little research has been performed regarding longer-term photocatalyst performance in more complex matrices representative of contaminated water sources (e.g., wastewater effluent, groundwater). Here, a benchtop continuous-flow reactor was developed for the purpose of studying the activity, inhibition, and deactivation of immobilized TiO2 photocatalysts during water treatment applications. As a demonstration, degradation of four pharmaceutical micropollutants (iopromide, acetaminophen, sulfamethoxazole, and carbamazepine) was monitored in both a pH-buffered electrolyte solution and a biologically treated wastewater effluent (WWE) to study the effects of non-target constituents enriched in the latter matrix. Reactor performance was shown to be stable over 7d when treating micropollutants in buffered electrolyte, with 7-d averaged kobs values (acetaminophen=0.97±0.10h-1; carbamazepine=0.50±0.04h-1; iopromide=0.49±0.03h-1; sulfamethoxazole=0.79±0.06h-1) agreeing closely with measurements from short-term circulating batch reactions. When reactor influent was switched to WWE, treatment efficiencies decreased to varying degrees (acetaminophen=40% decrease; carbamazepine=60%; iopromide=78%; sulfamethoxazole=54%). A large fraction of the catalyst activity was recovered upon switching back to the buffered electrolyte influent after 4d, suggesting that much of the observed decrease resulted from reversible inhibition by non-target constituents (e.g., scavenging of photocatalyst-generated OH). However, there was also a portion of the decrease in activity that was not recovered, indicating WWE constituents also contributed to photocatalyst deactivation (acetaminophen=6% deactivation; carbamazepine=24%; iopromide=16

  18. Behaviour of pharmaceuticals and psychotic drugs in conventional and advanced wastewater treatments; Comportamiento de medicamentos y psicofarmacos en tratamaientos de depuracion convencionales y terciarios

    Energy Technology Data Exchange (ETDEWEB)

    Cortacans Torre, J. A.; Castillo Gonzalez, I. del; Hernandez Lehmann, A.; Hernandez Munoz, A.; Rodriguez Barrera, X.

    2009-07-01

    The occurrence of various pharmaceuticals and psychotic drugs in wastewater and their removal rates in a conventional wastewater treatment plant has been investigated. The psychoactive drugs are poorly removed in the biological step. However, most pharmaceuticals except of carbamazepine, are significantly biodegraded depending the removal degree on the type of compound and on the sludge retention time of the biological treatment. Also, the removal efficiency of conventional tertiary treatments and ultrafiltration and nano filtration membranes using two pilot plants was examined. the effects of retaining pharmaceuticals with ultrafiltration and nano filtration membranes do not greatly differ despite the difference in their pore size. (Author) 25 refs.

  19. A case of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) related to rufinamide.

    Science.gov (United States)

    Shahbaz, S; Sivamani, R K; Konia, T; Burrall, B

    2013-04-15

    Drug Rash (or Reaction) with Eosinophilia and Systemic Symptoms (DRESS) is a potentially life-threatening hypersensitivity reaction to drugs characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and involvement of internal organs. Initially coined in 1996, the term is used to refer to an idiosyncratic reaction to several drugs, the most common of which are carbamazepine, allopurinol, sulfasalazine, and phenobarbital. We report the first case of DRESS related to rufinamide in a ten year old boy with a history of a complex seizure disorder.

  20. Analysis of psychoactive substances in water by information dependent acquisition on a hybrid quadrupole time-of-flight mass spectrometer.

    Science.gov (United States)

    Andrés-Costa, María Jesús; Andreu, Vicente; Picó, Yolanda

    2016-08-26

    Emerging drugs of abuse, belonging to many different chemical classes, are attracting users with promises of "legal" highs and easy access via internet. Prevalence of their consumption and abuse through wastewater-based epidemiology can only be realized if a suitable analytical screening procedure exists to detect and quantify them in water. Solid-phase extraction and ultra-high performance liquid chromatography quadrupole time-of-flight-mass spectrometry (UHPLC-QqTOF-MS/MS) was applied for rapid suspect screening as well as for the quantitative determination of 42 illicit drugs and metabolites in water. Using this platform, we were able to identify amphetamines, tryptamines, piperazines, pyrrolidinophenones, arylcyclohexylamines, cocainics, opioids and cannabinoids. Additionally, paracetamol, carbamazepine, ibersartan, valsartan, sulfamethoxazole, terbumeton, diuron, etc. (including degradation products as 3-hydroxy carbamazepine or deethylterbuthylazine) were detected. This method encompasses easy sample preparation and rapid identification of psychoactive drugs against a database that cover more than 2000 compounds that ionized in positive mode, and possibility to identify metabolites and degradation products as well as unknown compounds. The method for river water, influent and effluents samples was fully validated for the target psychoactive substances including assessment of matrix effects (-88-67.8%), recovery (42-115%), precision (psychoactive drugs biomarkers and other water contaminants is demonstrated.

  1. Impact of humic acid fouling on membrane performance and transport of pharmaceutically active compounds in forward osmosis.

    Science.gov (United States)

    Xie, Ming; Nghiem, Long D; Price, William E; Elimelech, Menachem

    2013-09-01

    The impact of humic acid fouling on the membrane transport of two pharmaceutically active compounds (PhACs) - namely carbamazepine and sulfamethoxazole - in forward osmosis (FO) was investigated. Deposition of humic acid onto the membrane surface was promoted by the complexation with calcium ions in the feed solution and the increase in ionic strength at the membrane surface due to the reverse transport of NaCl draw solute. The increase in the humic acid deposition on the membrane surface led to a substantial decrease in the membrane salt (NaCl) permeability coefficient but did not result in a significant decrease in the membrane pure water permeability coefficient. As the deposition of humic acid increased, the permeation of carbamazepine and sulfamethoxazole decreased, which correlated well with the decrease in the membrane salt (NaCl) permeability coefficient. It is hypothesized that the hydrated humic acid fouling layer hindered solute diffusion through the membrane pore and enhanced solute rejection by steric hindrance, but not the permeation of water molecules. The membrane water and salt (NaCl) permeability coefficients were fully restored by physical cleaning of the membrane, suggesting that humic acid did not penetrate into the membrane pores.

  2. Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15

    Energy Technology Data Exchange (ETDEWEB)

    Bui, Tung Xuan, E-mail: bxtung@gist.ac.kr [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of); Choi, Heechul, E-mail: hcchoi@gist.ac.kr [Department of Environmental Science and Engineering, Gwangju Institute of Science and Technology (GIST), 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of)

    2009-09-15

    The removal of five selected pharmaceuticals, viz., carbamazepine, clofibric acid, diclofenac, ibuprofen, and ketoprofen was examined by batch sorption experiments onto a synthesized mesoporous silica SBA-15. SBA-15 was synthesized and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N{sub 2} adsorption-desorption measurement, and point of zero charge (PZC) measurement. Pharmaceutical adsorption kinetics was rapid and occurred on a scale of minutes, following a pseudo-second-order rate expression. Adsorption isotherms were best fitted by the Freundlich isotherm model. High removal rates of individual pharmaceuticals were achieved in acidic media (pH 3-5) and reached 85.2% for carbamazepine, 88.3% for diclofenac, 93.0% for ibuprofen, 94.3% for ketoprofen, and 49.0% for clofibric acid at pH 3 but decreased with increase in pH. SBA-15 also showed high efficiency for removal of a mixture of 5 pharmaceuticals. Except for clofibric acid (35.6%), the removal of pharmaceuticals in the mixture ranged from 75.2 to 89.3%. Based on adsorption and desorption results, the mechanism of the selected pharmaceuticals was found to be a hydrophilic interaction, providing valuable information for further studies to design materials for the purpose. The results of this study suggest that mesoporous-silica-based materials are promising adsorbents for removing pharmaceuticals from not only surface water but also wastewater of pharmaceutical industrial manufactures.

  3. OBSERVATION OF THERAPEUTIC EFFECT ON TREATMENT OF THE GREATER OCCIPITAL NEURALGIA WITH ACUPUNCTURE

    Institute of Scientific and Technical Information of China (English)

    LIU Xue-qi; LIU Wei

    2006-01-01

    Objective: To compare the differences in therapeutic effects on treatments of the greater occipital neuralgia between acupuncture and western medicine. Method: Sixty cases of the greater occipital neuralgia were randomized into acupuncture group (30 cases) and western medicine group (30 cases). In acupuncture group, acupuncture was applied on Fengchi (风池 GB 20), Chengling (承灵 GB 18), Xuanzhong (悬钟 GB 39) and Ashi (阿是穴), once everyday. In western medicine group, carbamazepine was administrated orally, 100 mg, Bid × 10 days. Results: In acupuncture group, 25 cases (83.3%) were cured, 4 cases (13.3%) remarkably effective, 1 case (3.4%) effective and 0 case ineffective. In western medicine group, 16 cases (53.3%) were cured, 7 cases (23.3%) remarkably effective, 2 cases (6.7%) effective and 5 cases ( 16.7 % ) ineffective. The cured-markedly effective rates of two groups were 96.6 % and 76.6 % respectively, indicating significant difference between two groups ( P < 0.05). Conclusion: The therapeutic effect with acupuncture on the greater occipital neuralgia was significant compared with that with carbamazepine.

  4. Influence of Inorganic Ions and Organic Substances on the Degradation of Pharmaceutical Compound in Water Matrix

    Directory of Open Access Journals (Sweden)

    Edyta Kudlek

    2016-11-01

    Full Text Available The paper determined the influence of inorganic substances and high-molecular organic compounds on the decomposition of diclofenac, ibuprofen, and carbamazepine in the process of photocatalysis conducted with the presence of Titanium dioxide (TiO2. It was determined that the presence of such ions as CO 3 2 − , HCO 3 − , HPO 4 2 − as well as SO 4 2 − inhibited the decomposition of carbamazepine, whereas the efficiency of diclofenac degradation was decreased only by the presence of CO 3 2 − and HCO 3 − anions. In case of ibuprofen sodium salt (IBU, all investigated anions influenced the increase in its decomposition rate. The process of pharmaceutical photooxidation conducted in suspensions with Al3+ and Fe3+ cations was characterized by a significantly decreased efficiency when compared to the solution deprived of inorganic compounds. The addition of Ca2+, Mg2+ and NH4+ affected the increase of reaction rate constant value of diclofenac and ibuprofen decomposition. On the other hand, high molecular organic compounds present in the model effluent additionally catalysed the degradation process of pharmaceutical compounds and constituted an additional sorbent that enabled to decrease their concentration. Toxicological analysis conducted in deionized water with pharmaceutical compounds’ patterns proved the production of by-products from oxidation and/or reduction of micropollutants, which was not observed for model effluent irradiation.

  5. Multidrug resistance-associated protein 1 decreases the concentrations of antiepileptic drugs in cortical extracellular fluid in amygdale kindling rats

    Institute of Scientific and Technical Information of China (English)

    Ying-hui CHEN; Cui-cui WANG; Xia XIAO; Li WEI; Guoxiong XU

    2013-01-01

    Aim:To investigate whether multidrug resistance-associated protein 1 (MRP1) was responsible for drug resistence in refractory epilepsy in amygdale kindling rats.Methods:Rat amygdale kindling was used as a model of refractory epilepsy.The expression of MRP1 mRNA and protein in the brains was examined using RT-PCR and Western blot.MRP1-positive cells in the cortex and hippocampus were studied with immunohistochemical staining.The rats were intraperitoneally injected with phenytoin (50 mg/kg) or carbamazepine (20 mg/kg),and their concentrations in the cortical extracellular fluid were measured using microdialysis and HPLC.Probenecid,a MRP1 inhibitor (40 mmol/L,50 μL) was administered through an inflow tube into the cortex 30 min before injection of the antiepileptic drugs.Results:The expression of MRP1 mRNA and protein was significantly up-regulated in the cortex and hippocampus in amygdale kindling rats compared with the control group.Furthermore,the number of MRP1-positive cells in the cortex and hippocampus was also significantly increased in amygdale kindling rats.Microdialysis studies showed that the concentrations of phenytoin and carbamazepine in the cortical extracellular fluid were significantly decreased in amygdale kindling rats.Pre-administration of probenecid could restore the concentrations back to their control levels.Conclusion:Up-regulation of MRP1 is responsible for the resistance of brain cells to antiepileptic drugs in the amygdale kindling rats.

  6. Complex partial seizures and aphasia as initial manifestations of non-ketotic hyperglycemia: case report Crises parciais complexas e afasia como manifestações iniciais de hiperglicemia não cetótica: relato de caso

    Directory of Open Access Journals (Sweden)

    MARCUS SABRY AZAR BATISTA

    1998-06-01

    Full Text Available We describe a case of non-ketotic hyperglycemia (NKH, heralded by complex partial seizures and aphasia of epileptic origin, besides versive and partial motor seizures. This clinical picture was accompanied by left fronto-temporal spikes in the EEG. The seizures were controlled by carbamazepine only after the control of the diabetes. A month later, carbamazepine was discontinued. The patient remained without seizures, with normal language, using only glybenclamide. Complex partial seizures, opposed to simple partial seizures, are rarely described in association to NKH. Epileptic activity localized over language regions can manifest as aphasia.Descrevemos um caso de hiperglicemia não-cetótica (HNC cujas manifestações iniciais foram crises parciais complexas e afasia de origem epiléptica, além de crises versivas e parcias motoras. Este quadro clínico foi acompanhado por atividade epileptiforme na região fronto-temporal esquerda ao eletrencefalograma. As crises epilépticas foram controladas com carbamazepina (CBZ apenas após o controle do diabetes mellitus. Após um mês, a CBZ foi suspensa, permanecendo a paciente com linguagem normal, sem novas crises epilépticas, em uso apenas de glibenclamida. Crises parciais complexas, ao contrário de crises parciais simples, são raramente descritas como manifestação de HNC. Atividade epileptiforme nas regiões relacionadas a linguagem podem manifestar-se como afasia.

  7. Volume-selective proton MR spectroscopy for in-vitro quantification of anticonvulsants

    Energy Technology Data Exchange (ETDEWEB)

    Braun, J.; Tolxdorff, T. [Inst. of Medical Informatics, Biometry and Epidemiology, University Hospital Benjamin Franklin, Berlin (Germany); Seyfert, S.; Marx, P. [Freie Univ. Berlin (Germany). Abt. fuer Neurologie; Bernarding, J. [Inst. of Medical Informatics, Biometry and Epidemiology, University Hospital Benjamin Franklin, Berlin (Germany); Freie Univ. Berlin (Germany). Klinik fuer Radiologie, Nuklearmedizin und Physikalische Therapie; Schilling, A. [Freie Univ. Berlin (Germany). Klinik fuer Radiologie, Nuklearmedizin und Physikalische Therapie

    2001-03-01

    Administration of anticonvulsant drugs is clinically monitored by checking seizure frequency and by determining the serum concentration of the drug. In a few reports, drug concentrations in brain parenchyma have been determined using ex vivo techniques. Little is known about the in vivo concentration in the brain parenchyma. Our goals were to characterise the NMR spectra of the anticonvulsants at therapeutic concentrations, to determine the minimum detectable concentrations, and to quantify the drugs noninvasively. Volume-selective 1H-MR spectroscopy (MRS) was performed under standard clinical conditions using a single-voxel STEAM (stimulated-echo acquisition mode) sequence at 1.5 T. Spectra of the anticonvulsants carbamazepine, phenobarbital, phenytoin and valproate were acquired in vitro in hydrous solutions at increasing dilution. Phenytoin, phenobarbital and valproate were detectable below maximum therapeutic serum concentrations. Within therapeutic ranges, there was good agreement between concentrations determined by 1H-MRS and those by standard fluorescence polarisation immunoassay. Due to the absence of signals of brain metabolites, the aromatic protons of phenobarbital, phenytoin and carbamazepine, with resonance lines around 7.4 ppm, allow the drugs to be detected. Valproate, with two resonances around 1.2 ppm, should be differentiable from potential brain metabolites using nonlinear analysis of the brain spectrum. Volume-selective 1H-MRS is therefore expected to be able to monitor anticonvulsant therapy in vivo. (orig.)

  8. Modelling On Photogeneration Of Hydroxyl Radical In Surface Waters And Its Reactivity Towards Pharmaceutical Wastes

    Science.gov (United States)

    Das, Radha; Vione, Davide; Rubertelli, Francesca; Maurino, Valter; Minero, Claudio; Barbati, Stéphane; Chiron, Serge

    2010-10-01

    This paper reports a simple model to describe the formation and reactivity of hydroxyl radicals in the whole column of freshwater lakes. It is based on empirical irradiation data and is a function of the water chemical composition (the photochemically significant parameters NPOC, nitrate, nitrite, carbonate and bicarbonate), the lake conformation best expressed as the average depth, and the water absorption spectrum in a simplified Lambert-Beer approach. The purpose is to derive the lifetime of dissolved molecules, due to reaction with •OH, on the basis of their second-order rate constants with the hydroxyl radical. The model was applied to two compounds of pharmaceutical wastes ibuprofen and carbamazepine, for which the second-order rate constants for reaction with the hydroxyl radical were measured by means of the competition kinetics with 2-propanol. The measured values of the rate constants are 1.0×1010 and 1.6×1010M-1 s-1 for ibuprofen and carbamazepine, respectively. The model suggests that the lifetime of a given compound can be very variable in different lakes, even more than the lifetime of different compounds in the same lake. It can be concluded that as far as the reaction with •OH, is concerned the concepts of photolability and photostability, traditionally attached to definite compounds, are ecosystem-dependent at least as much as they depend on the molecule under consideration.

  9. Ozone oxidation of antidepressants in wastewater –Treatment evaluation and characterization of new by-products by LC-QToFMS

    Directory of Open Access Journals (Sweden)

    Lajeunesse André

    2013-01-01

    Full Text Available Abstract Background The fate of 14 antidepressants along with their respective N-desmethyl metabolites and the anticonvulsive drug carbamazepine was examined in a primary sewage treatment plant (STP and following advanced treatments with ozone (O3. The concentrations of each pharmaceutical compound were determined in raw sewage, effluent and sewage sludge samples by LC-MS/MS analysis. The occurrence of antidepressant by-products formed in treated effluent after ozonation was also investigated. Results Current primary treatments using physical and chemical processes removed little of the compounds (mean removal efficiency: 19%. Experimental sorption coefficients (Kd of each studied compounds were also calculated. Sorption of venlafaxine, desmethylvenlafaxine, and carbamazepine on sludge was assumed to be negligible (log Kd ≤ 2, but higher sorption behavior can be expected for sertraline (log Kd ≥ 4. Ozonation treatment with O3 (5 mg/L led to a satisfactory mean removal efficiency of 88% of the compounds. Screening of the final ozone-treated effluent samples by high resolution-mass spectrometry (LC-QqToFMS did confirm the presence of related N-oxide by-products. Conclusion Effluent ozonation led to higher mean removal efficiencies than current primary treatment, and therefore represented a promising strategy for the elimination of antidepressants in urban wastewaters. However, the use of O3 produced by-products with unknown toxicity.

  10. Effect of magnesium oxide on the activity of standard anti-epileptic drugs against experimental seizures in rats

    Directory of Open Access Journals (Sweden)

    Dhande Priti

    2009-01-01

    Full Text Available Objectives : To study the effect of oral magnesium oxide supplementation alone and on the activity of standard anti-epileptic drugs in the animal models of maximal electroshock seizures (MES and chemically (pentylenetetrazole [PTZ]-induced seizures. Methods : Healthy male albino rats were given magnesium oxide (MgO supplementation orally in various doses (500, 750 and 1000 mg/kg /day for 4 weeks (day 1 to day 28. On day 0 and day 29, response to MES (180 mA for 0.2 s was tested 1 h after pre-administration of phenytoin or carbamazepine orally. Similarly, in the other groups, the response to PTZ 40 mg/kg i.p. was tested 1 h after pre-administration of oral sodium valproate. Results : Oral administration of MgO in a low dose (500 mg/kg for 4 weeks in healthy rats appears to exert protective effect against MES. High oral doses of MgO (750 and 1000 mg/kg appear to enhance the activity of phenytoin and carbamazepine in the MES model. MgO supplementation was seen to decrease the latency of PTZ-induced seizures. Conclusion : The dose of oral MgO appears to have an inverse relation with the protective effect in MES-induced seizure model. High doses of MgO supplementation given orally appear to enhance the activity of standard anti-epileptic drugs in the MES-induced seizure model.

  11. NQR investigation and characterization of cocrystals and crystal polymorphs

    Energy Technology Data Exchange (ETDEWEB)

    Seliger, Janez, E-mail: janez.seliger@fmf.uni-lj.si; Zagar, Veselko [Jozef Stefan Institute (Slovenia); Asaji, Tetsuo [Nihon University, Department of Chemistry, College of Humanities and Sciences (Japan)

    2013-05-15

    The application of {sup 14}N NQR to the study of cocrystals and crystal polymorphs is reviewed. In ferroelectric and antiferroelectric organic cocrystals {sup 14}N NQR is used to determine proton position in an N-H...O hydrogen bond and proton displacement below T{sub C}. In cocrystal isonicitinamide - oxalic acid (2:1) {sup 14}N NQR is used to distinguish between two polymorphs and to determine the type of the hydrogen bond (N{sup -}...H-O). The difference in the {sup 14}N NQR spectra of cocrystal formers and cocrystal is investigated in case of carbamazepine, saccharin and carbamazepine - saccharin (1:1). The experimental resolution allows an unambiguous distinction between the {sup 14}N NQR spectrum of the cocrystal and the {sup 14}N NQR spectra of the cocrystal formers. The possibility of application of NQR and double resonance for the determination of the inhomogeneity of the sample and for the study of the life time of an unstable polymorph is discussed.

  12. RP-HPLC estimation of venlafaxine hydrochloride in tablet dosage forms

    Directory of Open Access Journals (Sweden)

    Baldania S

    2008-01-01

    Full Text Available A simple, specific, accurate, and precise reverse phase high performance liquid chromatographic method was developed and validated for the estimation of venlafaxine hydrochloride in tablet dosage forms. A Phenomenex Gemini C-18, 5 µm column having 250 x 4.6 mm i.d. in isocratic mode, with mobile phase containing methanol: 0.05 M potassium dihydrogen orthophosphate (70:30, v/v; pH 6.2 was used. The flow rate was 1.0 ml/min and effluents were monitored at 226 nm. Carbamazepine was used as an internal standard. The retention time of venlafaxine hydrochloride and carbamazepine were 3.7 min and 5.3 min, respectively. The method was validated for specificity, linearity, accuracy, precision, limit of quantification, limit of detection, robustness and solution stability. Limit of detection and limit of quantification for estimation of venlafaxine hydrochloride were found to be 100 ng/ml and 300 ng/ml, respectively. Recoveries of venlafaxine hydrochloride in tablet formulations were found to be in the range of 99.02-101.68%. Proposed method was successfully applied for the quantitative determination of venlafaxine hydrochloride in tablet dosage forms.

  13. Isobolographic analysis of interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and four conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model.

    Science.gov (United States)

    Luszczki, Jarogniew J; Antkiewicz-Michaluk, Lucyna; Czuczwar, Stanislaw J

    2009-01-14

    The anticonvulsant activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MeTHIQ--an endogenous parkinsonism-preventing substance) administered alone and in combination with four conventional antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproate) was determined in the mouse maximal electroshock-induced seizure model. The types of interactions of MeTHIQ with the antiepileptic drugs were characterized using isobolographic analysis. The isobolographic analysis revealed that the combination of MeTHIQ with phenobarbital at the fixed-ratios of 1:3, 1:1 and 3:1 exerted supra-additive (synergistic) interaction in the maximal electroshock-induced seizure test. In contrast, the combinations of MeTHIQ with carbamazepine, phenytoin and valproate exerted additive interaction for all three fixed-ratios (1:3, 1:1 and 3:1) tested in the maximal electroshock-induced seizure test. In conclusion, MeTHIQ produces a clear-cut anticonvulsant effect in the maximal electroshock-induced seizure test in mice. The supra-additive interaction of MeTHIQ with phenobarbital against maximal electroshock-induced seizures makes their combination of pivotal importance from a clinical viewpoint.

  14. Coupling granular activated carbon adsorption with membrane bioreactor treatment for trace organic contaminant removal: breakthrough behaviour of persistent and hydrophilic compounds.

    Science.gov (United States)

    Nguyen, Luong N; Hai, Faisal I; Kang, Jinguo; Price, William E; Nghiem, Long D

    2013-04-15

    This study investigated the removal of trace organic contaminants by a combined membrane bioreactor - granular activated carbon (MBR-GAC) system over a period of 196 days. Of the 22 compounds investigated here, all six hydrophilic compounds with electron-withdrawing functional groups (i.e., metronidazole, carbamazepine, ketoprofen, naproxen, fenoprop and diclofenac) exhibited very low removal efficiency by MBR-only treatment. GAC post-treatment initially complemented MBR treatment very well; however, a compound-specific gradual deterioration of the removal of the above-mentioned problematic compounds was noted. While a 20% breakthrough of all four negatively charged compounds namely ketoprofen, naproxen, fenoprop and diclofenac occurred within 1000-3000 bed volumes (BV), the same level of breakthrough of the two neutral compounds metronidazole and carbamazepine did not occur until 11,000 BV. Single-solute isotherm parameters did not demonstrate any discernible correlation individually with any of the parameters that may govern adsorption onto GAC, such as log D, number of hydrogen-bond donor/acceptor groups, dipole moment or aromaticity ratio of the compounds. The isotherm data, however, could differentiate the breakthrough behaviour between negatively charged and neutral trace organic contaminants.

  15. Wastewater treatment--adsorption of organic micropollutants on activated HTC-carbon derived from sewage sludge.

    Science.gov (United States)

    Kirschhöfer, Frank; Sahin, Olga; Becker, Gero C; Meffert, Florian; Nusser, Michael; Anderer, Gilbert; Kusche, Stepan; Klaeusli, Thomas; Kruse, Andrea; Brenner-Weiss, Gerald

    2016-01-01

    Organic micropollutants (MPs), in particular xenobiotics and their transformation products, have been detected in the aquatic environment and the main sources of these MPs are wastewater treatment plants. Therefore, an additional cleaning step is necessary. The use of activated carbon (AC) is one approach to providing this additional cleaning. Industrial AC derived from different carbonaceous materials is predominantly produced in low-income countries by polluting processes. In contrast, AC derived from sewage sludge by hydrothermal carbonization (HTC) is a regional and sustainable alternative, based on waste material. Our experiments demonstrate that the HTC-AC from sewage sludge was able to remove most of the applied MPs. In fact more than 50% of sulfamethoxazole, diclofenac and bezafibrate were removed from artificial water samples. With the same approach carbamazepine was eliminated to nearly 70% and atrazine more than 80%. In addition a pre-treated (phosphorus-reduced) HTC-AC was able to eliminate 80% of carbamazepine and diclofenac. Atrazine, sulfamethoxazole and bezafibrate were removed to more than 90%. Experiments using real wastewater samples with high organic content (11.1 g m(-3)) succeeded in proving the adsorption capability of phosphorus-reduced HTC-AC.

  16. Signal Transduction in Astrocytes during Chronic or Acute Treatment with Drugs (SSRIs, Antibipolar Drugs, GABA-ergic Drugs, and Benzodiazepines Ameliorating Mood Disorders

    Directory of Open Access Journals (Sweden)

    Leif Hertz

    2014-01-01

    Full Text Available Chronic treatment with fluoxetine or other so-called serotonin-specific reuptake inhibitor antidepressants (SSRIs or with a lithium salt “lithium”, carbamazepine, or valproic acid, the three classical antibipolar drugs, exerts a multitude of effects on astrocytes, which in turn modulate astrocyte-neuronal interactions and brain function. In the case of the SSRIs, they are to a large extent due to 5-HT2B-mediated upregulation and editing of genes. These alterations induce alteration in effects of cPLA2, GluK2, and the 5-HT2B receptor, probably including increases in both glucose metabolism and glycogen turnover, which in combination have therapeutic effect on major depression. The ability of increased levels of extracellular K+ to increase [Ca2+]i is increased as a sign of increased K+-induced excitability in astrocytes. Acute anxiolytic drug treatment with benzodiazepines or GABAA receptor stimulation has similar glycogenolysis-enhancing effects. The antibipolar drugs induce intracellular alkalinization in astrocytes with lithium acting on one acid extruder and carbamazepine and valproic acid on a different acid extruder. They inhibit K+-induced and transmitter-induced increase of astrocytic [Ca2+]i and thereby probably excitability. In several cases, they exert different changes in gene expression than SSRIs, determined both in cultured astrocytes and in freshly isolated astrocytes from drug-treated animals.

  17. The distribution dynamics and desorption behaviour of mobile pharmaceuticals and caffeine to combined sewer sediments.

    Science.gov (United States)

    Hajj-Mohamad, M; Darwano, H; Duy, S Vo; Sauvé, S; Prévost, M; Arp, H P H; Dorner, S

    2017-01-01

    Pharmaceuticals are discharged to the environment from wastewater resource recovery facilities, sewer overflows, and illicit sewer connections. To understand the fate of pharmaceuticals, there is a need to better understand their sorption dynamics to suspended sediments (SS) and settled sediments (StS) in sewer systems. In this study, such sorption dynamics to both SS and StS were assessed using a batch equilibrium method under both static and dynamic conditions. Experiments were performed with natively occurring and artificially modified concentrations of sewer pharmaceuticals (acetaminophen, theophylline, carbamazepine, and a metabolite of carbamazepine) and caffeine. Differences in apparent distribution coefficients, Kd,app, between SS and StS were related to differences in their organic carbon (OC) content, and the practice of artificially modifying the concentration. Kd,app values of modified contaminant concentrations and high OC sediments were substantially higher. Pseudo-second order desorption rates for these mobile compounds were also quantified. Successive flushing events to simulate the addition of stormwater to sewer networks revealed that aqueous concentrations would not necessarily decrease, because the added water will rapidly return to equilibrium concentrations with the sediments. Sorption and desorption kinetics must be considered in addition to dilution, to avoid underestimating the influence of dilution on concentrations of pharmaceuticals discharged to the environment.

  18. The benefits of powdered activated carbon recirculation for micropollutant removal in advanced wastewater treatment.

    Science.gov (United States)

    Meinel, F; Zietzschmann, F; Ruhl, A S; Sperlich, A; Jekel, M

    2016-03-15

    PAC adsorption is a widespread option for the removal of organic micropollutants (OMP) from secondary effluent. For an optimal exploitation of the adsorption capacity, PAC recirculation is nowadays a common practice, although the mechanistic interrelations of the complex recirculation process are not fully resolved. In this work, extensive multi-stage batch adsorption testing with repeated PAC and coagulant dosage was performed to evaluate the continuous-flow recirculation system. Partly loaded PAC showed a distinct amount of remaining capacity, as OMP and DOC removals considerably increased with each additional adsorption stage. At a low PAC dose of 10 mg PAC L(-1), removals of benzotriazole and carbamazepine were shown to rise from 80% in the 11th stage at 30 min adsorption time per stage. At a high PAC dose of 30 mg PAC L(-1), OMP and DOC removals were significantly higher and reached 98% (for benzotriazole and carbamazepine) after 11 stages. Coagulant dosage showed no influence on OMP removal, whereas a major part of DOC removal can be attributed to coagulation. Multi-stage adsorption is particularly beneficial for small PAC doses and significant PAC savings are feasible. A new model approach for predicting multi-stage OMP adsorption on the basis of a single-stage adsorption experiment was developed. It proved to predict OMP removals and PAC loadings accurately and thus contributes towards understanding the PAC recirculation process.

  19. Small-Scale Assays for Studying Dissolution of Pharmaceutical Cocrystals for Oral Administration.

    Science.gov (United States)

    Box, Karl J; Comer, John; Taylor, Robert; Karki, Shyam; Ruiz, Rebeca; Price, Robert; Fotaki, Nikoletta

    2016-04-01

    The purpose of this study was to better understand the dissolution properties and precipitation behavior of pharmaceutical cocrystals of poorly soluble drugs for the potential for oral administration based on a small-scale dissolution assay. Carbamazepine and indomethacin cocrystals with saccharin and nicotinamide as coformers were prepared with the sonic slurry method. Dissolution of the poorly soluble drugs indomethacin and carbamazepine and their cocrystals was studied with a small-scale dissolution assay installed on a SiriusT3 instrument. Two methodologies were used: (i) surface dissolution of pressed tablet (3 mm) in 20 mL running for fixed times at four pH stages (pH 1.8, pH 3.9, pH 5.4, pH 7.3) and (ii) powder dissolution (2.6 mg) in 2 mL at a constant pH (pH 2). Improved dissolution and useful insights into precipitation kinetics of poorly soluble compounds from the cocrystal form can be revealed by the small-scale dissolution assay. A clear difference in dissolution/precipitation behaviour can be observed based on the characteristics of the coformer used.

  20. Late season pharmaceutical fate in wetland mesocosms with and without phosphorous addition.

    Science.gov (United States)

    Cardinal, Pascal; Anderson, Julie C; Carlson, Jules C; Low, Jennifer E; Challis, Jonathan K; Wong, Charles S; Hanson, Mark L

    2016-11-01

    The fate of six human-use drugs was assessed and predicted in mesocosms designed to mimic shallow constructed wetlands during the onset of fall and senescence. Mesocosms were monitored for 28 days after the addition of carbamazepine, clofibric acid, fluoxetine and naproxen (nominal initial concentrations of 5 μg/L each), sulfamethoxazole, and sulfapyridine (nominal initial concentrations of 150 μg/L each), with and without phosphorous (P) addition at 1.6 mg/L. We hypothesized that addition of P would stimulate primary productivity and enhance removal of pharmaceuticals from the water column. Carbamazepine, clofibric acid, fluoxetine, and naproxen had half-lives of 8.7, 11, 1.5, and 2.5, and 8.6, 11.0, 1.4, and 2.5 days in treatments with and without P amendment, respectively. Sulfamethoxazole and sulfapyridine had half-lives of 17 and 4.9 days in mesocosms with P amendment and 17 and 4.7 days without amendment. A concurrent pulse of P with pharmaceuticals did not significantly enhance the removal of these compounds. Predicted half-lives from modeling efforts were consistent with observed values, with photolysis the greatest contributor to chemical attenuation.

  1. Drug therapy during pregnancy.

    Science.gov (United States)

    Niebyl, J R

    1992-02-01

    A randomized prospective trial has shown that folic acid started before conception and continued for the first trimester reduces the risk of recurrence of neural tube defects by 72% in women with a previously affected child. Carbamazepine exposure in utero is associated with a 1% risk of spina bifida. Long-term follow-up of antenatal exposure to phenobarbital and carbamazepine in two groups of infants shows no neurologic differences between the two groups. Magnesium sulfate is more effective in prevention of recurrent eclamptic seizures than phenytoin. During pregnancy, the need for thyroxine increases in many women. Vitamin B6 and ginger are both effective for nausea and vomiting in early pregnancy. Low-dose aspirin does not change the course of preeclampsia when it is started after the diagnosis is made. Angiotensin-converting enzyme inhibitors cause significant disturbances of fetal and neonatal renal function. Prophylactic beta-adrenergic agents fail to prevent prematurity in twins. Oral tocolysis with magnesium chloride or ritodrine is no more effective than observation alone. The risk of primary pulmonary hypertension in the newborn after indomethacin tocolysis is increased with prolonged therapy. Lithium causes polyhydramnios from fetal diabetes insipidus in utero. Treatment of Ureaplasma urealyticum infection with erythromycin during pregnancy does not eliminate the organism from the lower genital tract and does not improve perinatal outcome.

  2. A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

    Science.gov (United States)

    Pawluk, Shane Ashley; Roels, Craig Allan; Wilby, Kyle John; Ensom, Mary H H

    2015-04-01

    Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.

  3. Do no harm - But first we need to know more: The case of adverse drug reactions with antiepileptic drugs

    Directory of Open Access Journals (Sweden)

    Gagandeep Singh

    2011-01-01

    Full Text Available An adverse drug reaction (ADR is defined by the World Health Organization as a noxious, unintended, and undesired drug effect, when used for therapeutic purposes in humans. ADRs to anti-epileptic drugs (AEDs significantly impact the quality of life of people with epilepsy and account for a little less than half of all recorded treatment failures with AEDs. Hence prevention and early recognition of ADRs constitute an important aspect of management of epilepsy. Recent developments have improved our ability to predict and hence potentially prevent the occurrence of some of the serious ADRs to AEDs. One example is the potential prediction of the risk of severe cutaneous hypersensitivity reactions including Stevens Johnson syndrome and toxic epidermal necrolysis by testing for expression of HLA BFNx011502 allele in people of Asian origin who are prescribed carbamazepine. The association between HLA BFNx011502 expression and carbamazepine skin reactions has been documented in India but the role of HLA testing in Indian populations needs to be clarified in larger studies across different ethnic groups within the country.

  4. Pharmacokinetic interactions between contraceptives and antiepileptic drugs

    DEFF Research Database (Denmark)

    Sabers, A.

    2008-01-01

    The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin and phenoba......The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... and phenobarbital), are strong inducers of the hepatic cytochrome P450 (CYP) 3A4 enzyme system, and are associated with increased the risk of contraceptive failure. In addition, it is demonstrated that also some of the newer AEDs, oxcarbazepine and topiramate influence on the pharmacokinetics of OCs, which...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...

  5. Quantitative dynamic nuclear polarization-NMR on blood plasma for assays of drug metabolism.

    Science.gov (United States)

    Lerche, Mathilde H; Meier, Sebastian; Jensen, Pernille R; Hustvedt, Svein-Olaf; Karlsson, Magnus; Duus, Jens Ø; Ardenkjaer-Larsen, Jan H

    2011-01-01

    Analytical platforms for the fast detection, identification and quantification of circulating drugs with a narrow therapeutic range are vital in clinical pharmacology. As a result of low drug concentrations, analytical tools need to provide high sensitivity and specificity. Dynamic nuclear polarization-NMR (DNP-NMR) in the form of the hyperpolarization-dissolution method should afford the sensitivity and spectral resolution for the direct detection and quantification of numerous isotopically labeled circulating drugs and their metabolites in single liquid-state NMR transients. This study explores the capability of quantitative in vitro DNP-NMR to assay drug metabolites in blood plasma. The lower limit of detection for the anti-epileptic drug (13)C-carbamazepine and its pharmacologically active metabolite (13)C-carbamazepine-10,11-epoxide is 0.08 µg/mL in rabbit blood plasma analyzed by single-scan (13)C DNP-NMR. An internal standard is used for the accurate quantification of drug and metabolite. Comparison of quantitative DNP-NMR data with an established analytical method (liquid chromatography-mass spectrometry) yields a Pearson correlation coefficient r of 0.99. Notably, all DNP-NMR determinations were performed without analyte derivatization or sample purification other than plasma protein precipitation. Quantitative DNP-NMR is an emerging methodology which requires little sample preparation and yields quantitative data with high sensitivity for therapeutic drug monitoring.

  6. Preliminary assessment of terrestrial microalgae isolated from lichens as testing species for environmental monitoring: lichen phycobionts present high sensitivity to environmental micropollutants.

    Science.gov (United States)

    Domínguez-Morueco, N; Moreno, H; Barreno, E; Catalá, M

    2014-01-01

    Bioassays constitute a tool for pollution analysis providing a holistic approach and high-quality indication of the toxicity. Microbioassays allow evaluating the toxicity of many samples, implying lower costs and enabling routine monitoring and pollution control. But tests conducted so far are limited to the use of a small number of taxa. Lichens are excellent bioindicators of pollution with great ecological significance. Studies show that the phycobiont is more sensitive to pollutants than the mycobiont. Phycobiont have features such as adaptation to anhydrobiosis and relatively rapid growth in vitro, making them suitable for microbioassays. Our aim is to determine the sensitivity of phycobionts to the pharmaceutical micropollutants carbamazepine and diclofenac as a preliminary step for the development of a toxicity microbioassay based on phycobionts. Optical dispersion and chlorophyll autofluorescence were used as endpoints of toxicity on two algal species showing that suspensions present cyclic and taxon specific patterns of aggregation. Trebouxia TR9 suspensions present a very high grade of aggregation while Asterochloris erici cells do not. Both micropollutants alter optical properties of the suspensions of both species. No significant alteration of chlorophyll autofluorescence by carbamazepine is observed. A. erici chlorophyll autofluorescence is extremely sensitive to diclofenac but the effect is not dependent on the drug concentration or on the time of exposure. Differently, TR9 only shows punctual chlorophyll alterations. Fluctuations in optical dispersion may indicate changes in the population structure of the species, including reproductive strategy. A. erici seems more sensitive to micropollutants, is better characterized and is available from commercial collections.

  7. Use of pharmaceuticals and pesticides to constrain nutrient sources in coastal groundwater of northwestern Long Island, New York, USA

    Science.gov (United States)

    Zhao, S.; Zhang, P.; Crusius, J.; Kroeger, K.D.; Bratton, J.F.

    2011-01-01

    In developed, non-agricultural, unsewered areas, septic systems and fertilizer application to lawns and gardens represent two major sources of nitrogen to coastal groundwater, in addition to atmospheric input. This study was designed to distinguish between these two possible nitrogen sources by analyzing groundwater samples for pharmaceutical residuals, because fertilizers do not contain any of these pharmaceuticals, but domestic wastewater commonly does. In addition, several herbicides and insecticides used in lawn treatment were analyzed as indicators of nitrogen delivery to groundwater from fertilizers. Groundwater samples were taken through piezometres at shoreline sites in unsewered areas surrounding Northport Harbor and in sewered areas adjacent to Manhasset Bay (hereafter referred to as "Northport" and "Manhasset", respectively), both in northwestern Long Island, USA. Excessive nitrogen loading has led to reduced dissolved oxygen concentrations in Long Island Sound, and the groundwater contribution to the nitrogen budget is poorly constrained. The frequent detection of the anticonvulsant compound carbamazepine in groundwater samples of the Northport Harbor area (unsewered), together with the fact that few pesticides associated with lawn applications were detected, suggests that wastewater input and atmospheric input are the likely sources of nitrogen in the Northport groundwater. High concentrations of nitrogen were also detected in the Manhasset (sewered) groundwater. The low detection frequency and concentration of carbamazepine, however, suggest that the sewer system effectively intercepts nitrogen from wastewater there. The likely sources of nitrogen in the Manhasset groundwater are atmospheric deposition and lawn fertilizers, as this area is densely populated.

  8. Fate of pharmaceuticals and pesticides in fly larvae composting

    Energy Technology Data Exchange (ETDEWEB)

    Lalander, C., E-mail: cecilia.lalander@slu.se [Department of Energy and Technology, Swedish University of Agricultural Sciences (Sweden); Senecal, J.; Gros Calvo, M. [Department of Energy and Technology, Swedish University of Agricultural Sciences (Sweden); Ahrens, L.; Josefsson, S.; Wiberg, K. [Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences (Sweden); Vinnerås, B. [Department of Energy and Technology, Swedish University of Agricultural Sciences (Sweden)

    2016-09-15

    A novel and efficient organic waste management strategy currently gaining great attention is fly larvae composting. High resource recovery efficiency can be achieved in this closed-looped system, but pharmaceuticals and pesticides in waste could potentially accumulate in every loop of the treatment system and spread to the environment. This study evaluated the fate of three pharmaceuticals (carbamazepine, roxithromycin, trimethoprim) and two pesticides (azoxystrobin, propiconazole) in a fly larvae composting system and in a control treatment with no larvae. It was found that the half-life of all five substances was shorter in the fly larvae compost (< 10% of control) and no bioaccumulation was detected in the larvae. Fly larvae composting could thus impede the spread of pharmaceuticals and pesticides into the environment. - Highlights: • Degradation of pharmaceuticals and pesticides in fly larvae composting (FLC). • Half-life considerably shorter in FLC than in control with no larvae. • Half-life of carbamazepine was less than two days in FLC. • No bioaccumulation in larvae detected. • FLC could impede the spreading of pharmaceuticals and pesticide in the environment.

  9. Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center

    Directory of Open Access Journals (Sweden)

    Priscila de Freitas-Lima

    2013-11-01

    Full Text Available Objective To evaluate the utilization profile of antiepileptic drugs in a population of adult patients with refractory epilepsy attending a tertiary center. Method Descriptive analyses of data were obtained from the medical records of 112 patients. Other clinical and demographic characteristics were also registered. Results Polytherapies with ≥3 antiepileptic drugs were prescribed to 60.7% of patients. Of the old agents, carbamazepine and clobazam were the most commonly prescribed (72.3% and 58.9% of the patients, respectively. Among the new agents, lamotrigine was the most commonly prescribed (36.6% of the patients. At least one old agent was identified in 103 out of the 104 polytherapies, while at least one new agent was prescribed to 70.5% of the population. The most prevalent combination was carbamazepine + clobazam + lamotrigine. The mean AED load found was 3.3 (range 0.4–7.7. Conclusion The pattern of use of individual drugs, although consistent with current treatment guidelines, is strongly influenced by the public health system.

  10. Biotransformation of pharmaceuticals under nitrification, nitratation and heterotrophic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Fontaina, E., E-mail: eduardo.fernandez.fontaina@usc.es [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Gomes, I.B. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain); Aga, D.S. [Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Omil, F.; Lema, J.M.; Carballa, M. [Department of Chemical Engineering, Institute of Technology, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain)

    2016-01-15

    The effect of nitrification, nitratation and heterotrophic conditions on the biotransformation of several pharmaceuticals in a highly enriched nitrifying activated sludge was evaluated in this study by selective activation of ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and heterotrophic bacteria. Nitrifiers displayed a noticeable capacity to process ibuprofen due to hydroxylation by ammonia monooxygenase (AMO) to produce 2-hydroxy-ibuprofen. Naproxen was also biotransformed under nitrifying conditions. On the other hand, heterotrophic bacteria present in the nitrifying activated sludge (NAS) biotransformed sulfamethoxazole. In contrast, both nitrifying and heterotrophic activities were ineffective against diclofenac, diazepam, carbamazepine and trimethoprim. Similar biotransformation rates of erythromycin, roxithromycin and fluoxetine were observed under all conditions tested. Overall, results from this study give more evidence on the role of the different microbial communities present in activated sludge reactors on the biological removal of pharmaceuticals. - Highlights: • The removal of pharmaceuticals in nitrifying activated sludge (NAS) was studied. • Nitrifying activity increases biotransformation rate of ibuprofen and naproxen. • Hydroxylation of ibuprofen by ammonia monooxygenase of ammonia oxidizing bacteria • Heterotrophic activity enhances biotransformation of sulfamethoxazole in NAS. • Recalcitrance of trimethoprim, diclofenac, carbamazepine and diazepam in NAS.

  11. Assessment of the mechanisms involved in the removal of emerging contaminants by microalgae from wastewater: a laboratory scale study.

    Science.gov (United States)

    Matamoros, Víctor; Uggetti, Enrica; García, Joan; Bayona, Josep M

    2016-01-15

    Aerated batch reactors (2.5L) fed either with urban or synthetic wastewater were inoculated with microalgae (dominated by Chlorella sp. and Scenedesmus sp.) to remove caffeine, ibuprofen, galaxolide, tributyl phosphate, 4-octylphenol, tris(2-chloroethyl) phosphate and carbamazepine for 10 incubation days. Non-aerated and darkness reactors were used as controls. Microalgae grew at a rate of 0.25 d(-1) with the complete removal of N-NH4 during the course of the experiment. After 10 incubation days, up to 99% of the microcontaminants with a Henry's law constant higher than 3 10(-1) Pa m(3) mol(-1) (i.e., 4-octylphenol, galaxolide, and tributyl phosphate) were removed by volatilization due to the effect of air stripping. Whereas biodegradation was effective for removing ibuprofen and caffeine, carbamazepine and tris(2-chloroethyl) phosphate behaved as recalcitrant compounds. The use of microalgae was proved to be relevant for increasing the biodegradation removal efficiency of ibuprofen by 40% and reducing the lag phase of caffeine by 3 days. Moreover, the enantioselective biodegradation of S-ibuprofen suggested a biotic prevalent removal process, which was supported by the identification of carboxy-ibuprofen and hydroxy-ibuprofen. The results from microalgae reactors fed with synthetic wastewater showed no clear evidences of microalgae uptake of any of the studied microcontaminants.

  12. Comparative uptake and translocation of pharmaceutical and personal care products (PPCPs) by common vegetables.

    Science.gov (United States)

    Wu, Xiaoqin; Ernst, Frederick; Conkle, Jeremy L; Gan, Jay

    2013-10-01

    Reuse of treated wastewater to irrigate agricultural crops is increasing in many arid and semi-arid areas around the world. The presence of numerous pharmaceutical and personal care products (PPCPs) in treated wastewater and their potential transfer into food produce such as vegetables poses an unknown human health risk. The goal of this study was to identify PPCPs that have a comparatively high potential for plant uptake and translocation. A total of 20 frequently-occurring PPCPs were compared for their accumulation into four staple vegetables (lettuce, spinach, cucumber, and pepper) grown in nutrient solutions containing PPCPs at 0.5 or 5μgL(-1). Triclocarban, fluoxetine, triclosan, and diazepam were found at high levels in roots, while meprobamate, primidone, carbamazepine, dilantin, and diuron exhibited more active translocation from roots to leaves. Root uptake of neutral PPCPs was positively correlated with the pH adjusted log Kow(i.e., log Dow), and was likely driven by chemical adsorption onto the root surfaces. In contrast, translocation from roots to leaves was negatively related to log Dow, suggesting hydrophilicity-regulated transport via xylems. Compounds preferentially sorbed to roots should be further evaluated for their uptake in tuber vegetables (e.g., carrot, radish) under field conditions, while those easily translocated into leaves (e.g., carbamazepine, dilantin) merit focused consideration for leafy and other vegetables (e.g., lettuce, cucumber). However, estimation of dietary intake by humans suggested the implied risks from exposure to PPCPs via wastewater irrigation to be negligible.

  13. Recurrence and Relapse in Bipolar Mood Disorder

    Directory of Open Access Journals (Sweden)

    S Gh Mousavi

    2004-06-01

    Full Text Available Background: Despite the effectiveness of pharmacotherapy in acute phase of bipolar mood disorder, patients often experience relapses or recurrent episodes. Hospitalization of patients need a great deal of financial and humanistic resources which can be saved through understanding more about the rate of relapse and factors affecting this rate. Methods: In a descriptive analytical study, 380 patients with bipolar disorder who were hospitalized in psychiatric emergency ward of Noor hospital, Isfahan, Iran, were followed. Each patient was considered for; the frequency of relapse and recurrence, kind of pharmachotherapy, presence of psychotherapeutic treatments, frequency of visits by psychiatrist and the rank of present episode. Results: The overall prevalence of recurrence was 42.2%. Recurrence was lower in patients using lithium carbonate or sodium valproate or combined therapy (about 40%, compared to those using carbamazepine (80%. Recurrence was higher in patients treated with only pharmacotherapy (44.5% compared to those treated with both pharmacotherapy and psychotherapy (22.2%. Patients who were visited monthy by psychiatrist had lower rate of recurrence compared to those who had irregular visits. Conclusion: The higher rate of recurrence observed in carbamazepine therapy may be due to its adverse reactions and consequently poor compliance to this drug. Lower rates of recurrence with psychotherapy and regular visits may be related to the preventive effects of these procedures and especially to the effective management of stress. Keywords: Bipolar Mood Disorder, Recurrence, Relapse.

  14. Treating mood disorders during pregnancy: safety considerations.

    Science.gov (United States)

    Eberhard-Gran, Malin; Eskild, Anne; Opjordsmoen, Stein

    2005-01-01

    Mood disorders in pregnancy may have a negative effect on self care and pregnancy outcome that affects the mother directly and the child indirectly. Thus, some women may require pharmacological treatment. Pharmacotherapy of mood disorders during pregnancy implies specific considerations. This paper presents an updated review of available studies on the treatment of mood disorders and present knowledge on teratogenicity, neonatal effects and long-term neurobehavioural effects for the different psychotropic drugs, including treatment with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), other antidepressants, benzodiazepines, lithium, carbamazepine/valproic acid, lamotrigine and novel antipsychotics. However, the existing knowledge on the use of antidepressants and mood stabilising agents during pregnancy is hampered by a lack of results from randomised controlled trials.SSRIs and TCAs have not been associated with an increased risk of major malformations, but poor neonatal adaptation has been described. Benzodiazepines used in the first trimester have been associated with orofacial clefts. Mood stabilisers such as lithium, carbamazepine and valproic acid (sodium valproate) are associated with an increased risk of fetal malformations. Both benzodiazepines and lithium may cause adaptation problems in the newborn. In utero exposure to novel antipsychotics has not been associated with congenital malformations; however, the data are still limited. The knowledge about long-term neurobehavioural effects in the offspring is still limited for all agents and requires further investigation. Possible adverse effects of fetal exposure must be balanced against the adverse effects of an untreated maternal mood disorder.

  15. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design.

    Science.gov (United States)

    Chiron, Catherine; Tonnelier, Sylvie; Rey, Elisabeth; Brunet, Marie-Lucie; Tran, Agnes; d'Athis, Philippe; Vincent, Jean; Dulac, Olivier; Pons, Gerard

    2006-06-01

    Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.

  16. Mitigation of micropollutants for black water application in agriculture via composting of anaerobic sludge.

    Science.gov (United States)

    Butkovskyi, A; Ni, G; Hernandez Leal, L; Rijnaarts, H H M; Zeeman, G

    2016-02-13

    The excess sludge from Up-flow anaerobic sludge bed (UASB) reactor operated on source separated toilet wastewater is a potential source of nutrients and organic matter. It can be further stabilized and dried by composting and applied as a soil amendment. Presence of pathogens, heavy metals and micropollutants in the compost derived from anaerobic sludge is thus undesirable. This paper focuses on removal of micropollutants, typically present in domestic wastewater, via composting of UASB sludge with waste wood. Estrone, diclofenac, ibuprofen, metoprolol, carbamazepine, galaxolide and triclosan were spiked to a mixture of UASB sludge and waste wood. Their concentrations were monitored during 92 days of composting at controlled temperature conditions. All studied micropollutants were removed at various rates with overall removal ranging from 99.9% for ibuprofen, diclofenac and estrone to 87.8% for carbamazepine. Accumulation of methyltriclosan as by-product of triclosan degradation was observed. The prospects and limitations of the integration of a composting process into Source Separated Sanitation concepts are discussed.

  17. Qualitative and quantitative study of polymorphic forms in drug formulations by near infrared FT-Raman spectroscopy

    Science.gov (United States)

    Auer, Martin E.; Griesser, Ulrich J.; Sawatzki, Juergen

    2003-12-01

    Near infrared FT-Raman spectroscopy was applied for the determination of polymorphic forms in a number of commercial drug products containing the polymorphic drug compounds sorbitol, mannitol, famotidine, acemetacin, carbamazepine, meprobamate and phenylbutazone. The crystal forms present in the drug products were identified based on the position, intensity and shape of characteristic bands. Quantitative analysis of a mixture of two crystal forms of mannitol in a drug product was carried out using a partial least-squares method. In drug products containing meprobamate, sorbitol, and carbamazepine, the thermodynamically stable form was found exclusively, whereas metastable polymorphs were found in solid dosage forms of acemetacin, phenylbutazone, famotidine and mannitol. A mixture of two polymorphic forms of mannitol in Lipobay tablets was determined to consist of 30.8±3.8% of the metastable modification I. The simple sample preparation, the occurrence of sharp bands in the spectra as well as the high reproducibility and accuracy qualifies FT-Raman spectroscopy for the identification and quantification of crystal forms in drug products. The method is perfectly suited to meet the regulatory requirements of monitoring crystal forms during processing and storage and often succeeds in detecting the present crystal form in drug products even when the used excipients are not known.

  18. Occurrence and behavior of pharmaceuticals, steroid hormones, and endocrine-disrupting personal care products in wastewater and the recipient river water of the Pearl River Delta, South China.

    Science.gov (United States)

    Yu, Yiyi; Huang, Qiuxin; Wang, Zhifang; Zhang, Kun; Tang, Caiming; Cui, Jianlan; Feng, Jialiang; Peng, Xianzhi

    2011-04-01

    The occurrence and behavior of β-blockers, antiepileptic drug carbamazepine and its metabolites, X-ray contrast agent iopromide, natural and synthetic hormones, and several groups of hormone-like personal care products (PCPs), including antiseptics (triclocarban, triclosan, and 2-phenylphenol), parabens and bisphenol A, were investigated in municipal wastewater, sewage sludge, and urban river water of the Pearl River Delta, South China. The pharmaceuticals, natural hormones and PCPs were ubiquitously detected in the raw wastewater from a sewage treatment plant (STP). Only triclocarban and triclosan were detected at significant amounts in the dewatered sludge. Iopromide and the PCPs were greatly removed/transformed from the aqueous phase of the wastewater. The β-blockers were only moderately removed/transformed. Carbamazepine passed through the STP almost unchanged. Biodegradation was the dominant process for elimination/transformation of the pharmaceuticals, hormones, and most PCPs in the STP. However, sorption also played an important role in the fate of triclocarban with nearly 50% of the mass load entering the STP ended up and persisted in the dewatered sludge. The pharmaceuticals, estrone, and PCPs were also widely detected in the Pearl River at Guangzhou. Bisphenol A had the highest concentration. The pharmaceutical concentrations in the Pearl River were higher in March than in May, most likely due to less dilution by lower precipitation. The omnipresence and high levels of the pharmaceuticals and PCPs in the Pearl River may be associated with direct discharge of untreated wastewater and pose potential risks to the ecological system.

  19. Pharmaceuticals, alkylphenols and pesticides in Mediterranean coastal waters: Results from a pilot survey using passive samplers

    Science.gov (United States)

    Munaron, Dominique; Tapie, Nathalie; Budzinski, Hélène; Andral, Bruno; Gonzalez, Jean-Louis

    2012-12-01

    21 pharmaceuticals, 6 alkylphenols and 27 hydrophilic pesticides and biocides were investigated using polar organic contaminant integrative samplers (POCIS) during a large-scale study of contamination of French Mediterranean coastal waters. Marine and transitional water-bodies, defined under the EU Water Framework Directive were monitored. Our results show that the French Mediterranean coastal waters were contaminated with a large range of emerging contaminants, detected at low concentrations during the summer season. Caffeine, carbamazepine, theophilline and terbutaline were detected with a detection frequency higher than 83% in the coastal waters sampled, 4-nonylphenol (4-NP), 4-tert-octylphenol (4-OP) and 4-nonylphenol diethoxylate (NP2EO) were detected in all coastal waters sampled, and diuron, terbuthylazine, atrazine, irgarol and simazine were detected in more than 77% of samples. For pharmaceuticals, highest time-weighted average (TWA) concentrations were measured for caffeine and carbamazepine (32 and 12 ng L-1, respectively). For alkylphenols, highest TWA concentrations were measured for 4-nonylphenol mono-ethoxylate and 4-nonylphenol (41 and 33 ng L-1, respectively), and for herbicides and biocides, they were measured for diuron and irgarol (33 and 2.5 ng L-1, respectively). Except for Diana lagoon, lagoons and semi-enclosed bays were the most contaminated areas for herbicides and pharmaceuticals, whilst, for alkylphenols, levels of contamination were similar in lagoons and coastal waters. This study demonstrates the relevance and utility of POCIS as quantitative tool for measuring low concentrations of emerging contaminants in marine waters.

  20. Corrigendum to “Sorption/desorption of non-hydrophobic and ionisable pharmaceutical and personal care products from reclaimed water onto/from a natural sediment” Sci Total Environ 472 (2014) 273–281

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Hernández, Virtudes, E-mail: virtudes.martinez@imdea.org [IMDEA Agua, Madrid Institute for Advanced Studies in Water, Parque Científico Tecnológico de la Universidad de Alcalá, 28805 Alcalá de Henares, Madrid (Spain); Meffe, Raffaella; Herrera, Sonia [IMDEA Agua, Madrid Institute for Advanced Studies in Water, Parque Científico Tecnológico de la Universidad de Alcalá, 28805 Alcalá de Henares, Madrid (Spain); Arranz, Elena [University of Alcalá, Geography and Geology Department, 28871 Alcalá de Henares, Madrid (Spain); Bustamante, Irene de [IMDEA Agua, Madrid Institute for Advanced Studies in Water, Parque Científico Tecnológico de la Universidad de Alcalá, 28805 Alcalá de Henares, Madrid (Spain); University of Alcalá, Geography and Geology Department, 28871 Alcalá de Henares, Madrid (Spain)

    2015-02-01

    In the present work, the sorption of pharmaceutical and personal care products (PPCPs) (acetaminophen, atenolol, carbamazepine, caffeine, naproxen and sulphamethoxazole) onto the natural organic matter (NOM) and the inorganic surfaces of a natural sandy loam sediment was quantified separately. The quantification was based on the PPCP charge, their degree of ionisation, their octanol-water partitioning coefficient (K{sub OW}) and the sediment organic carbon fraction (ƒ{sub OC}). PPCP desorption from the sediment was examined under conditions of infiltrating water containing a high concentration of inorganic ions (mimicking infiltrating reclaimed water), and a low concentration (and smaller diversity) of inorganic ions (mimicking rainwater infiltration). Batch tests were performed using a sediment/water ratio of 1:4 and a PPCP initial concentration ranging from 1 to 100 μg L{sup −1}. The results showed the type and degree of PPCP ionisation to strongly influence the sorption of these compounds onto the sediment. The sorption of cationic species onto the sediment was higher than that of anionic species and mostly reversible; the sorption of neutral species was negligible with the exception of caffeine. The anionic species sorbed less onto the sediment, but also desorbed less easily. Most of the compounds showed a sorption that was highly influenced by interaction with mineral surfaces. The presence of inorganic ions had no impact on the desorption of the PPCPs from the sediment. According to the calculated percentages of removal, the mobility followed the order: carbamazepine > acetaminophen > naproxen > atenolol > sulphamethoxazole > caffeine.

  1. Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood.

    Science.gov (United States)

    Aynaci, F M; Orhan, F; Orem, A; Yildirmis, S; Gedik, Y

    2001-05-01

    Antiepileptic drugs may alter plasma lipid status in epileptic patients. We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on plasma levels of lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B in 22 epileptic children. The children were separated as group 1, seven children, mean age 1.6+/-0.2 years, treated with phenobarbital, 5 mg/kg/day, twice daily; group 2, seven children, mean age 9.8+/-1.2 years, treated with carbamazepine, 20 mg/kg/day, twice daily; and group 3, eight children, mean age 6.8+/-0.6 years, treated with valproate, 20 mg/kg/day, twice daily. Plasma lipoprotein (a) and other lipid levels were studied before (pretreatment) and at 3 and 6 months of treatment. Friedman two-way analysis of variance and Wilcoxon's signed-rank test were used for statistical analysis, and the results were expressed as the mean and standard error of the mean. The mean age of children in group 1 was significantly low, compared with groups 2 and, 3 (P < .001). The mean pretreatment lipid levels between the groups were not significant. The increase in lipoprotein (a) at 3 and 6 months and high-density lipoprotein cholesterol at 6 months was statistically significant in group 1 (P < .025). We suggest a careful monitoring of plasma levels of lipoprotein (a) and other lipids in epileptic children treated with antiepileptic drugs.

  2. Update on the Genetic Polymorphisms of Drug-Metabolizing Enzymes in Antiepileptic Drug Therapy

    Directory of Open Access Journals (Sweden)

    Junji Saruwatari

    2010-08-01

    Full Text Available Genetic polymorphisms in the genes that encode drug-metabolizing enzymes are implicated in the inter-individual variability in the pharmacokinetics and pharmaco-dynamics of antiepileptic drugs (AEDs. However, the clinical impact of these polymorphisms on AED therapy still remains controversial. The defective alleles of cytochrome P450 (CYP 2C9 and/or CYP2C19 could affect not only the pharmacokinetics, but also the pharmacodynamics of phenytoin therapy. CYP2C19 deficient genotypes were associated with the higher serum concentration of an active metabolite of clobazam, N-desmethylclobazam, and with the higher clinical efficacy of clobazam therapy than the other CYP2C19 genotypes. The defective alleles of CYP2C9 and/or CYP2C19 were also found to have clinically significant effects on the inter-individual variabilities in the population pharmacokinetics of phenobarbital, valproic acid and zonisamide. EPHX1 polymorphisms may be associated with the pharmacokinetics of carbamazepine and the risk of phenytoin-induced congenital malformations. Similarly, the UDP-glucuronosyltransferase 2B7 genotype may affect the pharmacokinetics of lamotrigine. Gluthatione S-transferase null genotypes are implicated in an increased risk of hepatotoxicity caused by carbamazepine and valproic acid. This article summarizes the state of research on the effects of mutations of drug-metabolizing enzymes on the pharmacokinetics and pharmacodynamics of AED therapies. Future directions for the dose-adjustment of AED are discussed.

  3. Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.

    Science.gov (United States)

    Tolbert, Dwain; Bekersky, Ihor; Chu, Hui-May; Ette, Ene I

    2016-03-01

    A metabolic mechanism-based characterization of antiepileptic drug-drug interactions (DDIs) with clobazam in patients with Lennox-Gastaut syndrome (LGS) was performed using a population pharmacokinetic (PPK) approach. To characterize potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with LGS in study OV-1012 (NCT00518713) and 18 healthy participants in bioavailability study OV-1017 were pooled. Antiepileptic drugs (AEDs) were grouped based on their effects on the cytochrome P450 (CYP) isozymes responsible for the metabolism of clobazam and its metabolite, N-desmethylclobazam (N-CLB): CYP3A inducers (phenobarbital, phenytoin, and carbamazepine), CYP2C19 inducers (valproic acid, phenobarbital, phenytoin, and carbamazepine), or CYP2C19 inhibitors (felbamate, oxcarbazepine). CYP3A4 inducers-which did not affect the oral clearance of clobazam-significantly increased the formation of N-CLB by 9.4%, while CYP2C19 inducers significantly increased the apparent elimination rate of N-CLB by 10.5%, resulting in a negligible net change in the PK of the active metabolite. CYP2C19 inhibitors did not affect N-CLB elimination. Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobazam PK in this study, dosage adjustments may not be required for clobazam in the presence of the AEDs investigated here.

  4. Effect of topiramate and traditional antiepileptic drugs on pituitary-sexual gland axis in adult males with epilepsy

    Institute of Scientific and Technical Information of China (English)

    Fei Xu; Liang Yu; Jie Liu; Yongjie Luo; Hongbin Sun

    2007-01-01

    BACKGROUND: Some reports indicate that traditional antiepileptic drugs can cause a certain effect on reproductive endocrine system in epileptic patients. However, the effect of topiramate on reproductive endocrine system needs to be further studied.OBJECTIVE: To compare the effects of topiramate and traditional valproic acid and carbamazepine on pituitary-sexual gland axis in adult males with epilepsy.DESIGN: Self-contrast and randomly parallel controlled study.SETTING: Sichuan Academy of Medical Sciences (Department of Neurology, Sichuan Provincial People's Hospital).PARTICIPANTS: A total of 54 male epileptic patients aged from 18 to 75 years were selected from Department of Neurology, Sichuan Provincial People's Hospital from January 2004 to June 2006. All patients were diagnosed as epilepsy based on illness history and electroencephalogram (EEG), and types of epilepsy were classified based on the theory of epilepsy and epilepsy syndrome established by International Anti-epilepsy League in 1989 and 2001. The accepted patients and their relatives provided the confirmed consent.METHODS: ① The accepted patients were randomly divided into traditional treatment group [n =26,mean age of (34 ±14) years] and topiramate group [n =28, mean age of (28 ±17) years]. In addition, based on various kinds of drugs, patients in the traditional treatment group were divided into two subgroups,including carbamazepine group (n =14) and valproic acid group (n =12). Patients in both subgroups were respectively treated with carbamazepine (100 mg/table, Shanghai Sanwei Pharmaceutical Factory, batch number: 060705) and valproic acid (200 mg/table, Hunan Xiangzhong Pharmaceutical Co., Ltd., batch number: 061128). Patients in topiramate group were treated with topiramate (25 mg/table, Xi'an Yangsen Pharmaceutical Co., Ltd., batch number: 060215836). Administration: The beginning dosage of topiramate was 25 mg/d, and then increased 25 mg/d per week. The final dosage was 150 mg/d. In

  5. Behavior of selected pharmaceuticals in topsoil of Greyic Phaeozem

    Science.gov (United States)

    Kodesova, Radka; Klement, Ales; Kocarek, Martin; Fer, Miroslav; Golovko, Oksana; Grabic, Roman; Jaksik, Ondrej

    2014-05-01

    It has been documented in several studies that soil may be contaminated by human or veterinary pharmaceuticals. Some of pharmaceutical ingredient may be retained in soils. The rest can be transported to the surface and groundwater through surface runoff and infiltration. Mobility of contaminants in soils is dependent on many soil and pharmaceutical properties (e.g. pharmaceutical adsorption on soil particles and pharmaceutical degradation). The goals of this study were: (1) to measure adsorption isotherms of selected pharmaceuticals in one soil; (2) to evaluate degradation of selected pharmaceuticals in this soil, and (3) to evaluate impact of applied pharmaceuticals on biological activity in soil, which influences pharmaceutical decomposition. Batch sorption tests were performed for 7 selected pharmaceuticals (beta blockers Atenolol and Metoprolol, anticonvulsant Carbamazepin, and antibiotics Clarithromycin, Clindamycin, Trimetoprim and Sulfamethoxazol) and one soil (topsoil of Greyic Phaeozem from Čáslav). The same concentrations (0.5, 1, 2.5, 5 and 10 mg/l) were used for almost all pharmaceuticals except Clarithromycin (0.033, 0.08, 0.165, 0.25, 0.33 mg/l). The Freundlich equations were used to describe adsorption isotherms. Degradation of all 7 pharmaceuticals was also studied. Solutes of different pharmaceuticals (concentration of 8.3 mg/l) were added into the plastic bottles (one pharmaceutical per bottle) with soil. Concentrations of pharmaceuticals remaining in soil 1, 2, 5, 12, 23, 40 and 61 days after the pharmaceutical application were analyzed. Colony forming unites were evaluated to describe microbial activity in time affected by different pharmaceuticals. Adsorption of studied pharmaceuticals on soil particles decreasing as follows: Clarithromycin, Trimetoprim, Metoprolol, Clindamycin, Atenolol, Carbamazepin, Sulfamethoxazol. Degradation rates in some degree reflected adsorption of studied pharmaceuticals on soil particles and increased with

  6. Accumulation of pharmaceuticals, Enterococcus, and resistance genes in soils irrigated with wastewater for zero to 100 years in central Mexico.

    Directory of Open Access Journals (Sweden)

    Philipp Dalkmann

    Full Text Available Irrigation with wastewater releases pharmaceuticals, pathogenic bacteria, and resistance genes, but little is known about the accumulation of these contaminants in the environment when wastewater is applied for decades. We sampled a chronosequence of soils that were variously irrigated with wastewater from zero up to 100 years in the Mezquital Valley, Mexico, and investigated the accumulation of ciprofloxacin, enrofloxacin, sulfamethoxazole, trimethoprim, clarithromycin, carbamazepine, bezafibrate, naproxen, diclofenac, as well as the occurrence of Enterococcus spp., and sul and qnr resistance genes. Total concentrations of ciprofloxacin, sulfamethoxazole, and carbamazepine increased with irrigation duration reaching 95% of their upper limit of 1.4 µg/kg (ciprofloxacin, 4.3 µg/kg (sulfamethoxazole, and 5.4 µg/kg (carbamazepine in soils irrigated for 19-28 years. Accumulation was soil-type-specific, with largest accumulation rates in Leptosols and no time-trend in Vertisols. Acidic pharmaceuticals (diclofenac, naproxen, bezafibrate were not retained and thus did not accumulate in soils. We did not detect qnrA genes, but qnrS and qnrB genes were found in two of the irrigated soils. Relative concentrations of sul1 genes in irrigated soils were two orders of magnitude larger (3.15 × 10(-3 ± 0.22 × 10(-3 copies/16S rDNA than in non-irrigated soils (4.35 × 10(-5± 1.00 × 10(-5 copies/16S rDNA, while those of sul2 exceeded the ones in non-irrigated soils still by a factor of 22 (6.61 × 10(-4 ± 0.59 × 10(-4 versus 2.99 × 10(-5 ± 0.26 × 10(-5 copies/16S rDNA. Absolute numbers of sul genes continued to increase with prolonging irrigation together with Enterococcus spp. 23S rDNA and total 16S rDNA contents. Increasing total concentrations of antibiotics in soil are not accompanied by increasing relative abundances of resistance genes. Nevertheless, wastewater irrigation enlarges the absolute concentration of resistance genes in soils due to a

  7. Reconnaissance of Pharmaceutical Chemicals in Urban Streams of the Tualatin River Basin, Oregon, 2002

    Science.gov (United States)

    Rounds, Stewart A.; Doyle, Micelis C.; Edwards, Patrick M.; Furlong, Edward T.

    2009-01-01

    A reconnaissance of pharmaceutical chemicals in urban streams of the Tualatin River basin was conducted in July 2002 in an effort to better understand the occurrence and distribution of such compounds, and to determine whether they might be useful indicators of human-related stream contamination. Of the 21 pharmaceutical chemicals and metabolites tested, only 6 (acetaminophen, caffeine, carbamazepine, codeine, cotinine, and sulfamethoxazole) were detected in filtered stream samples from 10 sites. The concentrations of most of the detected compounds were relatively low (less than 0.05 microgram per liter). The most frequently detected compounds were cotinine (a nicotine metabolite, 8 of 10 samples) and caffeine (a stimulant, 7 of 10 samples). More compounds were detected in urban stream samples than in samples from forested or agricultural drainages. Filtered water samples also were collected from four locations within an advanced wastewater treatment facility to quantify the relative amounts of these chemicals in a municipal waste stream and to determine the degree to which those chemicals are removed by treatment processes. Fifteen pharmaceutical chemicals or metabolites were detected in wastewater treatment facility influent, with concentrations far exceeding those measured in streams. Only five of those compounds, however, were detected in the treated effluent (carbamazepine, cotinine, ibuprofen, metformin, and sulfamethoxazole) and most of those were at concentrations less than 0.2 microgram per liter. The target pharmaceutical chemicals and metabolites showed limited potential for use as tracers of specific types of human-related contamination in Tualatin River basin streams because of widespread sources (caffeine, for example) or extremely low concentrations. Caffeine and cotinine are likely to be good indicators of sources that can occur in urban areas, such as sewage spills or leaks or the widespread use and careless disposal of tobacco products and

  8. Research on transferring mechanism of pharmaceutically active compounds in urban sewage%PhACs在城市污水中迁移机理的研究

    Institute of Scientific and Technical Information of China (English)

    周海东; 王奉飞; 李涵

    2011-01-01

    以4种药理活性化合物(PhACs)为目标物,运用UPLC/MS为检测方法,针对其在城市污水处理厂工艺流程中的分布迁移进行了研究,并进一步实验研究了其迁移机理.所有PhACs在城市污水厂进出水中均被检出,进水中浓度为0.11μg/L(氯贝酸)-0.46μg/L(卡马西平),出水中50μg/L((氯贝酸)-0.45μg/L(卡马西平).卡马西平几乎不能被去除,除此之外,在生物处理阶段可较有效去除其它PhACs,其迁移机理主要是生物降解,生物降解速率与化合物种类及污泥类型有关.%Distribution and transportation of four pharmaceutically active compounds (PhACs) detected by upper performance liquid chromatography -mass spectrometry (UPLC/MS) was investigated in every unit of sewage treatment plants (STPs). Meanwhile, the mechanisms of transference of PhACs in the sewage were further experimented. All the target compounds were present in the influent and effluent sewages. The concentrations ranged from 0. 11 μg/L (clofibric acid) -0.46 μg/L (carbamazepine) in the influent sewages, and from 50 μg/L (clofibric acid) -0.45 μg/L (carbamazepine) in the effluent sewages. Except carbamazepine could be hardly removed in STPs, biological treatment stage seemed to be more effective to remove other PhACs from aqueous phase than primary treatment stage in STPs. The mechanism for their transference in the sewage was basically biodegradation, the rate of which was rerated to activated sludge type as well as compound property.

  9. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoeje River in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Bendz, David [Swedish Geotechnical Institute, Department of Environmental Technology, Hospitalsgatan 16A, S-211 33 Malmoe (Sweden)]. E-mail: David.Bendz@swedgeo.se; Paxeus, Nicklas A. [Gryaab, Karl IX:s vaeg, S-418 34 Gothenburg (Sweden); Ginn, Timothy R. [University of California, Department of Civil and Environmental Engineering, 1 Shields Avenue, 2001 Engineering III, Davis, CA 95616 (United States); Loge, Frank J. [University of California, Department of Civil and Environmental Engineering, 1 Shields Avenue, 2001 Engineering III, Davis, CA 95616 (United States)

    2005-07-15

    Pharmaceutically active compounds (PhACs) in the environment lately have been acknowledged to constitute a health risk for humans and terrestrial and aquatic ecosystems. Human and veterinary applications are the main sources of PhACs in the environment and the major pathways are excretion and discharge to the environment through sewage treatment plants (STPs). In this study, the occurrence and fate of selected human PhACs belonging to different therapeutic classes (non-steroidal anti-inflammatory drugs, lipid regulators, anti-epileptics, antibiotics and {beta}-blockers) were investigated in a small river in the very south of Sweden. The objectives of the study were to evaluate the impact of a high and rather constant load in sewage influent on downstream concentrations and whether substances that are metabolized to a high degree in humans also show a low persistency in a natural aquatic environment. Water samples were collected from the influent and effluent of the STP, in a series of dammed reservoirs leading to discharge into the Hoeje River in Sweden, and at several locations in the river downstream of the outfall. After enrichment by solid-phase extraction, the compounds were analyzed using GC-MS (methylated derivatives) or LC-MS/MS. In addition to the targeted pharmaceuticals, GC-MS analysis of the samples revealed the presence of other sewage-related pollutants (triclosan, caffeine, flame-retardants, antioxidants) and these results where included for comparison. Removal efficiencies were calculated in the STP and found to display a wide range with numerous species surviving treatment at greater than half their influent concentrations, including diclofenac, the anti-epileptic carbamazepine, a {beta}-blocker (propanolol), and antibiotics trimetoprim and sulfamethoxazole. Low removals were also observed for Tris(2-chloroisopropyl)phosphate (flame retardant), BHT-aldehyde (oxidation product of BHT) and synthetic musk (HHCB). The concentrations of chloride (Cl

  10. Small-fiber dysfunction in trigeminal neuralgia

    DEFF Research Database (Denmark)

    Cruccu, G.; Leandri, M.; Iannetti, G. D.

    2001-01-01

    Background: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information...... on small-afferent (nociceptive) function. Methods: The brain potentials evoked by CO2-laser pulses directed to the perioral and supraorbital regions were studied in 67 patients with idiopathic or symptomatic trigeminal neuralgia and 30 normal subjects. Of the 67 patients, 49 were receiving carbamazepine....... Results: All patients with symptomatic and 51% of those with idiopathic trigeminal neuralgia had frankly abnormal LEP on the painful side. The mean latency was significantly higher and mean amplitude lower on the painful than the nonpainful side. However, even on the nonpainful side, the mean latency...

  11. Forty-two Cases of Greater Occipital Neuralgia Treated by Acupuncture plus Acupoint-Injection

    Institute of Scientific and Technical Information of China (English)

    Pan Changqing; Tan Guangbo

    2008-01-01

    Objective:To observe the therapeutic effect of acupuncture plus acupoint-injection on greater occipital neuralgia.Methods:The 84 cases of greater occipital neuralgia were randomly divided into two groups,with 42 cases in the treatment group treated bv acupuncture plus acupoint-injection.and 42 cases in the control group treated with oral administration of carbamazepine.Results:The total effective rate was 92.8% in the treatment group and 71.4% in the control group.The difrerence in the tohal effective rate was significant (P<0.05)between the two groups.Conclusions:Acupuncture plus acupoint-injection is eriective for greater occipital neuralgia,better than the routine western medication.

  12. Homicide during postictal psychosis

    Directory of Open Access Journals (Sweden)

    Stephan Eisenschenk

    2014-01-01

    Full Text Available Postictal psychosis is characterized by a fluctuating combination of thought disorder, auditory and visual hallucinations, delusions, paranoia, affective change, and aggression including violent behavior. We present a case of homicide following a cluster of seizures. The patient's history and postictal behavior were his consistent with postictal psychosis. Contributing factors resulting in homicide may have included increased seizure frequency associated with a change in his AED regimen seizure frequency. The AED change to levetiracetam may also have increased impulsiveness with diminished mood regulation following discontinuation of carbamazepine. There is evidence that he had a cluster of seizures immediately prior to the murder which may have resulted in the postictal disinhibition of frontal lobe inhibitory systems. This homicide and other violent behaviors associated with postictal psychosis may be avoided with earlier recognition and treatment.

  13. [Suicidal poisoning with benzodiazepines].

    Science.gov (United States)

    Chodorowski, Z; Sein Anand, J

    1997-01-01

    In the period from 1987 to 1996, 103 patients with suicidal benzodiazepines poisoning were treated, including 62 women and 41 men from 16 to 79 (mean 34) years old. 23 persons were poisoned only by benzodiazepines, in 80 remaining cases intoxications were mixed eg. including benzodiazepines and alcohol, tricyclic antidepressants, barbiturates, opioids, phenothiazines. The main causes of suicides were mainly depression, drug addiction and alcoholism. Nobody died in the benzodiazepines group, while mortality rate in the group of mixed poisoning was 4%. Prescribing benzodiazepines by physicians was quite often not justified and facilitated, among others, accumulation of the dose sufficient for suicide attempt. Flumazenil was efficient for leading out from coma in 86% of cases with poisoning only by benzodiazepines and 13% of cases with mixed intoxications mainly containing benzodiazepines and alcohol or carbamazepine.

  14. Antiepleptic drug interactions: a clinical case demonstration.

    Science.gov (United States)

    Tesfaye, Hundie; Klapková, Eva; Tesfayeová, Alena; Komárek, Vladimír

    2011-01-01

    Epilepsy is a serious health disorder affecting both paediatric and adult population worldwide. Due to difficulties in identifying its aetiology, initial management is often guided by empiric therapy measures. Symptomatic control requires the use of antiepileptic drugs (AEDs), many of which have the potential for adverse drug interactions. Children are especially susceptible to drug interactions and frequently exhibit atypical adverse events, which may require special care. Aim. To demonstrate a case of a 15 year old girl suffering from refractory epilepsy with underlying focal cortical dysplasia (FCD), whose seizure deterioration was most probably associated with drug-drug interactions between prescribed common antiepileptic drugs, namely valproic acid, phenobarbital or the prodrug primidon and carbamazepine.

  15. Análise de fármacos em águas por SPE-UPLC-ESI-MS/MS

    Directory of Open Access Journals (Sweden)

    Vanessa de Jesus Gaffney

    2014-01-01

    Full Text Available A method was developed for the analysis of 31 pharmaceutical compounds in Lisbon's drinking water system, using solid-phase extraction (SPE and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS. The method was validated through estimation of the linearity range, method detection and quantification limits, matrix effects, precision and accuracy. The method detection and quantification limit ranges were 0.009-10 and 0.03-33 ng/L, respectively. Analytes were quantified in water samples collected from the EPAL (Empresa Portuguesa das Águas Livres S.A. supply system. Carbamazepine, atenolol, sulfadiazine, sulfamethazine, sulfapyridine, sulfamethoxazole, acetaminophen, caffeine and erythromycin were quantified in the analysed samples.

  16. Dichotic listening failure in dysphoric neuropsychiatric patients who endorse multiple seizure-like symptoms.

    Science.gov (United States)

    Springer, J A; Garvey, M J; Varney, N R; Roberts, R J

    1991-08-01

    In the present investigation, the dichotic word listening performance of a sample of 25 dysphoric neuropsychiatric patients who endorsed multiple partial seizure-like symptoms was compared with that of matched samples of normal controls and patients with mood disorders who did not endorse multiple seizure-like symptoms. Eighty percent of the patients who endorsed multiple episodic phenomena failed the dichotic listening task, compared with 8% of normal controls and 28% of patients with typical mood disorders. After treatment with carbamazepine, a subsample of polysymptomatic patients manifested significantly fewer seizure-like symptoms. This clinical improvement was typically associated with markedly improved dichotic listening performance in most cases. The results are consistent with our previous hypothesis that "subclinical" electrophysiological dysfunction may severely disrupt the normal transmission and processing of auditory information. Because it is sensitive to this type of presumed cerebral dysfunction and relatively specific, impaired dichotic listening performance is likely to be a useful clinical marker for this complex neuropsychiatric syndrome.

  17. Association between consistent purchase of anticonvulsants or lithium and suicide risk: a longitudinal cohort study from Denmark, 1995-2001

    DEFF Research Database (Denmark)

    Smith, Eric G; Søndergård, Lars; Lopez, Ana Garcia;

    2009-01-01

    BACKGROUND: Prior studies suggest anticonvulsants purchasers may be at greater risk of suicide than lithium purchasers. METHODS: Longitudinal, retrospective cohort study of all individuals in Denmark purchasing anticonvulsants (valproic acid, carbamazepine, oxcarbazepine or lamotrigine) (n=9952......) or lithium (n=6693) from 1995-2001 who also purchased antipsychotics at least once (to select out nonpsychiatric anticonvulsant use). Poisson regression of suicides by medication purchased (anticonvulsants or lithium) was conducted, controlling for age, sex, and calendar year. Confounding by indication...... was addressed by restricting the comparison to individuals prescribed the same medication: individuals with minimal medication exposure (e.g., who purchased only a single prescription of anticonvulsants) were compared to those individuals with more consistent medication exposure (i.e., purchasing > or = 6...

  18. Identification and management of alcohol withdrawal syndrome.

    Science.gov (United States)

    Mirijello, Antonio; D'Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2015-03-01

    Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and β-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed.

  19. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

    Science.gov (United States)

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-01-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities. PMID:27490534

  20. A Case with Bilateral Periventricular Nodular Heterotopia Diagnosed as Depression

    Directory of Open Access Journals (Sweden)

    Melek Kandemir

    2010-06-01

    Full Text Available Periventricular nodular heterotopia is a form of neuronal migration abnormality. Periventricular nodular heterotopia can easily be recognized by cranial magnetic resonance imaging. The most common clinical appearance is epileptic seizures. In some cases, symptoms are accompanied with psychiatric complaints. In this article, we report a 33-year-old female with complaints of left-sided paresthesia induced by emotional stress. She had been followed at an outpatient psychiatry clinic for about 10 years with the diagnosis of somatization disorder. Her electroencephalography recordings -awake as well as during sleep- were found to be normal. The cranial magnetic resonance imaging showed bilateral periventricular nodular heterotopia. Her seizures were controlled with carbamazepine treatment. Partial epileptic seizures might also be observed, even though the cerebral heterotopic lesions are bilateral. When a history is obtained from a patient with somatoform complaints, it should be kept in mind that these symptoms might be seizures, and the patient should be questioned accordingly.

  1. Determinants of Noncompliance to Clinic Appointments and Medications among Nigerian Children with Epilepsy: Experience in a Tertiary Health Facility in Enugu, Nigeria

    Directory of Open Access Journals (Sweden)

    Roland Chidi Ibekwe

    2016-01-01

    Full Text Available Purpose. To determine the frequency and determinants of noncompliance to clinic appointment and medication among Nigerian children with epilepsy. Method. This is a cross-sectional survey of noncompliance to clinic appointments and medication among 113 consecutive children with epilepsy attending the Paediatric Neurology Clinic of University of Nigeria Teaching Hospital, Enugu, southeastern Nigeria. Results. Noncompliance to clinic appointment and medication was 23% and 15.3%, respectively. The major reasons given were lack of finance, clashing with school time, and forgetting to take the drugs. Children whose mothers were less educated and unemployed were more likely to miss clinic appointments. Noncompliance to medication was associated with poor seizure control. Children that were on phenobarbitone were more likely to be noncompliant with medication than those on sodium valproate and/or carbamazepine. Conclusion. Missed clinic appointment and medication noncompliance are common among Nigerian children with epilepsy and financial constraint is the most common reason.

  2. Determinação simultânea de topiramato, carbamazepina, fenitoína e fenobarbital em plasma empregando cromatografia a gás com detector de nitrogênio e fósforo

    Directory of Open Access Journals (Sweden)

    Roberta Zilles Hahn

    2013-01-01

    Full Text Available Topiramate and the other frequently co-administered antiepileptic drugs carbamazepine, phenytoin and phenobarbital were determined in 100 µL plasma samples by gas chromatography with nitrogen phosphorus detection (GC-NPD, after a one-step liquid-liquid extraction with ethyl acetate, followed by flash methylation with trimethylphenylammonium hydroxide. Total chromatographic run time was 12.5 min. Intra-assay and inter-assay precision was 2.5-7.3% and 1.6-5.2%, respectively. Accuracy was 100.1-104.2%. The limit of quantitation was 1 µg mL-1 for all analytes, proving suitable for routine application in therapeutic drug monitoring of antiepileptic drugs.

  3. Ventricular tachycardia associated with lacosamide co-medication in drug-resistant epilepsy.

    Science.gov (United States)

    DeGiorgio, Andrew C; Desso, Tamara E; Lee, Lance; DeGiorgio, Christopher M

    2013-01-01

    We report a case of sustained ventricular tachycardia following the initiation of lacosamide as adjunctive epilepsy treatment. A 49-year-old male with intractable frontal lobe seizures experienced severe ventricular tachycardia following the addition of 400 mg lacosamide to his existing regimen of carbamazepine, lamotrigine, clonazepam, and valproate. The tachycardia occurred during a cardiac stress test; stress tests prior to initiation of lacosamide were normal. Conduction defects, including QRS prolongation, persisted during hospitalization until lacosamide was discontinued. The patient had no prior history of cardiac arrhythmia but did possess cardiac risk factors, including hypertension, hypercholesterolemia, and low heart rate variability. This case represents one part of a growing body of literature suggesting a link between arrhythmia and use of lacosamide, which enhances slow inactivation of sodium channels in both the brain and the heart. We believe further study may be necessary to assess the safety of lacosamide in epilepsy patients with cardiac risk factors.

  4. Teratogenic Potential of Antiepileptic Drugs in the Zebrafish Model

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    Sung Hak Lee

    2013-01-01

    Full Text Available The zebrafish model is an attractive candidate for screening of developmental toxicity during early drug development. Antiepileptic drugs (AEDs arouse concern for the risk of teratogenicity, but the data are limited. In this study, we evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ, ethosuximide (ETX, valproic acid (VPN, lamotrigine (LMT, lacosamide (LCM, levetiracetam (LVT, and topiramate (TPM in the zebrafish model. Zebrafish embryos were exposed to AEDs from initiation of gastrula (5.25 hours post-fertilization (hpf to termination of hatching (72 hpf which mimic the mammalian teratogenic experimental design. The lethality and teratogenic index (TI of AEDs were determined and the TI values of each drug were compared with the US FDA human pregnancy categories. Zebrafish model was useful screening model for teratogenic potential of antiepilepsy drugs and was in concordance with in vivo mammalian data and human clinical data.

  5. [Epilepsy pharmacogenetics : science or fiction?].

    Science.gov (United States)

    Depondt, Chantal

    2013-02-01

    Pharmacogenetics (PGX) is the study of how genetic variants influence individual responses to drugs. Although numerous candidate gene studies in epilepsy PGX have been published, to date only two validated associations exist: the association of the *2 and *3 alleles of CYP2C9 with phenytoin metabolism and the association of HLA-B*1502 with serious hypersensitivity reactions to carbamazepine. The advent of novel technologies such as genomewide association studies and next generation sequencing will likely lead to the identification of additional genetic biomarkers. The potential benefits of epilepsy PGX are multiple: epilepsy treatment in individual patients would become more rationalized, clinical trials could be stratified according to patients' genetic profiles and novel therapeutic pathways may be uncovered. Ultimately, it is hoped that PGX will improve the quality of life for people suffering from epilepsy worldwide.

  6. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy.

    Science.gov (United States)

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-06-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone and metronidazole for liver abscess had purpuric macules and papules on her extremities. One week later, she had generalized edema and skin rash with bullae and was diagnosed with concurrent linear IgA dermatosis and IgA nephropathy. After steroid treatment, the skin lesion subsided within two weeks, and kidney function slowly returned to normal. As both diseases occurred after a common possible cause, we predict their pathogeneses are associated.

  7. The impact of onsite wastewater disposal systems on groundwater in areas inundated by Hurricane Sandy in New York and New Jersey

    Science.gov (United States)

    Fisher, Irene; Phillips, Patrick; Colella, Kaitlyn; Fisher, Shawn C.; Tagliaferri, Tristen N.; Foreman, William; Furlong, Edward T.

    2016-01-01

    Coastal onsite wastewater disposal systems (OWDS) were inundated by Hurricane Sandy's storm tide. This study compares the shallow groundwater quality (nutrients, pharmaceuticals, and hormones) downgradient of OWDS before and after Hurricane Sandy, where available, and establishes a baseline for wastewater influence on groundwater in coastal communities inundated by Hurricane Sandy. Nutrients and contaminants of emerging concern (CECs) were detected in shallow groundwater downgradient of OWDS in two settings along the New Jersey and New York coastlines: 1) a single, centralized OWDS in a park; and 2) multiple OWDS (cesspools) in low-density residential and mixed-use/medium density residential areas. The most frequently detected pharmaceuticals were lidocaine (40%), carbamazepine (36%), and fexofenadine, bupropion, desvenlafaxine, meprobamate, and tramadol (24–32%). Increases in the number and total concentration of pharmaceuticals after Hurricane Sandy may reflect other factors (seasonality, usage) besides inundation, and demonstrate the importance of analyzing for a wide variety of CECs in regional studies.

  8. Anion-switchable supramolecular gels for controlling pharmaceutical crystal growth

    Science.gov (United States)

    Foster, Jonathan A.; Piepenbrock, Marc-Oliver M.; Lloyd, Gareth O.; Clarke, Nigel; Howard, Judith A. K.; Steed, Jonathan W.

    2010-12-01

    We describe the use of low-molecular-weight supramolecular gels as media for the growth of molecular crystals. Growth of a range of crystals of organic compounds, including pharmaceuticals, was achieved in bis(urea) gels. Low-molecular-weight supramolecular gelators allow access to an unlimited range of solvent systems, in contrast to conventional aqueous gels such as gelatin and agarose. A detailed study of carbamazepine crystal growth in four different bis(urea) gelators, including a metallogelator, is reported. The crystallization of a range of other drug substances, namely sparfloxacin, piroxicam, theophylline, caffeine, ibuprofen, acetaminophen (paracetamol), sulindac and indomethacin, was also achieved in supramolecular gel media without co-crystal formation. In many cases, crystals can be conveniently recovered from the gels by using supramolecular anion-triggered gel dissolution; however, crystals of substances that themselves bind to anions are dissolved by them. Overall, supramolecular gel-phase crystallization offers an extremely versatile new tool in pharmaceutical polymorph screening.

  9. Nanosuspension: An approach to enhance solubility of drugs

    Directory of Open Access Journals (Sweden)

    Vishal R Patel

    2011-01-01

    Full Text Available One of the major problems associated with poorly soluble drugs is very low bioavailability. The problem is even more complex for drugs like itraconazole, simvastatin, and carbamazepine which are poorly soluble in both aqueous and nonaqueous media, belonging to BCS class II as classified by biopharmaceutical classification system. Formulation as nanosuspension is an attractive and promising alternative to solve these problems. Nanosuspension consists of the pure poorly water-soluble drug without any matrix material suspended in dispersion. Preparation of nanosuspension is simple and applicable to all drugs which are water insoluble. A nanosuspension not only solves the problems of poor solubility and bioavailability, but also alters the pharmacokinetics of drug and thus improves drug safety and efficacy. This review article describes the preparation methods, characterization, and applications of the nanosuspension.

  10. Nanosuspension: An approach to enhance solubility of drugs.

    Science.gov (United States)

    Patel, Vishal R; Agrawal, Y K

    2011-04-01

    One of the major problems associated with poorly soluble drugs is very low bioavailability. The problem is even more complex for drugs like itraconazole, simvastatin, and carbamazepine which are poorly soluble in both aqueous and nonaqueous media, belonging to BCS class II as classified by biopharmaceutical classification system. Formulation as nanosuspension is an attractive and promising alternative to solve these problems. Nanosuspension consists of the pure poorly water-soluble drug without any matrix material suspended in dispersion. Preparation of nanosuspension is simple and applicable to all drugs which are water insoluble. A nanosuspension not only solves the problems of poor solubility and bioavailability, but also alters the pharmacokinetics of drug and thus improves drug safety and efficacy. This review article describes the preparation methods, characterization, and applications of the nanosuspension.

  11. Determinants of Noncompliance to Clinic Appointments and Medications among Nigerian Children with Epilepsy: Experience in a Tertiary Health Facility in Enugu, Nigeria

    Science.gov (United States)

    Ibekwe, Roland Chidi; Ndukuba, Appolos Chidi; Aronu, Ann Ebele; Eke, Christopher Bismarck; Ibekwe, MaryAnn Ugochi; Ojinnaka, Ngozi Chinyelu

    2016-01-01

    Purpose. To determine the frequency and determinants of noncompliance to clinic appointment and medication among Nigerian children with epilepsy. Method. This is a cross-sectional survey of noncompliance to clinic appointments and medication among 113 consecutive children with epilepsy attending the Paediatric Neurology Clinic of University of Nigeria Teaching Hospital, Enugu, southeastern Nigeria. Results. Noncompliance to clinic appointment and medication was 23% and 15.3%, respectively. The major reasons given were lack of finance, clashing with school time, and forgetting to take the drugs. Children whose mothers were less educated and unemployed were more likely to miss clinic appointments. Noncompliance to medication was associated with poor seizure control. Children that were on phenobarbitone were more likely to be noncompliant with medication than those on sodium valproate and/or carbamazepine. Conclusion. Missed clinic appointment and medication noncompliance are common among Nigerian children with epilepsy and financial constraint is the most common reason. PMID:26997756

  12. Parry-Romberg syndrome with hemimasticatory spasm in pregnancy; A dystonia mimic

    Directory of Open Access Journals (Sweden)

    Akhila Kumar Panda

    2014-01-01

    Full Text Available Parry-Romberg syndrome (PRS with hemimasticatory spasm (HMS is quite an uncommon overlapping phenomenon which very often mimics jaw closing dystonia. A previously healthy 35-year-old female, during her 5 th month of pregnancy started developing intermittent unilateral painful spasms of jaw while conversation, clinching of teeth, or eating, which led to frequent tongue bites. The spasms were worsened during pregnancy. She used to do certain manoeuvre like sensory tricks in form of touching involved side of the face to relieve the symptoms. Apart from this, she developed progressive hemifacial and hemitongue atrophy. Other medical and neurological examinations were normal. Laboratory investigations as well as neuroimaging were noncontributory. The spasm responded to carbamazepine but hemifacial atrophy persists. To our best knowledge, onset and worsening of this syndrome in pregnancy has not been described earlier which might be correlated either with some hormonal imbalance or some unknown mechanisms.

  13. Pharmaceutical Residues Affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike Wetlands

    DEFF Research Database (Denmark)

    Björklund, Erland; Svahn, Ola; Bak, Søren Alex

    2016-01-01

    plants (WWTPs). We analysed influent and treated wastewater, leachate water, lake, river, and wetland water alongside sediment for six model pharmaceuticals. The two WWTPs investigated released pharmaceutical residues at levels close to those previously observed in Swedish monitoring exercises. Compound......This study is the first to investigate the pharmaceutical burden from point sources affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike, Sweden. The investigated Biosphere Reserve is a >1000 km(2) wetland system with inflows from lakes, rivers, leachate from landfill, and wastewater-treatment......-dependent WWTP removal efficiencies ranging from 12 to 100 % for bendroflumethiazide, oxazepam, atenolol, carbamazepine, and diclofenac were observed. Surface-water concentrations in the most affected lake were ≥100 ng/L for the various pharmaceuticals with atenolol showing the highest levels (>300 ng...

  14. Identification of potential toxicity caused by O3 and ClO2 treatment of pharmaceuticals in wastewater

    DEFF Research Database (Denmark)

    Furuhagen, S. M.; Hörsing, Maritha; Ledin, Anna

    2011-01-01

    Chemical oxidation treatment is an effective innovative technology in wastewater treatment plants for removal of micro-pollutants in the effluent. In particular, ozonation (O3) and chlorine dioxide (ClO2) treatments are commonly used to degrade organic pollutants. By oxidation, the micro......-pollutants are generally transformed to compounds that are easier to degrade biologically. There is, however, a risk that the transformation products will have structures similar to the parent compound and still be biologically active. It has been shown, for example, that transformation products generated from...... Carbamazepine by chemical oxidation were more harmful to aquatic organisms compared to the parent compound. The aim of our study is to evaluate the potential risk of oxidation treatment, using O3 and ClO2, due to formation of toxic transformation products. The ecotoxicological effects caused by the two...

  15. [Erythromelalgia: Diagnosis and therapeutic approach].

    Science.gov (United States)

    Miranda, S; Le Besnerais, M; Langlois, V; Benhamou, Y; Lévesque, H

    2017-03-01

    Erythromelalgia is a rare intermittent vascular acrosyndrome characterized by the combination of recurrent burning pain, warmth and redness of the extremities. It is considered in its primary form as an autosomal dominant neuropathy related to mutations of SCN9A, the encoding gene of a voltage-gated sodium channel subtype Nav1.7. Secondary erythromelalgia is associated with myeloproliferative disorders, drugs (bromocriptine, calcium channel blockers), or clinical conditions such as rheumatic diseases or viral infection. Primary familial erythromelalgia include genetics and sporadic forms associated with small fibers neuropathy. Aspirin is a useful treatment of erythromelagia associated with myeloproliferative disorders. Treatment of primary erythromelalgia is difficult, individualized, with sodium channel blockers such as lidocaine, carbamazepine and mexiletine.

  16. Hemiconvulsion-hemiplegia-epilepsy syndrome: clinical course and neuroradiological features in a 20-month-old girl.

    Science.gov (United States)

    Bhat, Ramesh Y; Kakkar, Shruti; Prakashini, Koteshwara

    2014-03-10

    Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome involves initial sudden and prolonged unilateral convulsive seizures, followed by transient or permanent hemiplegia and epilepsy during infancy or early childhood. Seizures are prolonged, difficult to control and sometimes may require surgery. Hemiplegia varies in intensity, differs from Todd paralysis and disappears in about 20% of cases. Neuroimaging characteristically shows brain atrophy more pronounced on the hemisphere contralateral to the side of hemiplegia with dilation of the ventricular system. A 20-month-old girl presented with left hemiconvulsions and left hemiplegia lasting for a prolonged period. Seizures failed to resolve with various anticonvulsants even after many physician contacts. Characteristic neuroimaging findings, seizure control with carbamazepine and valproate, subsequent recovery of hemiplegia and attainment of developmental milestones observed on follow-up confirmed HHE syndrome. The case highlights the need for good seizure control in this syndrome.

  17. Antiepileptic drugs patterns in elderly inpatients in a Brazilian tertiary center, Salvador, Brazil

    Directory of Open Access Journals (Sweden)

    Telma Rocha de Assis

    2014-11-01

    Full Text Available Epilepsy is very prevalent among elderly inpatients and treatment is far from ideal. Objective To analyze prescribing patterns of antiepileptic drugs (AEDs for hospitalized elderly with epilepsy, their relations with comorbidities and comedications. Method We assessed prescription regimen of elderly patients that were under AED use for treatment of epileptic seizures, during hospitalization. One hundred and nine patients were enrolled. AED regimen was categorized into two groups: Group 1 defined as appropriate (carbamazepine, oxcarbazepine, valproic acid, gabapentin, clobazan and lamotrigine and Group 2 as inappropriate (phenytoin and phenobarbital. Results We found 73.4% of patients used inappropriate AEDs (p<0.001. Monotherapy was prescribed for 71.6% of patients. The most common comorbidity was hypertension. Potentially proconvulsant drugs as comedications were used for nearly half of patients. Conclusion Inappropriate AED therapy was commonly prescribed regimen for elderly inpatients. Some recommendations are discussed for a better care of elderly inpatients with epilepsy.

  18. [Topiramate: an experience in children with partial epilepsy].

    Science.gov (United States)

    Rocha, C; Brucki, S M

    2001-09-01

    Topiramate (TPM) is a new drug currently used in Brazil. We verified the clinical responses to TPM in children under 15 years-old. We started with 12.5 mg/day (1-7 mg/kg/day) and the doses increased 12,5 mg each week. Eleven children were studied, 9 females and 2 males, from 3 to 14 years-old with partial epilepsy associated to different etiological factors. Only one patient had an intense abdominal pain. The patients had weekly or daily seizures and after began TPM 1 patient stayed free from seizures, 5 improved more than 75% in frequency, 1 patient improved more than 50% and 3 had no control. A good control of seizures was achieved with a low dose of TPM as monotherapy and add-on therapy with carbamazepine even in severe cases.

  19. Polymeric Nanosuspensions for Enhanced Dissolution of Water Insoluble Drugs

    Directory of Open Access Journals (Sweden)

    Roya Yadollahi

    2013-01-01

    Full Text Available The aim of the present research is to formulate and evaluate polymeric nanosuspensions containing three model water insoluble drugs, nifedipine (NIF, carbamazepine (CBZ, and ibuprofen (IBU with various physicochemical properties. The nanosuspensions were prepared from hydroxypropyl methylcellulose (HPMC and polyvinylpyrrolidone (PVP by a cosolvent technique with polyethylene glycol (PEG-300 and water as the cosolvents. Physicochemical and morphological characteristics of the nanosuspensions (particle size, polydispersity index, and crystallinity have been correlated with the drug release behaviour. The effects of polymer, drug ratio on the physical, morphological, and dissolution characteristics of the drugs are reported. Drug release is significantly enhanced from the nanosuspensions; for example, the maximum NIF, IBU, and CBZ concentrations after 8-hour dissolution are increased approximately 37, 2, and 1.2 times, respectively, in comparison with the pure powdered drugs. Based on this solubilization enhancement performance, the nanosuspensions have potential for increasing the orally dosed bioavailability of NIF, IBU, and CBZ.

  20. The promise of psychiatric pharmacogenomics.

    Science.gov (United States)

    Hamilton, Steven P

    2015-01-01

    Clinicians already face "personalized" medicine every day while experiencing the great variation in toxicities and drug efficacy among individual patients. Pharmacogenetics studies are the platform for discovering the DNA determinants of variability in drug response and tolerability. Research now focuses on the genome after its beginning with analyses of single genes. Therapeutic outcomes from several psychotropic drugs have been weakly linked to specific genetic variants without independent replication. Drug side effects show stronger associations to genetic variants, including human leukocyte antigen loci with carbamazepine-induced dermatologic outcome and MC4R with atypical antipsychotic weight gain. Clinical implementation has proven challenging, with barriers including a lack of replicable prospective evidence for clinical utility required for altering medical care. More recent studies show promising approaches for reducing these barriers to routine incorporation of pharmacogenetics data into clinical care.

  1. Pharmacovigilance Programme of India: Recent developments and future perspectives

    Directory of Open Access Journals (Sweden)

    Vivekanandan Kalaiselvan

    2016-01-01

    Full Text Available Promoting safe use of medicines is a priority of Indian Pharmacopoeia Commission that functions as the National Coordination Center (NCC for Pharmacovigilance Programme of India (PvPI. One hundred and seventy-nine adverse drug reactions (ADRs monitoring centers currently report ADRs to NCC. Current India contribution to global safety database reaches 3% and the completeness score is 0.93 out of 1. NCC is taking several measures to enhance patient safety including capacity building for monitoring, surveillance, collaboration with national health programs and other organizations to increase ADR reporting and to ensure that PvPI is a vital knowledge database for Indian regulators. The Central Drugs Standard Control Organization has notified important safety label changes on drugs such as carbamazepine and piperacillin + tazobactam in the year 2015, other drugs are under monitoring for regulatory interventions.

  2. Isolated paroxysmal dysarthria caused by a single demyelinating midbrain lesion.

    Science.gov (United States)

    Codeluppi, Luca; Bigliardi, Guido; Chiari, Annalisa; Meletti, Stefano

    2013-10-16

    Paroxysmal dysarthria is an unusual condition characterised by brief episodes of dysarthria with the sudden onset and frequent recurrence. It has been mainly reported in multiple sclerosis and an association with midbrain lesions has been claimed; however, most of the reported patients had multiple brain alterations so it was difficult to associate this symptom with a specific lesion site. We illustrate the cases of two patients with an isolated demyelinating midbrain lesion presenting paroxysmal dysarthria as the only symptom; both participants had oligoclonal bands in the cerebrospinal fluid and an unremarkable follow-up. Both patients had benefit from carbamazepine treatment, similarly to previously reported cases. Our report confirms that a demyelinating midbrain lesion is sufficient to provoke paroxysmal dysarthria. It is noteworthy that an erroneous diagnosis of psychogenic disorders was initially made in both cases, highlighting the importance not to underestimate isolated paroxysmal symptoms in clinical practice.

  3. Removal of trace organic contaminants by a membrane bioreactor-granular activated carbon (MBR-GAC) system.

    Science.gov (United States)

    Nguyen, Luong N; Hai, Faisal I; Kang, Jinguo; Price, William E; Nghiem, Long D

    2012-06-01

    The removal of trace organics by a membrane bioreactor-granular activated carbon (MBR-GAC) integrated system were investigated. The results confirmed that MBR treatment can be effective for the removal of hydrophobic (log D>3.2) and readily biodegradable trace organics. The data also highlighted the limitation of MBR in removing hydrophilic and persistent compounds (e.g. carbamazepine, diclofenac, and fenoprop) and that GAC could complement MBR very well as a post-treatment process. The MBR-GAC system showed high removal of all selected trace organics including those that are hydrophilic and persistent to biological degradation at up to 406 bed volumes (BV). However, over an extended period, breakthrough of diclofenac was observed after 7320 BV. This suggests that strict monitoring should be applied over the lifetime of the GAC column to detect the breakthrough of hydrophilic and persistent compounds which have low removal by MBR treatment.

  4. Biodegradation of trace pharmaceutical substances in wastewater by a membrane bioreactor

    Institute of Scientific and Technical Information of China (English)

    Longli BO; Taro URASE; Xiaochang WANG

    2009-01-01

    The biodegradation of selected pharmaceutical micropollutants, including two pharmaceuticals with argued biodegradation, was studied by a lab-scale membrane bioreactor. The reaction kinetics and affecting factors were also investigated in this paper. Clofibric acid (CA) with contradictive biodegradation reported was degraded almost completely at different hydraulic retention times (HRTs) after adaptation to microorganisms. The biodegradation of CA was disturbed at low pH operation,while the activity of microorganisms recovered again after pH adjustment to neutral condition. Ibuprofen (IBP)degraded under neutral and acidic conditions. Removals of IBP and CA were zero-order and first-order reactions under high and low initial concentrations, respectively. Carbamazepine and diclofenac were not degraded regardless of HRTs and pH.

  5. Influence of chemical structure on skin reactions induced by antiepileptic drugs--the role of the aromatic ring.

    Science.gov (United States)

    Wang, Xiang-Qing; Shi, Xiao-Bing; Au, Ran; Chen, Fu-Shun; Wang, Fang; Lang, Sen-Yang

    2011-05-01

    Here we assessed whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain skin reaction. We found that 164 cases of skin reactions associated with the use of AEDs were reported. Aromatic AEDs were suspected in 88.41% (145/164) of patients with skin reactions versus 59.80% (2316/3873) of patients without skin reactions. The presence of an aromatic ring in the chemical structure was associated with a significant increased risk of skin reactions (adjusted ROR 3.50; 95% CI 2.29, 5.35). Among the aromatic AEDs, skin reactions were significantly associated with carbamazepine, lamotrigine, and oxarbazepine. These results confirm that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains AED-skin reactions. Skin reactions were reported triple as frequently with aromatic AEDs than with non-aromatic AEDs.

  6. Laser Raman spectroscopic analysis of polymorphic forms in microliter fluid volumes.

    Science.gov (United States)

    Anquetil, Patrick A; Brenan, Colin J H; Marcolli, Claudia; Hunter, Ian W

    2003-01-01

    Knowledge and control of the polymorphic phase of chemical compounds are important aspects of drug development in the pharmaceutical industry. We report herein in situ and real-time Raman spectroscopic polymorphic analysis of optically trapped microcrystals in a microliter volume format. The system studied in particular was the recrystallization of carbamazepine (CBZ) in methanol. Raman spectrometry enabled noninvasive measurement of the amount of dissolved CBZ in a sample as well as polymorphic characterization, whereas exclusive recrystallization of either CBZ form I or CBZ form III from saturated solutions was achieved by specific selection of sample cell cooling profiles. Additionally, using a microcell versus a macroscopic volume gives the advantage of reaching equilibrium much faster while using little compound quantity. We demonstrate that laser Raman spectral polymorphic analysis in a microliter cell is a potentially viable screening platform for polymorphic analysis and could lead to a new high throughput method for polymorph screening.

  7. Removal of emerging contaminants by simultaneous application of membrane ultrafiltration, activated carbon adsorption, and ultrasound irradiation.

    Science.gov (United States)

    Secondes, Mona Freda N; Naddeo, Vincenzo; Belgiorno, Vincenzo; Ballesteros, Florencio

    2014-01-15

    Advanced wastewater treatment is necessary to effectively remove emerging contaminants (ECs) with chronic toxicity, endocrine disrupting effects, and the capability to induce the proliferation of highly resistant microbial strains in the environment from before wastewater disposal or reuse. This paper investigates the efficiency of a novel hybrid process that applies membrane ultrafiltration, activated carbon adsorption, and ultrasound irradiation simultaneously to remove ECs. Diclofenac, carbamazepine, and amoxicillin are chosen for this investigation because of their assessed significant environmental risks. Removal mechanisms and enhancement effects are analysed in single and combined processes. The influence of adsorbent dose and ultrasonic frequency to EC removal are also investigated. Results suggest that adsorption is probably the main removal mechanism and is affected by the nature of ECs and the presence of other components in the mixture. Almost complete removals are achieved in the hybrid process for all ECs.

  8. Corrosion inhibitors from expired drugs.

    Science.gov (United States)

    Vaszilcsin, Nicolae; Ordodi, Valentin; Borza, Alexandra

    2012-07-15

    This paper presents a method of expired or unused drugs valorization as corrosion inhibitors for metals in various media. Cyclic voltammograms were drawn on platinum in order to assess the stability of pharmaceutically active substances from drugs at the metal-corrosive environment interface. Tafel slope method was used to determine corrosion rates of steel in the absence and presence of inhibitors. Expired Carbamazepine and Paracetamol tablets were used to obtain corrosion inhibitors. For the former, the corrosion inhibition of carbon steel in 0.1 mol L(-1) sulfuric acid solution was about 90%, whereas for the latter, the corrosion inhibition efficiency of the same material in the 0.25 mol L(-1) acetic acid-0.25 mol L(-1) sodium acetate buffer solution was about 85%.

  9. Aripiprazole in the acute and maintenance phase of bipolar I disorder

    Directory of Open Access Journals (Sweden)

    Zupancic M

    2012-01-01

    Full Text Available Melanie Zupancic1, Misty L Gonzalez2,31Southern Illinois University School of Medicine, 2Division of Medicine Psychiatry, Southern Illinois University School of Medicine, 3Southern Illinois University Edwardsville School of Pharmacy, Southern Illinois University Edwardsville, Springfield, IL, USAAbstract: Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second-generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents.Keywords: aripiprazole, bipolar disorder, acute treatment, maintenance treatment

  10. Management of adverse effects of mood stabilizers.

    Science.gov (United States)

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management.

  11. Eagle syndrome: case report.

    Science.gov (United States)

    Uludağ, İrem Fatma; Öcek, Levent; Zorlu, Yaşar; Uludağ, Burhanettin

    2013-01-01

    Eagle syndrome is an aggregate of symptoms caused by an elongated styloid process, most frequently resulting in headache, facial pain, dysphagia and sensation of foreign body in throat. The proper diagnosis is not difficult with clinical history, physical examination and radiographic assessment if there is a sufficient degree of suspicion. The treatment is very effective. We report here a typical case of Eagle syndrome which was misdiagnosed as trigeminal neuralgia for many years and was treated with carbamazepine. We aim to point the place of Eagle syndrome in the differential diagnosis of facial pain. We also re-emphasize the usefulness of the three-dimensional computed tomography in the diagnosis of Eagle syndrome. Even though Eagle syndrome is a rare condition, in cases of facial pain refractory to treatment or unexplained complaints of the head and neck region, it should be considered in the differential diagnosis as it has therapeutic consequences.

  12. Determinação simultânea de carbamazepina, fenitoína e fenobarbital em sangue seco em papel por cromatografia líquida de alta eficiência

    Directory of Open Access Journals (Sweden)

    Gabriela Martins Silva de Lima

    2014-07-01

    Full Text Available Carbamazepine, phenobarbital and phenytoin were determined in dried blood spots (DBS by high performance liquid chromatography, after extraction of 8 mm DBS using a mixture of acetonitrile and methanol. Analytes were separated by reversed-phase chromatography, with a run time of 17 minutes. Intra-assay and inter-assay precisions were in the 5.3 to 8.4% and 3.3 to 5.2% ranges, respectively. Accuracy was in the 98.8 to 104.3% range. The method had sensitivity to detect all analytes at levels below minimum therapeutic concentrations. The analytes were stable at 4 ºC and room temperature for up to 12 days and at 45 ºC for 9 days. The method was applied to 14 paired clinical samples of blood serum and DBS.

  13. [Treatment of pediatric epilepsy].

    Science.gov (United States)

    Ito, Susumu; Oguni, Hirokazu

    2014-05-01

    Recently, the treatment strategy for pediatric epilepsy has been dramatically changed in Japan, because of the approval of new-generation antiepileptic drugs. Since 2006, a total of 6 new antiepileptic drugs, including gabapentin (GBP; adults/pediatric patients: 2006/2011 [year of approval]), topiramate (TPM; 2007/2013), lamotrigine (LTG; 2008/2008), levetiracetam (LEV; 2010/2013), stiripentol (STP; 2012/2012), and rufinamide (RUF; 2013/2013), have been introduced. Thus far, valproate (VPA) and carbamazepine (CBZ) have been first indicated for "generalized" epilepsy and "focal" epilepsy syndromes/types, respectively, in Japan. However, the approval of these new drugs could allow us to choose more effective and less toxic ones at an early stage of treatment. In this chapter, we describe the latest domestic and foreign guidelines for the treatment of pediatric epilepsy.

  14. [Malignant lymphoma in a perineural spreading along trigeminal nerve, which developed as trigeminal neuralgia].

    Science.gov (United States)

    Mano, Tomoo; Matsuo, Koji; Kobayashi, Yosuke; Kobayashi, Yasushi; Ozawa, Hiroaki; Arakawa, Toshinao

    2014-01-01

    A rare cause of trigeminal neuralgia is malignant lymphoma which spread along the trigeminal nerve. We report a 79-year-old male presented with 4-month history of neuralgic pain in right cheek. He was diagnosed as classical trigeminal neuralgia. It had improved through medication of carbamazepine. Four months later, the dull pain unlike neuralgia complicated on the right cheeks, it was ineffective with the medication. Furthermore, diplopia and facial palsy as the other cranial nerve symptoms appeared. Gadolinium-enhanced magnetic resonance imaging (MRI) revealed contrast-enhanced mass lesion extend both external pterygoid muscle and brainstem through the swelling trigeminal nerve. The patient was pathological diagnosed of diffuse large B cell lymphoma by biopsy. Malignant lymphoma should be considered in the different diagnosis of cases with a minimal single cranial nerve symptom.

  15. Update on neuropathic pain treatment for trigeminal neuralgia. The pharmacological and surgical options.

    Science.gov (United States)

    Al-Quliti, Khalid W

    2015-04-01

    Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial pain, originating from the trigeminal nerve. Careful history of typical symptoms is crucial for diagnosis. Most cases are caused by vascular compression of the trigeminal root adjacent to the pons leading to focal demyelination and ephaptic axonal transmission. Brain imaging is required to exclude secondary causes. Many medical and surgical treatments are available. Most patients respond well to pharmacotherapy; carbamazepine and oxcarbazepine are first line therapy, while lamotrigine and baclofen are considered second line treatments. Other drugs such as topiramate, levetiracetam, gabapentin, pregabalin, and botulinum toxin-A are alternative treatments. Surgical options are available if medications are no longer effective or tolerated. Microvascular decompression, gamma knife radiosurgery, and percutaneous rhizotomies are most promising surgical alternatives. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on available evidence and guidelines.

  16. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

    Science.gov (United States)

    Fan, Hueng-Chuen; Lee, Herng-Shen; Chang, Kai-Ping; Lee, Yi-Yen; Lai, Hsin-Chuan; Hung, Pi-Lien; Lee, Hsiu-Fen; Chi, Ching-Shiang

    2016-08-01

    Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

  17. MRI 3D CISS– A Novel Imaging Modality in Diagnosing Trigeminal Neuralgia – A Review

    Science.gov (United States)

    Besta, Radhika; Shankar, Y. Uday; Kumar, Ashwini; Prakash, S. Bhanu

    2016-01-01

    Trigeminal Neuralgia (TN) is considered as one of the most painful neurologic disorders affecting oro-facial region. TN is often diagnosed clinically based on the patients complete history of pain (severity, duration, episodes etc), relief of pain on test dose of Carbamazepine, regional block of long acting anaesthetic. However, Magnetic Resonance Imaging (MRI) plays an important and confirmatory role in showing Neuro Vascular Conflict (NVC) which is the commonest causative factor for TN. This article reviews the effectiveness of three-dimensional constructive interference in steady-state (3D-CISS) MRI in diagnosing the exact location, degree of neurovascular conflict responsible for classical as well as atypical TN and possible pre-treatment evaluation and treatment outcome. PMID:27135019

  18. Teratogenic potential of antiepileptic drugs in the zebrafish model.

    Science.gov (United States)

    Lee, Sung Hak; Kang, Jung Won; Lin, Tao; Lee, Jae Eun; Jin, Dong Il

    2013-01-01

    The zebrafish model is an attractive candidate for screening of developmental toxicity during early drug development. Antiepileptic drugs (AEDs) arouse concern for the risk of teratogenicity, but the data are limited. In this study, we evaluated the teratogenic potential of seven AEDs (carbamazepine (CBZ), ethosuximide (ETX), valproic acid (VPN), lamotrigine (LMT), lacosamide (LCM), levetiracetam (LVT), and topiramate (TPM)) in the zebrafish model. Zebrafish embryos were exposed to AEDs from initiation of gastrula (5.25 hours post-fertilization (hpf)) to termination of hatching (72 hpf) which mimic the mammalian teratogenic experimental design. The lethality and teratogenic index (TI) of AEDs were determined and the TI values of each drug were compared with the US FDA human pregnancy categories. Zebrafish model was useful screening model for teratogenic potential of antiepilepsy drugs and was in concordance with in vivo mammalian data and human clinical data.

  19. Choking at Night: A Case of Opercular Nocturnal Frontal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Geetanjali Rathore

    2013-01-01

    Full Text Available Frontal lobe seizures have a tendency to occur in sleep and in most cases occur exclusively insleep; these individuals are said to have nocturnal frontal lobe (NFLE. NFLE can be difficult to distinguish clinically from various other sleep disorders, particularly parasomnias, which also present with paroxysmal motor activity in sleep. Interictal and ictal EEG findings are frequently unremarkable or nonspecific in both parasomnias and NFLE making the diagnosis even more difficult. Nocturnal epilepsy should be suspected in patients with paroxysmal events at night characterized by high frequency, repetition, extrapyramidal features, and marked stereotypy of attacks. Here we present a 13-year-old female who was extensively worked up for choking episodes at night. On repeat video EEG she was found to have frontal opercular seizures. Once on Carbamazepine, her seizures completely resolved.

  20. Pharmaceuticals as indicators of anthropogenic influence on the groundwater of Ljubljansko polje and Ljubljansko barje aquifers

    Directory of Open Access Journals (Sweden)

    Karin Lah

    2009-12-01

    Full Text Available The attention of numerous researches has been recently focused on the determination of pharmaceuticals and other persistent chemicals in the environment. The substances enter groundwater either thorough direct discharge or indirectly (through surface or waste water. Pharmaceuticals in groundwater can be regarded as artificial tracers that enable the evaluation of general anthropogenic influence on the environment and identification of the most vulnerable areas of aquifers.The article presents the properties of distribution of caffeine, carbamazepine and propyphenazone in the area of Ljubljansko polje and Ljubljansko barje. Ljubljansko polje and Barje are important drinking water resources. These pollutants are indicators of sewage system efficiency,however,in urban areas without sewage they indicate the aquifer’s ability of natural attenuation.

  1. Use of psychotropic drugs during pregnancy and breast-feeding

    DEFF Research Database (Denmark)

    Larsen, E R; Damkier, P; Pedersen, L H

    2015-01-01

    OBJECTIVE: To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. METHOD: As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women...... with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. RESULTS...... and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. CONCLUSION: It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how...

  2. A influência da piperina na biodisponibilidade de fármacos: uma abordagem molecular

    Directory of Open Access Journals (Sweden)

    Ramon G. de Oliveira

    2014-01-01

    Full Text Available Piperine is the major alkaloid of Piper nigrum Linn., used as a spice and in folk medicine. We present a molecular docking study supporting experimental data on the enhancement in bioavailability of propranolol, theophylline, phenytoin, nevirapine, nimesulide, pyrazinamide, carbamazepine, and spartein in the presence of piperine. The complex formed with piperine and CYP3A4 was shown to be the most stable of all, with a binding energy of -8.60 kcal/mol. This explains the related mechanism of drug-herb interaction, since the better anchoring of piperine in the active site of CYP3A4 can hinder the drug-enzyme interaction, thereby increasing the bioavailability of the drugs studied.

  3. Quantitative structure property relationships for the adsorption of pharmaceuticals onto activated carbon.

    Science.gov (United States)

    Dickenson, E R V; Drewes, J E

    2010-01-01

    Isotherms were determined for the adsorption of five pharmaceutical residues, primidone, carbamazepine, ibuprofen, naproxen and diclofenac, to Calgon Filtrasorb 300 powdered activated carbon (PAC). The sorption behavior was examined in ultra-pure and wastewater effluent organic matter (EfOM) matrices, where more sorption was observed in the ultra-pure water for PAC doses greater than 10 mg/L suggesting the presence of EfOM hinders the sorption of the pharmaceuticals to the PAC. Adsorption behaviors were described by the Freundlich isotherm model. Quantitative structure property relationships (QSPRs) in the form of polyparameter linear solvation energy relationships were developed for simulating the Freundlich adsorption capacity in both ultra-pure and EfOM matrices. The significant 3D-based descriptors for the QSPRs were the molar volume, polarizability and hydrogen-bond donor parameters.

  4. Neurogenic muscle cramps.

    Science.gov (United States)

    Katzberg, Hans D

    2015-08-01

    Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment.

  5. Epilepsy and music: practical notes.

    Science.gov (United States)

    Maguire, M

    2017-04-01

    Music processing occurs via a complex network of activity far beyond the auditory cortices. This network may become sensitised to music or may be recruited as part of a temporal lobe seizure, manifesting as either musicogenic epilepsy or ictal musical phenomena. The idea that sound waves may directly affect brain waves has led researchers to explore music as therapy for epilepsy. There is limited and low quality evidence of an antiepileptic effect with the Mozart Sonata K.448. We do not have a pathophysiological explanation for the apparent dichotomous effect of music on seizures. However, clinicians should consider musicality when treating patients with antiepileptic medication or preparing patients for epilepsy surgery. Carbamazepine and oxcarbazepine each may cause a reversible altered appreciation of pitch. Surgical cohort studies suggest that musical memory and perception may be affected, particularly following right temporal lobe surgery, and discussion of this risk should form part of presurgical counselling.

  6. Compulsive gambling possibly associated with antiepileptic medication

    Directory of Open Access Journals (Sweden)

    Susanne Storrier

    2014-01-01

    Full Text Available Compulsive gambling is recognized with Parkinson's disease treatment with dopamine agonists but has not been reported with antiepileptic medications (AEMs in epilepsy. This is the first report regarding possible compulsive gambling, provoked by AEMs in a patient with idiopathic generalized epilepsy, who presented with nonconvulsive status epilepticus, having previously not achieved seizure control with carbamazepine, valproate, (VPA, topiramate, gabapentin (GPT, lamotrigine (LTG, and clobazam. Levetiracetam (LEV was added to VPA and GPT, which the patient was already taking and LTG subsequently retrialed. Following the reintroduction of LTG, she lost $4000–5000, which she concealed. With better seizure control, VPA and GPT were withdrawn, leaving her on LEV and LTG. With increased LTG dosage, she lost $50,000, prompting discovery of her gambling.

  7. Anticonvulsant hypersensitivity syndrome to lamotrigine confirmed by lymphocyte stimulation in vitro

    Directory of Open Access Journals (Sweden)

    Karande Sunil

    2006-02-01

    Full Text Available Anticonvulsant hypersensitivity syndrome (AHS developing to lamotrigine, a non-aromatic anticonvulsant, has rarely been reported. We present a two-year-old boy with refractory epilepsy on valproic acid and lamotrigine therapy who developed fever and a maculopapular itchy rash. Blood investigations detected lymphocytosis and thrombocytopenia. With a presumptive diagnosis of AHS, lamotrigine was discontinued. The fever and rash resolved over the next three days and the child was discharged on valproic acid and clobazam. The diagnosis was confirmed by in vitro lymphocyte toxicity assay, which not only demonstrated increased cell death following exposure to lamotrigine, but also to the three first-line aromatic anticonvulsants: phenytoin, phenobarbital and carbamazepine. The potential of first-line aromatic anticonvulsants to cause AHS should be remembered in a patient who has developed AHS on exposure to lamotrigine. Timely recognition of this rare but potentially fatal drug reaction is important.

  8. Amino acids as co-amorphous stabilizers for poorly water soluble drugs--Part 1

    DEFF Research Database (Denmark)

    Löbmann, Korbinian; Grohganz, Holger; Laitinen, Riikka

    2013-01-01

    . However, this strategy only led to a small number of marketed products usually because of inadequate physical stability of the drug (crystallization). In this study, we investigated a fundamentally different approach to stabilize the amorphous form of drugs, namely the use of amino acids as small...... molecular weight excipients that form specific molecular interactions with the drug resulting in co-amorphous forms. The two poorly water soluble drugs carbamazepine and indomethacin were combined with amino acids from the binding sites of the biological receptors of these drugs. Mixtures of drug...... and the amino acids arginine, phenylalanine, tryptophan and tyrosine were prepared by vibrational ball milling. Solid-state characterization with X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed that the various blends could be prepared as homogeneous, single phase co...

  9. Gelastic epilepsy: Beyond hypothalamic hamartomas

    Directory of Open Access Journals (Sweden)

    Reinaldo Uribe-San-Martin

    2015-01-01

    Full Text Available Gelastic epilepsy or laughing seizures have been historically related to children with hypothalamic hamartomas. We report three adult patients who had gelastic epilepsy, defined as the presence of seizures with a prominent laugh component, including brain imaging, surface/invasive electroencephalography, positron emission tomography, and medical/surgical outcomes. None of the patients had hamartoma or other hypothalamic lesion. Two patients were classified as having refractory epilepsy (one had biopsy-proven neurocysticercosis and the other one hippocampal sclerosis and temporal cortical dysplasia. The third patient had no lesion on MRI and had complete control with carbamazepine. Both lesional patients underwent resective surgery, one with complete seizure control and the other one with poor outcome. Although hypothalamic hamartomas should always be ruled out in patients with gelastic epilepsy, laughing seizures can also arise from frontal and temporal lobe foci, which can be surgically removed. In addition, we present the first case of gelastic epilepsy due to neurocysticercosis.

  10. Familial recurrent hypersomnia: two siblings with Kleine-Levin syndrome and menstrual-related hypersomnia.

    Science.gov (United States)

    Rocamora, Rodrigo; Gil-Nagel, Antonio; Franch, Oriol; Vela-Bueno, Antonio

    2010-11-01

    Kleine-Levin syndrome and menstrual-related hypersomnia are rare idiopathic sleep disorders occurring primarily in adolescence. They are characterized by intermittent periods of excessive sleepiness, cognitive disturbances, and behavioral abnormalities. In both, the etiology remains unknown but autoinmune, hormonal, infectious, and inflammatory mechanisms have been proposed. The authors describe, for the first time, the association of Kleine-Levin syndrome and menstrual-related hypersomnia in 2 adolescent siblings who shared the human leukocyte antigen (HLA) loci DQB1*0501. The same haplotype has been associated with sleepwalking and with rapid eye movement (REM) sleep behavior disorder. This gender differences in the manifestation of a probably genetic influenced sleep disorder suggests that hormonal mechanisms could be implicated in the phenotypical expression of this sleep disorder. The male sibling with Kleine-Levin syndrome was easily controlled with carbamazepine in low doses, but his sister could be only efficaciously treated with oral contraceptives.

  11. Delusional Disorder in a Patient with Corpus Callosum Agenesis

    Science.gov (United States)

    Saha, Rashmita; Doval, Nimisha

    2016-01-01

    Agenesis of corpus callosum is rare and associated neuropsychiatric abnormalities reported are epilepsy, Asperger’s syndrome, learning problems, depression, schizophrenia, conduct disorder and conversion symptoms. Schizophrenia is the most common psychiatric disorder reported among corpus callosum agenesis. We report a rare case of delusional disorder with corpus callosum agenesis and seizure disorder. The patient presented with delusions of persecution towards younger brother and mother, disturbed sleep and reduced appetite. She had a history of seizure disorder of ten years duration, which was controlled with carbamazepine and levetiracetam. Neurological examination was normal. On MRI, corpus callosum agenesis was detected. She was put on an atypical antipsychotic quetiapine to which her psychiatric symptoms responded completely. PMID:28208982

  12. Photocatalytic degradation of contaminants of concern with composite NF-TiO2 films under visible and solar light.

    Science.gov (United States)

    Barndõk, H; Peláez, M; Han, C; Platten, W E; Campo, P; Hermosilla, D; Blanco, A; Dionysiou, D D

    2013-06-01

    This study reports the synthesis and characterization of composite nitrogen and fluorine co-doped titanium dioxide (NF-TiO(2)) for the removal of contaminants of concern in wastewater under visible and solar light. Monodisperse anatase TiO(2) nanoparticles of different sizes and Evonik P25 were assembled to immobilized NF-TiO(2) by direct incorporation into the sol-gel or by the layer-by-layer technique. The composite films were characterized with X-ray diffraction, high-resolution transmission electron microscopy, environmental scanning electron microscopy, and porosimetry analysis. The photocatalytic degradation of atrazine, carbamazepine, and caffeine was evaluated in a synthetic water solution and in an effluent from a hybrid biological concentrator reactor (BCR). Minor aggregation and improved distribution of monodisperse titania particles was obtained with NF-TiO(2)-monodisperse (10 and 50 nm) from the layer-by-layer technique than with NF-TiO(2) +monodisperse TiO(2) (300 nm) directly incorporated into the sol. The photocatalysts synthesized with the layer-by-layer method achieved significantly higher degradation rates in contrast with NF-TiO(2)-monodisperse titania (300 nm) and slightly faster values when compared with NF-TiO(2)-P25. Using NF-TiO(2) layer-by-layer with monodisperse TiO(2) (50 nm) under solar light irradiation, the respective degradation rates in synthetic water and BCR effluent were 14.6 and 9.5 × 10(-3) min(-1) for caffeine, 12.5 and 9.0 × 10(-3) min(-1) for carbamazepine, and 10.9 and 5.8 × 10(-3) min(-1) for atrazine. These results suggest that the layer-by-layer technique is a promising method for the synthesis of composite TiO(2)-based films compared to the direct addition of nanoparticles into the sol.

  13. Groundwater quality impacts from the land application of treated municipal wastewater in a large karstic spring basin: Chemical and microbiological indicators

    Science.gov (United States)

    Katz, B.G.; Griffin, Dale W.; Davis, J.H.

    2009-01-01

    Geochemical and microbiological techniques were used to assess water-quality impacts from the land application of treated municipal wastewater in the karstic Wakulla Springs basin in northern Florida. Nitrate-N concentrations have increased from about 0.2 to as high as 1.1??mg/L (milligrams per liter) during the past 30??years in Wakulla Springs, a regional discharge point for groundwater (mean flow about 11.3??m3/s) from the Upper Floridan aquifer (UFA). A major source of nitrate to the UFA is the approximately 64??million L/d (liters per day) of treated municipal wastewater applied at a 774??ha (hectare) sprayfield farming operation. About 260 chemical and microbiological indicators were analyzed in water samples from the sprayfield effluent reservoir, wells upgradient from the sprayfield, and from 21 downgradient wells and springs to assess the movement of contaminants into the UFA. Concentrations of nitrate-N, boron, chloride, were elevated in water samples from the sprayfield effluent reservoir and in monitoring wells at the sprayfield boundary. Mixing of sprayfield effluent water was indicated by a systematic decrease in concentrations of these constituents with distance downgradient from the sprayfield, with about a 10-fold dilution at Wakulla Springs, about 15??km (kilometers) downgradient from the sprayfield. Groundwater with elevated chloride and boron concentrations in wells downgradient from the sprayfield and in Wakulla Springs had similar nitrate isotopic signatures, whereas the nitrate isotopic composition of water from other sites was consistent with inorganic fertilizers or denitrification. The sprayfield operation was highly effective in removing most studied organic wastewater and pharmaceutical compounds and microbial indicators. Carbamazepine (an anti-convulsant drug) was the only pharmaceutical compound detected in groundwater from two sprayfield monitoring wells (1-2??ppt). One other detection of carbamazepine was found in a distant well

  14. Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.

    Science.gov (United States)

    Sarro, Giovambattista De; Paola, Eugenio Donato Di; Gratteri, Santo; Gareri, Pietro; Rispoli, Vincenzo; Siniscalchi, Antonio; Tripepi, Giovanni; Gallelli, Luca; Citraro, Rita; Russo, Emilio

    2012-03-01

    The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

  15. 直流电普鲁卡因离子导入治疗带状疱疹后遗神经痛的临床观察%The clinical observation of Dc procaine iontophoresis in the treatment of postherpetic neuralgia

    Institute of Scientific and Technical Information of China (English)

    肖展翅; 方丽萍; 刘秋梅; 李钢; 甘小莉; 陈洪汉

    2014-01-01

    Objective To investigate the efficacy , physical therapy and drug adverse reactions of Dc procaine iontophoresis in the treatment of postherpetic neuralgia .Methods Forty-eight postherpetic neuralgia patients were randomly divided into two groups .The control group take carbamazepine and mecobalamine orally in 23 cases ,the treatment group take carbamazepine and mecobalamine orally plus Dc procaine iontophoresis in 25 cases. Pain scores measured by numerical rating scale between the two groups before and after the treatment .Results The efficacy in treatment group was better than that in control group ,and the adverse reactions were mild .Conclusion Dc procaine iontophoresis is an effective treatment to relieve the postherpetic neuralgia , it is secure and efficient to improve the quality of life .%目的:观察直流电普鲁卡因离子导入治疗带状疱疹后遗神经痛( PHN)的疗效,以及理疗和药物的不良反应。方法48例PHN患者随机分成两组,对照组23例,给予口服卡马西平、甲钴胺;治疗组25例,在口服卡马西平、甲钴胺的同时,原发疱疹部位作直流电普鲁卡因离子导入治疗。采用国际通用数字评价量表对两组治疗前后疼痛评分对比。结果治疗组疗效优于对照组,不良反应轻微。结论直流电普鲁卡因离子导入治疗能有效减轻PHN症状,改善患者生活质量,安全有效。

  16. Impact of sludge stabilization processes and sludge origin (urban or hospital) on the mobility of pharmaceutical compounds following sludge landspreading in laboratory soil-column experiments.

    Science.gov (United States)

    Lachassagne, Delphine; Soubrand, Marilyne; Casellas, Magali; Gonzalez-Ospina, Adriana; Dagot, Christophe

    2015-11-01

    This study aimed to determine the effect of sludge stabilization treatments (liming and anaerobic digestion) on the mobility of different pharmaceutical compounds in soil amended by landspreading of treated sludge from different sources (urban and hospital). The sorption and desorption potential of the following pharmaceutical compounds: carbamazepine (CBZ), ciprofloxacin (CIP), sulfamethoxazole (SMX), salicylic acid (SAL), ibuprofen (IBU), paracetamol (PAR), diclofenac (DIC), ketoprofen (KTP), econazole (ECZ), atenolol (ATN), and their solid-liquid distribution during sludge treatment (from thickening to stabilization) were investigated in the course of batch testing. The different sludge samples were then landspread at laboratory scale and leached with an artificial rain simulating 1 year of precipitation adapted to the surface area of the soil column used. The quality of the resulting leachate was investigated. Results showed that ibuprofen had the highest desorption potential for limed and digested urban and hospital sludge. Ibuprofen, salicylic acid, diclofenac, and paracetamol were the only compounds found in amended soil leachates. Moreover, the leaching potential of these compounds and therefore the risk of groundwater contamination depend mainly on the origin of the sludge because ibuprofen and diclofenac were present in the leachates of soils amended with urban sludge, whereas paracetamol and salicylic acid were found only in the leachates of soils amended with hospital sludge. Although carbamazepine, ciprofloxacin, sulfamethoxazole, ketoprofen, econazole, and atenolol were detected in some sludge, they were not present in any leachate. This reflects either an accumulation and/or (bio)degradation of these compounds (CBZ, CIP, SMX, KTP, ECZ, and ATN ), thus resulting in very low mobility in soil. Ecotoxicological risk assessment, evaluated by calculating the risk quotients for each studied pharmaceutical compound, revealed no high risk due to the

  17. Occurrence and seasonal variations of 25 pharmaceutical residues in wastewater and drinking water treatment plants.

    Science.gov (United States)

    Kot-Wasik, A; Jakimska, A; Śliwka-Kaszyńska, M

    2016-12-01

    Thousands of tons of pharmaceuticals are introduced into the aqueous environment due to their incomplete elimination during treatment process in wastewater treatment plants (WWTPs) and water treatment plants (WTPs). The presence of pharmacologically active compounds in the environment is of a great interest because of their potential to cause negative effects. Furthermore, drugs can undergo different processes leading to the formation of new transformation products, which may be more toxic than the parent compound. In light of these concerns, within the research a new, rapid and sensitive analytical procedure for the determination of a wide range of pharmaceuticals from different classes using solid phase extraction (SPE) and high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) technique in different water samples was developed. This methodology was applied to investigate the occurrence, removal efficiency of 25 pharmaceuticals during wastewater and drinking water treatment, and seasonal variability in the amount of selected pharmaceuticals in WWTP and WTP over a year. The most often detected analytes in water samples were carbamazepine (100 % of samples) and ibuprofen (98 % of samples), concluding that they may be considered as pollution indicators of the aqueous environment in tested area. Highly polar compound, metformin, was determined at very high concentration level of up to 8100 ng/L in analyzed water samples. Drugs concentrations were much higher in winter season, especially for non-steroidal inflammatory drugs (NSAIDs) and caffeine, probably due to the inhibited degradation related to lower temperatures and limited sunlight. Carbamazepine was found to be the most resistant drug to environmental degradation and its concentrations were at similar levels during four seasons.

  18. Drug resistance in cortical and hippocampal slices from resected tissue of epilepsy patients: no significant impact of P-glycoprotein and Multidrug resistance associated proteins.

    Directory of Open Access Journals (Sweden)

    Nora eSandow

    2015-02-01

    Full Text Available Drug resistant patients undergoing epilepsy surgery have a good chance to become sensitive to anticonvulsant medication, suggesting that the resected brain tissue is responsible for drug resistance. Here, we address the question whether P-glycoprotein (Pgp and multidrug resistance associated proteins (MRPs expressed in the resected tissue contribute to drug resistance in vitro. Effects of anti-epileptic drugs (carbamazepine, sodium valproate, phenytoin and two unspecific inhibitors of Pgp and MRPs (verapamil and probenecid on seizure-like events induced in slices from 35 hippocampal and 35 temporal cortex specimens of altogether 51 patients (161 slices were studied. Although in slice preparations the blood brain barrier is not functional, we found that seizure-like events predominantly persisted in the presence of anticonvulsant drugs (90% and also in the presence of verapamil and probenecid (86%. Following subsequent co-administration of antiepileptic drugs and drug transport inhibitors, seizure-like events continued in 63% of 143 slices. Drug sensitivity in slices was recognized either as transition to recurrent epileptiform transients (30% or as suppression (7%, particularly by perfusion with carbamazepine in probenecid containing solutions (43%, 9%. Summarizing responses to co-administration from more than one slice per patient revealed that suppression of seizure-like activity in all slices was only observed in 7 % of patients. Patients whose tissue was completely or partially sensitive (65 % presented with higher seizure frequencies than those with resistant tissue (35 %. However, corresponding subgroups of patients don’t differ with respect to expression rates of drug transporters. Our results imply that parenchymal MRPs and Pgp are not responsible for drug resistance in resected tissue.

  19. Anti-depressants make amphipods see the light.

    Science.gov (United States)

    Guler, Yasmin; Ford, Alex T

    2010-09-01

    The effects of serotonin altering parasites, serotonin, the anti-depressant fluoxetine, plus two other highly prescribed pharmaceuticals (carbamazepine and diclofenac) on the behaviour of the marine amphipod, Echinogammarus marinus were investigated. Acanthocephalan parasites are known to alter the swimming behaviour in their amphipod hosts through changes in serotonergic activity resulting in increased predation. Behavioural assays were adapted to record changes in phototaxis and geotaxis behaviour in male E. marinus following 7, 14 and 21 days exposure to serotonin and each pharmaceutical compound at 4 concentrations compared to a control (between 10 ng/L and 10 microg/L). E. marinus infected with acanthocephalans parasites had both significantly higher phototaxis and geotaxis scores than those of uninfected specimens. Phototaxis and geotaxis behaviour increased significantly in a concentration-dependent manner with exposure to serotonin. Fluoxetine significantly altered phototaxis and geotaxis activity in what appeared to be a non-monotonic concentration response curve with the greatest behavioural changes observed at 100 ng/L. The main patterns of these behavioural responses were consistent between two trials and the 3 weeks exposure with specimens spending more time within the light and occurring higher in the water column. No obvious trends could be concluded in the phototaxis and geotaxis scores from individuals exposed to carbamazepine or diclofenac as might be expected from their known mode of action. From this study phototaxis and geotaxis behaviour have been observed to be affected by exposure to serotonin modulators. Parasite studies have shown strong links between changes in behaviour and increased predation risk correlating with changes in serotonergic activity. This study has highlighted the potential for highly prescribed anti-depressant drugs to change the behaviour of an ecologically relevant marine species in ways which could conceivably lead to

  20. An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia

    Directory of Open Access Journals (Sweden)

    Siew-Eng Choon

    2012-01-01

    Full Text Available Background: The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR vary among the different populations previously studied. Aim: To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN and drug rash with eosinophilia and systemic symptoms (DRESS in our population. Methods: We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. Results: A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases followed by SJS/TEN (110 cases and DRESS (34 cases. Antibiotics was the most commonly implicated drug group (146 cases followed by anticonvulsants (81 cases and antigout drugs (50 cases. The most frequently implicated drug was allopurinol (50 cases. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases. Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively Conclusions: The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.

  1. Application of passive sampling devices based on multi-walled carbon nanotubes for the isolation of selected pharmaceuticals and phenolic compounds in water samples - possibilities and limitations.

    Science.gov (United States)

    Jakubus, Aleksandra; Tyma, Magdalena; Stepnowski, Piotr; Paszkiewicz, Monika

    2017-03-01

    Nowadays, carbon nanotubes, as commercially available materials, have attracted great attention because of their unique physicochemical properties, especially their strong adsorption abilities. This paper deals with the possibilities and limitations of the application of multi-walled carbon nanotubes as an alternative sorbent in passive sampling devices for the isolation of selected pharmaceuticals and phenolic compounds directly in water samples. Compounds with different properties, including sulfapyridine, sulfamethoxazole, carbamazepine, p-nitrophenol, 17-β-estradiol, 3,5-dichlorophenol and diclofenac were selected as model compounds. Firstly, the influence of several parameters on the extraction efficiency was defined, then the matrix effect and standard validation parameters were established. Under optimized conditions, the proposed analytical methods exhibited good validation parameters, including excellent linearity with R(2) >0.999, the LODs were found to be between 0.01-0.5μgL(-1) and the LOQ ranged from 0.05 to 1.5μgL(-1). Recovery values obtained for model compounds were 79,8±0.2% for sulfapyridine, 41,5±0.1% for sulfamethoxazole, 96,6±1,5% for carbamazepine, 70,5±0.1% for p-nitrophenol, 77,1±0.5% for 17-β-estradiol, 103,1±1.8% for 3,5-dichlorophenol and 76,3±1.4% for diclofenac. This study provides useful data regarding the sorption process on MWCNTs and definitely evaluates the application potential of these types of sorbents in passive sampling devices.

  2. Groundwater quality impacts from the land application of treated municipal wastewater in a large karstic spring basin: chemical and microbiological indicators.

    Science.gov (United States)

    Katz, Brian G; Griffin, Dale W; Davis, J Hal

    2009-04-01

    Geochemical and microbiological techniques were used to assess water-quality impacts from the land application of treated municipal wastewater in the karstic Wakulla Springs basin in northern Florida. Nitrate-N concentrations have increased from about 0.2 to as high as 1.1 mg/L (milligrams per liter) during the past 30 years in Wakulla Springs, a regional discharge point for groundwater (mean flow about 11.3 m(3)/s) from the Upper Floridan aquifer (UFA). A major source of nitrate to the UFA is the approximately 64 million L/d (liters per day) of treated municipal wastewater applied at a 774 ha (hectare) sprayfield farming operation. About 260 chemical and microbiological indicators were analyzed in water samples from the sprayfield effluent reservoir, wells upgradient from the sprayfield, and from 21 downgradient wells and springs to assess the movement of contaminants into the UFA. Concentrations of nitrate-N, boron, chloride, were elevated in water samples from the sprayfield effluent reservoir and in monitoring wells at the sprayfield boundary. Mixing of sprayfield effluent water was indicated by a systematic decrease in concentrations of these constituents with distance downgradient from the sprayfield, with about a 10-fold dilution at Wakulla Springs, about 15 km (kilometers) downgradient from the sprayfield. Groundwater with elevated chloride and boron concentrations in wells downgradient from the sprayfield and in Wakulla Springs had similar nitrate isotopic signatures, whereas the nitrate isotopic composition of water from other sites was consistent with inorganic fertilizers or denitrification. The sprayfield operation was highly effective in removing most studied organic wastewater and pharmaceutical compounds and microbial indicators. Carbamazepine (an anti-convulsant drug) was the only pharmaceutical compound detected in groundwater from two sprayfield monitoring wells (1-2 ppt). One other detection of carbamazepine was found in a distant well water

  3. The degradation behaviour of nine diverse contaminants in urban surface water and wastewater prior to water treatment.

    Science.gov (United States)

    Cormier, Guillaume; Barbeau, Benoit; Arp, Hans Peter H; Sauvé, Sébastien

    2015-12-01

    An increasing diversity of emerging contaminants are entering urban surface water and wastewater, posing unknown risks for the environment. One of the main contemporary challenges in ensuring water quality is to design efficient strategies for minimizing such risks. As a first step in such strategies, it is important to establish the fate and degradation behavior of contaminants prior to any engineered secondary water treatment. Such information is relevant for assessing treatment solutions by simple storage, or to assess the impacts of contaminant spreading in the absence of water treatment, such as during times of flooding or in areas of poor infrastructure. Therefore in this study we examined the degradation behavior of a broad array of water contaminants in actual urban surface water and wastewater, in the presence and absence of naturally occurring bacteria and at two temperatures. The chemicals included caffeine, sulfamethoxazole, carbamazepine, atrazine, 17β-estradiol, ethinylestradiol, diclofenac, desethylatrazine and norethindrone. Little information on the degradation behavior of these pollutants in actual influent wastewater exist, nor in general in water for desethylatrazine (a transformation product of atrazine) and the synthetic hormone norethindrone. Investigations were done in aerobic conditions, in the absence of sunlight. The results suggest that all chemicals except estradiol are stable in urban surface water, and in waste water neither abiotic nor biological degradation in the absence of sunlight contribute significantly to the disappearance of desethylatrazine, atrazine, carbamazepine and diclofenac. Biological degradation in wastewater was effective at transforming norethindrone, 17β-estradiol, ethinylestradiol, caffeine and sulfamethoxazole, with measured degradation rate constants k and half-lives ranging respectively from 0.0082-0.52 d(-1) and 1.3-85 days. The obtained degradation data generally followed a pseudo-first-order-kinetic model

  4. Pan-European survey on the occurrence of selected polar organic persistent pollutants in ground water.

    Science.gov (United States)

    Loos, Robert; Locoro, Giovanni; Comero, Sara; Contini, Serafino; Schwesig, David; Werres, Friedrich; Balsaa, Peter; Gans, Oliver; Weiss, Stefan; Blaha, Ludek; Bolchi, Monica; Gawlik, Bernd Manfred

    2010-07-01

    This study provides the first pan-European reconnaissance of the occurrence of polar organic persistent pollutants in European ground water. In total, 164 individual ground-water samples from 23 European Countries were collected and analysed (among others) for 59 selected organic compounds, comprising pharmaceuticals, antibiotics, pesticides (and their transformation products), perfluorinated acids (PFAs), benzotriazoles, hormones, alkylphenolics (endocrine disrupters), Caffeine, Diethyltoluamide (DEET), and Triclosan. The most relevant compounds in terms of frequency of detection and maximum concentrations detected were DEET (84%; 454 ng/L), Caffeine (83%; 189 ng/L), PFOA (66%; 39 ng/L), Atrazine (56%; 253 ng/L), Desethylatrazine (55%; 487 ng/L), 1H-Benzotriazole (53%; 1032 ng/L), Methylbenzotriazole (52%; 516 ng/L), Desethylterbutylazine (49%; 266 ng/L), PFOS (48%, 135 ng/L), Simazine (43%; 127 ng/L), Carbamazepine (42%; 390 ng/L), nonylphenoxy acetic acid (NPE(1)C) (42%; 11 microg/L), Bisphenol A (40%; 2.3 microg/L), PFHxS (35%; 19 ng/L), Terbutylazine (34%; 716 ng/L), Bentazone (32%; 11 microg/L), Propazine (32%; 25 ng/L), PFHpA (30%; 21 ng/L), 2,4-Dinitrophenol (29%; 122 ng/L), Diuron (29%; 279 ng/L), and Sulfamethoxazole (24%; 38 ng/L). The chemicals which were detected most frequently above the European ground water quality standard for pesticides of 0.1 microg/L were Chloridazon-desphenyl (26 samples), NPE(1)C (20), Bisphenol A (12), Benzotriazole (8), N,N'-Dimethylsulfamid (DMS) (8), Desethylatrazine (6), Nonylphenol (6), Chloridazon-methyldesphenyl (6), Methylbenzotriazole (5), Carbamazepine (4), and Bentazone (4). However, only 1.7% of all single analytical measurements (in total 8000) were above this threshold value of 0.1 microg/L; 7.3% were > than 10 ng/L.

  5. Ozone treatment and the depletion of detectable pharmaceuticals and atrazine herbicide in drinking water sourced from the upper Detroit River, Ontario, Canada.

    Science.gov (United States)

    Hua, Wenyi; Bennett, Erin R; Letcher, Robert J

    2006-07-01

    The depletion and degradation of pharmacologically active compounds (PhACs) and pesticides as a function of ozonation in drinking water treatment processes is not well studied. The A.H. Weeks drinking water treatment plant (DWTP) serves the City of Windsor, Ontario Canada, and incorporates ozone treatment into the production of drinking water. This DWTP also operates a real-time, scaled down pilot plant, which has two parallel streams, conventional and ozone plus conventional treatments. In this study water samples were collected from key points in the two streams of the pilot plant system to determine the depletion and influence of seasonal changes in water processing parameters on eighteen major PhACs (and metabolites) and seven s-triazines herbicides. However, only carbamazepine (antiepileptic), caffeine (stimulant), cotinine (metabolite of nicotine) and atrazine were consistently detectable in the raw water intake (low to sub-ng/L level). Regardless of the seasonality, the flocculation-coagulation and dual media filtration steps without ozone treatment resulted in no decrease in analyte concentrations, while decreases of 66-100% (undetectable, method detection limits 0.05-1 ng/L) of the analyte concentrations were observed when ozone treatment was part of the water processing. These findings demonstrate that ozone treatment is highly effective in depleting carbamazepine, caffeine, cotinine, and atrazine, and thus is highly influential in the fate of these compounds in drinking water treatment regardless of the seasonal time frame. Currently very few Canadian DWTPs incorporate ozonation into conventional treatment, which suggests that human exposure to these compounds via drinking water consumption may be an issue in affected communities.

  6. Follow-up findings in regional cerebral blood flow (r-CBF)-SPECT in a case of idiopathic childhood hemidystonia. Functional neuroimaging and pathophysiological implications

    Energy Technology Data Exchange (ETDEWEB)

    Fiedler, A.; Aderbauer, J.; Segerer, H. [St. Hedwig Hospital, Regensburg (Germany). Dept. of Pediatrics; Marienhagen, J.; Bock, E.; Eilles, C. [Univ. Hospital, Regensburg (Germany). Dept. of Nuclear Medicine

    1999-05-01

    A 9 1/2-year-old girl suffered from intermitting tremor and jitteriness of her left hand and oral muscles every 4 to 6 weeks with long lasting episodes. Clinically myoclonias and dystonic positioning of the left arm, hand and facial muscles were seen. No evidence of trauma, infection or inborn errors of metabolism was found. Successful therapy with carbamazepine was initiated while L-DOPA failed. An ictal 99m-Tc-HMPAO-SPECT showed severe asymmetry with focal hyperperfusion of the contralateral right thalamus and basal ganglia as well as of the bifrontal cortex, whereas no anatomical lesions were found by MRI. In contrast, an interictally performed 99m-Tc-HMPAO SPECT showed hypoperfusion or the right thalamus and normalisation of the frontal perfusion under medical treatment. These 99m-Tc-HMPAO-SPECT findings may provide new insights into the localisation and pathophysiological pathways of idiopathic childhood dystonia. (orig.) [Deutsch] Ein 9 1/2jaehriges Maedchen litt an rezidivierenden, langdauernden Schueben von Tremor und Zittern der linken Hand und der perioralen Muskulatur links. Klinisch fanden sich eine dystone Haltung des linken Armes und unerschoepfliche Myoklonien des Armes, der Hand und der Gesichtsmuskulatur links. Trauma, Infektion oder ein Stoffwechseldefekt als Ursache lagen nicht vor. Ein Therapieversuch mit L-DOPA war erfolglos. Unter Gabe von Carbamazepin wurde Beschwerdefreiheit bleibend erreicht. Ein iktuales 99m-Tc-HMPAO-SPECT zeigte eine fokale Hyperperfusion des rechtsseitigen Thalamus und der Basalganglien, sowie des bifrontalen Kortex. Ein interiktuales 99m-Tc-HMPAOSPECT ergab dann eine deutliche Hypoperfusion des rechtseitigen Thalamus bei normalisierter Perfusion des bifrontalen Kortex. Eine kranielle Magnetresonanztomographie (MRI) ergab einen unauffaelligen Befund. Der Vergleich der iktualen und interiktualen Perfusionsverhaeltnisse weist auf neue pathophysiologische Zusammenhaenge bei idiopathischer kindlicher Dystonie hin. (orig.)

  7. Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF.

    Science.gov (United States)

    Alshahrani, Saad M; Lu, Wenli; Park, Jun-Bom; Morott, Joseph T; Alsulays, Bader B; Majumdar, Soumyajit; Langley, Nigel; Kolter, Karl; Gryczke, Andreas; Repka, Michael A

    2015-08-01

    The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7-21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes.

  8. Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

    Science.gov (United States)

    Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

    2015-07-01

    Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively.

  9. Simple SPE-HPLC determination of some common drugs and herbicides of environmental concern by pulsed amperometry.

    Science.gov (United States)

    Rivoira, L; De Carlo, R M; Cavalli, S; Bruzzoniti, M C

    2015-01-01

    In this work the electrochemical behavior of substances of environmental concern [bentazone, atrazine, carbamazepine, phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin, HPPH] on a glassy carbon working electrode (Ag/AgCl reference electrode) was studied with the aim to develop a HPLC method coupled with amperometric detection. Constant potential (DC), pulsed amperometric detection modes were studied. For the pulsed mode, several waveforms were set and investigated. Detection conditions were optimized as a function of eluent pH. In order to reduce the limits of detection and to analyze natural water samples, a SPE protocol was optimized to be coupled to the developed procedure. For this aim, five sorbents of different physico-chemical characteristics were tested optimizing a recovery procedure for each of the cartridge evaluated. At the optimized SPE conditions, recoveries were included in the range (R=90.2-100.5% for all the analytes, with excellent reproducibility (<%, n=3). The method detection limits obtained by pulsed amperometry after the SPE protocol (preconcentration factor 100) were 113 ng L(-1) (0.47 nmol L(-1)), 67 ng L(-1) (0.25 nmol L(-1)), 234 ng L(-1) (1.1 nmol L(-1)), for bentazone, HPPH and carbamazepine, respectively. Robustness of the method was assessed for each analyte at a concentration level corresponding to about three times the limit of detection, through the evaluation of intra-day (n=13) and inter-day tests (4 days, n=52). Finally the method was successfully applied for the analysis of a river sample (Po River, Turin, Italy).

  10. Prioritizing research for trace pollutants and emerging contaminants in the freshwater environment

    Energy Technology Data Exchange (ETDEWEB)

    Murray, Kyle E., E-mail: Kyle.Murray@utsa.ed [Center for Water Research, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0663 (United States); Thomas, Sheeba M. [San Antonio River Authority, San Antonio, TX (United States); Bodour, Adria A. [Air Force Center for Engineering and the Environment (AFCEE), Brooks City-Base, TX (United States)

    2010-12-15

    Organic chemicals have been detected at trace concentrations in the freshwater environment for decades. Though the term trace pollutant indicates low concentrations normally in the nanogram or microgram per liter range, many of these pollutants can exceed an acceptable daily intake (ADI) for humans. Trace pollutants referred to as emerging contaminants (ECs) have recently been detected in the freshwater environment and may have adverse human health effects. Analytical techniques continue to improve; therefore, the number and frequency of detections of ECs are increasing. It is difficult for regulators to restrict use of pollutants that are a human health hazard; scientists to improve treatment techniques for higher priority pollutants; and the public to modify consumption patterns due to the vast number of ECs and the breadth of literature on the occurrence, use, and toxicity. Hence, this paper examines literature containing occurrence and toxicity data for three broad classes of trace pollutants and ECs (industrials, pesticides, and pharmaceuticals and personal care products (PPCPs)), and assesses the relevance of 71 individual compounds. The evaluation indicates that widely used industrials (BPF) and PPCPs (AHTN, HHCB, ibuprofen, and estriol) occur frequently in samples from the freshwater environment but toxicity data were not available; thus, it is important to establish their ADI. Other widely used industrials (BDE-47, BDE-99) and pesticides (benomyl, carbendazim, aldrin, endrin, ethion, malathion, biphenthrin, and cypermethrin) have established ADI values but occurrence in the freshwater environment was not well documented. The highest priority pollutants for regulation and treatment should include industrials (PFOA, PFOS and DEHP), pesticides (diazinon, methoxychlor, and dieldrin), and PPCPs (EE2, carbamazepine, {beta}E2, DEET, triclosan, acetaminophen, and E1) because they occur frequently in the freshwater environment and pose a human health hazard at

  11. Effects of soil properties on the uptake of pharmaceuticals into earthworms.

    Science.gov (United States)

    Carter, Laura J; Ryan, Jim J; Boxall, Alistair B A

    2016-06-01

    Pharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water. These pharmaceuticals may then be taken up by soil organisms possibly resulting in toxic effects and/or exposure of organisms higher up the food chain. This study investigated the influence of soil properties on the uptake and depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences between soil types with BCFs ranging between 30.5 and 115.9. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0 and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in certain treatments the presence of these chemicals in the soil matrices changed the soil pH over time, with a statistically significant pH difference to control samples. The internal pH of E. fetida also changed as a result of incubation in pharmaceutically spiked soil, in comparison to the control earthworms. These results demonstrate that a combination of soil properties and pharmaceutical physico-chemical properties are important in terms of predicting pharmaceutical uptake in terrestrial systems and that pharmaceuticals can modify soil and internal earthworm chemistry which may hold wider implications for risk assessment.

  12. The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

    Science.gov (United States)

    Mohammad, Othman; Osser, David N

    2014-01-01

    This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

  13. PPCP degradation by UV/chlorine treatment and its impact on DBP formation potential in real waters.

    Science.gov (United States)

    Yang, Xin; Sun, Jianliang; Fu, Wenjie; Shang, Chii; Li, Yin; Chen, Yiwei; Gan, Wenhui; Fang, Jingyun

    2016-07-01

    The ultraviolet/chlorine (UV/chlorine) water purification process was evaluated for its ability to degrade the residues of pharmaceuticals and personal care products (PPCPs) commonly found in drinking water sources. The disinfection byproducts (DBPs) formed after post-chlorination were documented. The performance of the UV/chlorine process was compared with that of the UV/hydrogen peroxide (UV/H2O2) process in treating three types of sand-filtered natural water. Except caffeine and carbamazepine residues, the UV/chlorine process was found to be 59-99% effective for feed water with a high level of dissolved organic carbon and alkalinity, and 27-92% effective for water with a high ammonia content. Both chlorine radicals and hydroxyl radicals were found to contribute to the observed PPCP degradation. The removal efficiencies of chlorine- and UV-resistant PPCPs such as carbamazepine and caffeine were 2-3 times greater than in the UV/H2O2 process in waters not enriched with ammonia. UV/chlorine treatment slightly enhanced the formation chloral hydrate (CH), haloketone (HK) and trichloronitromethane (TCNM). It reduced haloacetonitrile (HAN) formation during the post-chlorination in comparison with the UV/H2O2 process. In waters with high concentrations of ammonia, the UV/chlorine process was only 5-7% more effective than the UV/H2O2 process, and it formed slightly more THMs, HKs and TCNM along with reduced formation of CH and HAN. The UV/chlorine process is thus recommended as a good alternative to UV/H2O2 treatment for its superior PPCP removal without significantly enhancing DBP formation.

  14. Assessing the cost-effectiveness of new pharmaceuticals in epilepsy in adults: the results of a probabilistic decision model.

    Science.gov (United States)

    Hawkins, Neil; Epstein, David; Drummond, Michael; Wilby, Jennifer; Kainth, Anita; Chadwick, David; Sculpher, Mark

    2005-01-01

    Epilepsy currently affects more than 400,000 people in the United Kingdom and 2.3 million in the United States. Drug therapy is the mainstay of treatment for patients with epilepsy, but therapies vary widely in their mechanism of action and acquisition cost. This article describes a decision model developed for the National Institute for Clinical Excellence in the United Kingdom. It compares the long-term cost-effectiveness of drugs licensed in adults for use in 3 situations: monotherapy for newly diagnosed patients, monotherapy for refractory patients, and combination therapy for refractory patients. The analysis separately considers the treatment of partial and generalized seizures. The full range of pharmaceutical therapies feasibly used in the UK health system was included in the analysis. The analysis showed that, on the basis of existing evidence, for newly diagnosed patients with partial seizures, carbamazepine and valproate are likely to be the most cost-effective mono-therapies. Carbamazepine is likely to be the most cost-effective 2nd-line monotherapy for refractory patients, and oxcarbazepine would probably be the most cost-effective adjunctive therapy for refractory patients if the willingness to pay for additional health benefits is greater than 18,000 pounds per quality-adjusted life year (QALY). For patients with generalized seizures, valproate is most likely to be cost-effective for newly diagnosed patients. For refractory patients, adjunctive topiramate is more cost-effective than monotherapy alone if the willingness to pay for additional health benefits is greater than 35,000 pounds per QALY. There is, however, considerable uncertainty regarding these results. Some of the methodological features of the study will be of value in designing cost-effectiveness analyses of other therapies for chronic conditions. These include the methods used to deal with the absence of head-to-head trial data and the need to reflect time dependency in Markov

  15. Uptake of Three Antibiotics and an Antiepileptic Drug by Wheat Crops Spray Irrigated with Wastewater Treatment Plant Effluent.

    Science.gov (United States)

    Franklin, Alison M; Williams, Clinton F; Andrews, Danielle M; Woodward, Emily E; Watson, John E

    2016-03-01

    With rising demands on water supplies necessitating water reuse, wastewater treatment plant (WWTP) effluent is often used to irrigate agricultural lands. Emerging contaminants, like pharmaceuticals and personal care products (PPCPs), are frequently found in effluent due to limited removal during WWTP processes. Concern has arisen about the environmental fate of PPCPs, especially regarding plant uptake. The aim of this study was to analyze uptake of sulfamethoxazole, trimethoprim, ofloxacin, and carbamazepine in wheat ( L.) plants that were spray-irrigated with WWTP effluent. Wheat was collected before and during harvest, and plants were divided into grain and straw. Subsamples were rinsed with methanol to remove compounds adhering to surfaces. All plant tissues underwent liquid-solid extraction, solid-phase extraction cleanup, and liquid chromatography-tandem mass spectrometry analysis. Residues of each compound were present on most plant surfaces. Ofloxacin was found throughout the plant, with higher concentrations in the straw (10.2 ± 7.05 ng g) and lower concentrations in the grain (2.28 ± 0.89 ng g). Trimethoprim was found only on grain or straw surfaces, whereas carbamazepine and sulfamethoxazole were concentrated within the grain (1.88 ± 2.11 and 0.64 ± 0.37 ng g, respectively). These findings demonstrate that PPCPs can be taken up into wheat plants and adhere to plant surfaces when WWTP effluent is spray-irrigated. The presence of PPCPs within and on the surfaces of plants used as food sources raises the question of potential health risks for humans and animals.

  16. Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants.

    Science.gov (United States)

    Marsoni, Milena; De Mattia, Fabrizio; Labra, Massimo; Bruno, Antonia; Bruno, Antonella; Bracale, Marcella; Vannini, Candida

    2014-10-01

    Pharmaceutically active compounds (PACs) are continuously dispersed into the environment due to human and veterinary use, giving rise to their potential accumulation in edible plants. In this study, Eruca sativa L. and Zea mays L. were selected to determine the potential uptake and accumulation of eight different PACs (Salbutamol, Atenolol, Lincomycin, Cyclophosphamide, Carbamazepine, Bezafibrate, Ofloxacin and Ranitidine) designed for human use. To mimic environmental conditions, the plants were grown in pots and irrigated with water spiked with a mixture of PACs at concentrations found in Italian wastewaters and rivers. Moreover, 10× and 100× concentrations of these pharmaceuticals were also tested. The presence of the pharmaceuticals was tested in the edible parts of the plants, namely leaves for E. sativa and grains for Z. mays. Quantification was performed by liquid chromatography mass spectroscopy (LC/MS/MS). In the grains of 100× treated Z. mays, only atenolol, lincomycin and carbamazepine were above the limit of detection (LOD). At the same concentration in E. sativa plants the uptake of all PACs was >LOD. Lincomycin and oflaxacin were above the limit of quantitation in all conditions tested in E. sativa. The results suggest that uptake of some pharmaceuticals from the soil may indeed be a potential transport route to plants and that these environmental pollutants can reach different edible parts of the selected crops. Measurements of the concentrations of these pharmaceuticals in plant materials were used to model potential adult human exposure to these compounds. The results indicate that under the current experimental conditions, crops exposed to the selected pharmaceutical mixture would not have any negative effects on human health. Moreover, no significant differences in the growth of E. sativa or Z. mays plants irrigated with PAC-spiked vs. non-spiked water were observed.

  17. A review of toxic epidermal necrolysis management in Japan

    Directory of Open Access Journals (Sweden)

    Yuri Kinoshita

    2017-01-01

    Full Text Available Toxic epidermal necrolysis (TEN is a severe adverse drug reaction characterized by necrosis of the epidermis. Its incidence is approximately 1 per million a year and average mortality rate is high at 25–50%. TEN has a flu-like prodrome, followed by atypical, targetoid erythematous or purpuric macules on the skin. These macules coalesce to form flaccid blisters that slough off as areas of epidermal necrosis. Drugs such as allopurinol, sulfonamides, and carbamazepine are the most common causes. The human leukocyte antigen (HLA-B*15:02 in Asians being administered carbamazepine and the HLA-B*58:01 antigen in patients of all ethnicities being administered allopurinol are known to be high-risk factors. Rapid diagnosis, discontinuation of the causative drug, and supportive treatment are essential for better prognosis and improvement of sequelae. Till now, systemic corticosteroids and intravenous immunoglobulins have been used as the most common active interventions; however, no gold standard has been established. In Japan, physicians follow a unique diagnostic criteria and treatment guideline to improve the diagnosis rate and streamline treatments. This may be a contributing factor for the lower mortality rate (14.3%. The efficacy of systemic corticosteroids, immunoglobulins, and plasmapheresis may have been beneficial as well. In Japan, TEN is defined as an epidermal detachment of over 10% of the body surface area (BSA, while the globally accepted definition established by Bastuji-Garin describes it as an epidermal detachment of over 30% of the BSA. In Japanese individuals, HLA-A*02:06, HLA-A*02:07, HLA-A*31:01 and HLA-B*51:01 may be linked to higher risks of TEN.

  18. Tracking artificial sweeteners and pharmaceuticals introduced into urban groundwater by leaking sewer networks.

    Science.gov (United States)

    Wolf, Leif; Zwiener, Christian; Zemann, Moritz

    2012-07-15

    There is little quantitative information on the temporal trends of pharmaceuticals and other emerging compounds, including artificial sweeteners, in urban groundwater and their suitability as tracers to inform urban water management. In this study, pharmaceuticals and artificial sweeteners were monitored over 6 years in a shallow urban groundwater body along with a range of conventional sewage tracers in a network of observation wells that were specifically constructed to assess sewer leakage. Out of the 71 substances screened, 24 were detected at above the analytical detection limit. The most frequent compounds were the iodinated X-ray contrast medium amidotrizoic acid (35.3%), the anticonvulsant carbamazepine (33.3%) and the artificial sweetener acesulfame (27.5%), while all other substances occurred in less than 10% of the screened wells. The results from the group of specifically constructed focus wells within 10 m of defective sewers confirmed sewer leaks as being a major entrance pathway into the groundwater. The spatial distribution of pharmaceuticals and artificial sweeteners corresponds well with predictions by pipeline leakage models, which operate on optical sewer condition monitoring data and hydraulic information. Correlations between the concentrations of carbamazepine, iodinated X-ray contrast media and artificial sweeteners were weak to non-existent. Peak concentrations of up to 4130 ng/l of amidotrizoic acid were found in the groundwater downstream of the local hospital. The analysis of 168 samples for amidotrizoic acid, taken at 5 different occasions, did not show significant temporal trends for the years 2002-2008, despite changed recommendations in the medical usage of amidotrizoic acid. The detailed results show that the current mass balance approaches for urban groundwater bodies must be adapted to reflect the spatially distributed leaks and the variable wastewater composition in addition to the lateral and horizontal groundwater fluxes.

  19. Neurodevelopmental effects of prenatal exposure to psychotropic medications.

    Science.gov (United States)

    Gentile, Salvatore

    2010-07-01

    Until now, studies on the reproductive safety of psychotropics have typically assessed the risk of congenital malformations and perinatal complications associated with in utero exposure to such medications. However, little is known of their inherent potential neurobehavioral teratogenicity. The objective is to analyze available data from studies investigating developmental outcome of children exposed prenatally to psychotropics. A computerized Medline/PubMed/TOXNET/ENBASE search (1960-2010) was conducted using the following keywords: pregnancy, child/infant development/neurodevelopment, antidepressants, benzodiazepines, mood stabilizers, and antipsychotics. A separate search was also run to complete the safety profile of single specific medications. Resultant articles were cross-referenced for other relevant articles not identified in the initial search. A noncomputerized review of pertinent journals and textbooks was also performed. All studies published in English and reporting primary data on the developmental outcome of infants exposed in utero to psychotropics and born without malformations were collected. As regards antiepileptic drugs, only studies that provided data on specific medications approved for psychiatric practice use (carbamazepine, lamotrigine, and valproate) were considered. Data were extracted from 41 articles (38 identified electronically and 3 nonelectronically), which met the inclusion criteria. Despite reviewed studies showing relevant methodological limitations, concordant, albeit preliminary, information seems to exclude that prenatal exposure to both selective serotonin reuptake inhibitors and tricyclic antidepressants may interfere with the infants' psychological and cognitive development. Conversely, information on valproate strongly discourages its use in pregnant women. Moreover, although data on carbamazepine remain controversial, information on whole classes of drugs and single medications is either absent (second

  20. Low potency and limited efficacy of antiepileptic drugs in the mouse 6 Hz corneal kindling model.

    Science.gov (United States)

    Leclercq, K; Matagne, A; Kaminski, R M

    2014-05-01

    Corneal kindling is a useful alternative to electrically induced amygdala or hippocampal kindling, which requires advanced surgical and EEG techniques that may not be easily available in many laboratories. Therefore the first aim of this study was to evaluate whether repeated 6 Hz corneal stimulation in mice would lead to an increased and persistent seizure response as described for higher frequency (50/60 Hz) corneal kindling. Male NMRI mice stimulated twice daily (except weekends) for 3 s with 6 Hz electrical current at 44 mA displayed robust kindling development, i.e., a progressive increase in seizure severity. The majority of the animals (about 90%) developed a fully kindled state, defined as at least 10 consecutive stage 3-5 seizures within 5 weeks of corneal stimulation. Afterwards, the fully kindled state was maintained for at least 8 weeks with only two days of stimulations per week. Next, the protective efficacy of four mechanistically different antiepileptic drugs (AEDs; clonazepam, valproate, carbamazepine and levetiracetam) was assessed and compared between 6 Hz and 50 Hz fully kindled mice. All tested AEDs showed a relatively lower potency in the 6 Hz kindling model and a limited efficacy against partial seizures was observed with carbamazepine and levetiracetam. We can conclude that 6 Hz kindling may be more advantageous than the previously described 50/60 Hz corneal kindling models due to its robustness and persistence of the fully kindled state. Furthermore, the observed low potency and limited efficacy of AEDs in 6 Hz fully kindled mice suggest that this model could be a useful tool in the discovery of novel AEDs targeting treatment resistant epilepsy.