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Sample records for carbamazepine

  1. 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

  2. Extracorporeal treatment for carbamazepine poisoning

    DEFF Research Database (Denmark)

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

    2014-01-01

    -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...... is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D...... mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous renal replacement therapies (3D) are alternatives if hemodialysis is not available. MDAC therapy should be continued during ECTR (1D). CONCLUSION...

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

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    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.

  4. Carbamazepine for acute psychosis with eeg abnormalities

    OpenAIRE

    Ivković Maja; Damjanović Aleksandar; Marinković Dragan; Paunović Vladimir R.

    2004-01-01

    Aim. To investigate the efficacy of carbamazepine as adjuvant drug therapy in acute paranoid psychosis with associated EEG abnormalities, compared to sole antipsychotic treatment. Methods. Eleven medication-naive patients diagnosed with acute paranoid psychosis with associated EEG abnormalities were divided into two treatment groups: sole fluphenazine group, with flexible dosing of 5-10 mg/day (n=6), and carbamazepine group (n=5) with the addition of carbamazepine (600 mg/day) to fluphenazine...

  5. Carbamazepine

    Science.gov (United States)

    Teril® Suspension ... acting) tablet, an extended-release capsule, and a suspension (liquid) to take by mouth. The regular tablet, ... may make you drowsy. Do not drive a car or operate machinery until you know how this ...

  6. Carbamazepine for acute psychosis with eeg abnormalities

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    Ivković Maja

    2004-01-01

    Full Text Available Aim. To investigate the efficacy of carbamazepine as adjuvant drug therapy in acute paranoid psychosis with associated EEG abnormalities, compared to sole antipsychotic treatment. Methods. Eleven medication-naive patients diagnosed with acute paranoid psychosis with associated EEG abnormalities were divided into two treatment groups: sole fluphenazine group, with flexible dosing of 5-10 mg/day (n=6, and carbamazepine group (n=5 with the addition of carbamazepine (600 mg/day to fluphenazine treatment. Clinical Global Impression (CGI, Brief Psychiatric Rating Scale (BPRS, Scale for the Assessment of Negative Symptoms (SANS, and EEG were assessed on the baseline and after 6 weeks of treatment. Paired and two-tailed t-tests were used for statistical significance. Results. All the patients showed significant improvement of mental state after 6 weeks of treatment with no significant differences in CGI, BPRS, and total SANS scores in relation to the therapy with carbamazepine. Nevertheless, after 6 weeks of the treatment, EEG findings were significantly better in carbamazepine group, in relation to the findings from the onset of the treatment, as well as in comparison to sole fluphenazine group. Conclusion. Although carbamazepine stabilized abnormal brain electrical activities it seemed that the associated EEG abnormalities were not significant for acute psychosis observed. These preliminary results suggested that there was no convincing evidence that carbamazepine was efficient as the augmentation of antipsychotic treatment for patients with both acute paranoid psychosis and EEG abnormalities.

  7. Is carbamazepine safe to take during pregnancy?

    OpenAIRE

    Matlow, Jeremy; Koren, Gideon

    2012-01-01

    Question Some of my pregnant patients are afraid to take their antiepileptic drugs during pregnancy because of the known risk of malformations and the neurodevelopmental problems associated with valproic acid. Are there similar concerns with carbamazepine?

  8. 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 ...

  9. 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.

  10. 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.

  11. 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 \

  12. Advanced photochemical oxidation of emergent micropollutants: carbamazepine.

    Science.gov (United States)

    Domínguez, Joaquín R; González, Teresa; Palo, Patricia; Cuerda-Correa, Eduardo M

    2014-01-01

    The combination of UV radiation with hydrogen peroxide has been widely used for the photodegradation of pollutants in aqueous solutions. Statistical design of experiments is a powerful tool to optimize this kind of process. Initial hydrogen peroxide concentration, pH and temperature were considered as the variables for the process optimization. The interactions existing between these three variables were analyzed. Initial concentration of hydrogen peroxide proved to be the most important variable conditioning the removal efficiency, followed by temperature, and pH shows a non-significant positive influence along the whole operation interval. The ANOVA test reported significance for five of the nine involved variables. The Response Surface Methodology technique was used to optimize carbamazepine degradation. Under optimal conditions (hydrogen peroxide concentration = 0.38·10(-3) mol L(-1), pH = 1 and temperature = 35.6°C) total carbamazepine degradation was achieved. PMID:24798897

  13. Ecotoxicity of carbamazepine and its UV photolysis transformation products

    DEFF Research Database (Denmark)

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

    2013-01-01

    Carbamazepine, an anti-epileptic pharmaceutical agent commonly found in wastewater, is highly recalcitrant to standard wastewater treatment practices. This study investigated the mixture toxicity of carbamazepine transformation products formed during ultraviolet (UV) photolysis using three standard...... 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...... 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...

  14. PREPARATION AND CHARACTERIZATION OF SPRAY DRIED MICROPARTICLE OF CARBAMAZEPINE

    OpenAIRE

    Dixit Mudit; Kulkarni Parthasarathi Keshavarao; Johri Akash; Kini G Ashwini

    2011-01-01

    Carbamazepine, an antiepileptic drug, exhibits poor water solubility and flow properties, poor dissolution and poor wetting. Consequently, the aim of this study was to improve the dissolution of Carbamazepine. Microparticle containing Carbamazepine was produced by spray drying using Isopropyl alcohol and water in the ratio of 40:60 (v/v) as solvent system to enhance dissolution rate. The prepared formulations were evaluated for in vitro dissolution and solubility. The prepared drug particles ...

  15. 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.

  16. 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.

  17. Formulation and optimization of carbamazepine floating tablets

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    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.

  18. Oxidative Status in Epileptic Children Using Carbamazepine

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    Murat Tutanc

    2015-12-01

    Full Text Available Background: There is an increasing attention towards the relationship between oxidative stress and epilepsy. The effect of antiepileptic drugs on oxidant status is of major interest. Antiepileptic drugs can increase levels of free radicals, which consequently might lead to seizures. Carbamazepine (CBZ is an antiepileptic drug commonly used in childhood and adolescence. Objectives: Therefore we aimed to investigate the effects of CBZ on total antioxidant status, total oxidant stress, and oxidative stress index. Patients and Methods: The study included 40 epileptic patients and 31 healthy children between 4 and 12 years of age. Serum CBZ level, total antioxidant capacity and total oxidant status were measured. Oxidative stress index was also calculated both in controls and patients. Results: In the epileptic group, decreased levels of total antioxidant capacity, increased total oxidative stress and oxidative stress index levels were found. Positive correlation between plasma CBZ levels and total oxidant status was observed. Conclusions: Antioxidant action could not be playing any role in antiepileptic effect of CBZ. Furthermore, increased oxidative stress induced by CBZ could be the cause of CBZ-induced seizures. Therefore combining CBZ with antioxidants could be beneficial.

  19. Aggravation of symptomatic occipital epilepsy of childhood by carbamazepine

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    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.

  20. 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.

  1. 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.

  2. Inadequacy of carbamazepine-spiked model wastewaters for testing photocatalysis efficiency.

    Science.gov (United States)

    Gulyas, Holger; Ogun, Moses Kolade; Meyer, Wibke; Reich, Margrit; Otterpohl, Ralf

    2016-01-15

    The study was performed in order to clarify whether carbamazepine-spiked solutions used as model wastewaters are suitable for the assessment of carbamazepine removal from real secondary municipal effluents by photocatalytic oxidation in the presence and absence of activated carbon. Therefore, carbamazepine (10 mg L(-1)) was dissolved in deionized water or in secondary municipal effluent. Photocatalytic oxidation of these model wastewaters was carried out with TiO2 "P25" (100 mg L(-1)) and UV-A lamps in the absence and in the presence of 20 mg L(-1) powdered activated carbon (PAC). Carbamazepine was analyzed photometrically. In deionized water at pH 5.5, carbamazepine was nearly completely removed with a UV dose of 6.48 kJ L(-1). A similar efficiency of photocatalytic oxidation of carbamazepine added to secondary effluent was observed when the suspension pH was 2.7, while at pH 8 and 10.6, carbamazepine removal from spiked secondary effluent with the same UV dose was only 40 and 60%, respectively. Although PAC addition resulted in an initial adsorptive carbamazepine reduction of 20 to 35% from the model wastewaters, it did not lead to markedly enhanced carbamazepine removal in the subsequent photocatalysis phase. During photocatalytic oxidation of unspiked secondary effluent (initial carbamazepine concentration: 133 ng L(-1)) at pH 7.3 with and without PAC, carbamazepine concentrations were analyzed by HPLC/MS/MS. While PAC addition resulted in the adsorption of about 90% of the initial carbamazepine, photocatalysis did not lead to any carbamazepine removal at all. This indicates that the experiments with spiked model wastewaters – even in a secondary effluent matrix – are absolutely inadequate for predicting photocatalytic carbamazepine removal under real conditions. PMID:26544890

  3. Efficiency of combined carbamazepine and nootropics to reduce side effect of anticonvulsant therapy

    Directory of Open Access Journals (Sweden)

    Ivanov A.V.

    2013-01-01

    Full Text Available Background. The high rate of epileptic disease spreading determines the need of antiepileptic drugs investigation. Carbamazepine, being one of the most effective anticonvulsant drugs, has a wide spectrum of common side effects, and one of the supposed ways to solve this problem is to combine carbamazepine with nootrops. The possibility of the combined anticonvulsant and nootropic therapy still needs further researches. Objective. To study the efficiency of the combined carbamazepine and nootrops use in the experiment on rats and mice to reduce the side effects of anticonvulsant therapy in the form of impaired cognitive brain function and performance. Methods. The research was conducted on 50 white rats and 30 white mice divided randomly in 5 groups: group 1 received carbamazepine 40mg/kg; group 2 – carbamazepine 40 mg/kg + pyracetam 500 mg/kg; group 3 – carbamazepine 40 mg/kg + citicoline 500 mg/kg; group 4 – carbamazepine 40 mg/kg + memantine 10 mg/kg; group 5 – intact animals (control group. The myorelaxing effects of the therapy, physical working capacity, neurotoxity of the drugs were estimated on the 4th day of nootrops administration and 30 minutes after single carbamazepine administration. Histological examination of the brain specimens was performed; the doses of carbamazepine used in morphological study were 40 mg/kg, 150 mg/kg and 720 mg/kg intragastrally. Results. Administration of carbamazepine occurs moderate morphological changes of brain tissue caused by a reaction on the part of the microvasculature, the severity of which depends on the dose of the drug. Conclusion. The most effective combinations that remove the central side effects of carbamazepine are carbamazepine + gliatilin and carbamazepine + citicoline.

  4. Impact of variability in carbamazepine raw materials on drug release

    OpenAIRE

    Flicker, Felicia

    2011-01-01

    Variability in raw materials presents a challenge for pharmaceutical companies. The varying physicochemical properties can critically influence drug release and bioavailability of the final dosage form. Therefore, a strategy to control this variability is required. In this study the well-established antiepileptic drug carbamazepine (CBZ) was selected as the model drug as it presents one example where variability in raw materials has been linked to bioinequivalence and clinical failures. CBZ s...

  5. PHENYTION, CARBAMAZEPINE, SODIUM VALPROATE AND LAMOTRIGINE INDUCED CUTANEOUS REACTIONS

    OpenAIRE

    M. Ghaffarpour; S. S. Hejazie; M. H. Harirchian; H. Pourmahmoodian

    2005-01-01

    Adverse effects of antiepileptic drugs including cutaneous reactions may not only affect the result of treatment and quality of life, but can also be fatal if severe. Skin rash is more likely to occur during the first few months of treatment. The objective of this study was description of skin rashes in users of four antiepileptic drugs. We identified skin rashes of phenytoin, carbamazepine, sodium valproate and lamotrigine in a prospective descriptive cross sectional study in 1086 cases. Pat...

  6. Factors influencing plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic children and adults.

    Science.gov (United States)

    Lanchote, V L; Bonato, P S; Campos, G M; Rodrigues, I

    1995-02-01

    Plasma carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) concentrations were measured in 160 epileptic patients in order to determine the effect of factors such as age, daily dosing schedule, formulation, and combination with other antiepileptic drugs on these concentrations in relation to the daily dose. The results showed that the CBZ plasma level/dose ratio was affected by all factors studied, whereas the CBZ-E plasma level/dose ratio was affected only by formulation and age. The ratio of CBZ-E to CBZ plasma levels (CBZ-E/CBZ) was affected by daily dosing schedule, age, and combination with other antiepileptic drugs. The present study demonstrated that many factors affect plasma CBZ/dose ratios, explaining the discrepancies observed in the literature. PMID:7725376

  7. Molecular recognition study of Carbamazepine, antiseizure drug, by p-t-butyl calix(8)arene

    Science.gov (United States)

    Meenakshi, C.; Jayabal, P.; Ramakrishnan, V.

    2014-03-01

    The formation of inclusion complex of Carbamazepine, a antiseizure drug molecule, with the supra molecule, p-t-butyl calix(8)arene was studied. p-t-Butyl calix(8)arene was the host molecule and Carbamazepine was the guest molecule. Optical absorption spectral studies were carried out to study the molecular recognition properties of p-t-butyl calix(8)arene with Carbamazepine. The stochiometry of the host-guest complex and the binding constant were determined.

  8. 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.

  9. Erythema multiforme as the result of taking carbamazepine

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    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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Dose-dependency of the ratio between carbamazepine serum level and dosage in patients with epilepsy.

    Science.gov (United States)

    Kumps, A H

    1981-01-01

    Carbamazepine serum levels have been determined by gas-liquid chromatography in 24 children and 26 adults with epilepsy on chronic carbamazepine treatment. A significant correlation has been found between carbamazepine steady-state levels and doses per kilogram body weight in both children (p less than 0.01) and adults (p less than 0.05). This relationship is characterized by a significant decline in the level/dose ratio with the doses for adults (p less than 0.001) and, to a lesser extent, for children (p less than 0.05). These results are consistent with a dose-dependent bioavailability. PMID:7324091

  15. 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

  16. 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.

  17. Adsorption of carbamazepine by carbon nanotubes: Effects of DOM introduction and competition with phenanthrene and bisphenol A

    International Nuclear Information System (INIS)

    Carbon nanotubes, organic contaminants and dissolved organic matter (DOM) are co-introduced into the environment. Thus, the interactions between these components have to be evaluated to better understand their environmental behavior. In this study, single-walled carbon nanotubes (SWCNTs) were used as sorbent, carbamazepine was the primary adsorbate, and bisphenol A and phenanthrene were used as competitors. Strong competition with bisphenol A and no effect of phenanthrene on adsorption of carbamazepine was obtained. The hydrophobic neutral fraction of the DOM exhibited the strongest reductive effect on carbamazepine adsorption, most probably due to interactions in solution. In contrast, the hydrophobic acid fraction decreased carbamazepine adsorption mainly via direct competition. When DOM and bisphenol A were co-introduced, the adsorption of carbamazepine was significantly reduced. This study suggests that the chemical nature of DOM can significantly affect the sorptive behavior of polar organic pollutants with carbon nanotubes when all are introduced to the aquatic system. Highlights: •Bisphenol A is an efficient competitor for carbamazepine. •Phenanthrene does not compete with carbamazepine. •DOM exhibited strong reductive effect on carbamazepine adsorption by SWCNTs. •HoN fraction decreased carbamazepine adsorption due to interactions in solution. •HoA fraction decreased carbamazepine adsorption via direct competition. -- In multi-component system including the main adsorbate and competitor, DOM exhibited significant effect on adsorption of contaminants by carbon nanotubes

  18. Tipepidine enhances the antinociceptive-like action of carbamazepine in the acetic acid writhing test.

    Science.gov (United States)

    Kawaura, Kazuaki; Miki, Risa; Urashima, Yuri; Honda, Sokichi; Shehata, Ahmed M; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2011-01-25

    Several antidepressants have been used to treat severe pain in clinics. Recently, we reported that the centrally acting non-narcotic antitussive (cough suppressant drug), tipepidine produces an antidepressant-like effect in the forced swimming test, although the mechanism of action appears to be quite different from that of known antidepressants. In the present study, we investigated whether a combination of tipepidine and carbamazepine acts synergistically to induce an antinociceptive effect in the acetic acid-induced writhing test in mice. Prior to studying the combination of tipepidine and carbamazepine, the analgesic action of tipepidine alone was also examined in mice. Tipepidine at 5-40mg/kg i.p. significantly reduced the number of writhes induced by acetic acid in mice. Carbamazepine at 20mg/kg i.p. also significantly reduced the writhing reaction. Furthermore, co-administration of carbamazepine (5 and 10mg/kg, i.p.) and tipepidine (2.5mg/kg i.p.) significantly decreased the number of writhes induced by acetic acid. This finding suggests that a combination of carbamazepine and tipepidine may be a new strategy for the treatment of neuropathic pain such as what occurs in trigeminal neuralgia, because the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic efficacy by microsomal enzyme induction. PMID:21114989

  19. Pharmacokinetic interaction studies of fenugreek with CYP3A substrates cyclosporine and carbamazepine.

    Science.gov (United States)

    Al-Jenoobi, Fahad I; Alam, Mohd Aftab; Alkharfy, Khalid M; Al-Suwayeh, Saleh A; Korashy, Hesham M; Al-Mohizea, Abdullah M; Iqbal, Muzaffar; Ahad, Abdul; Raish, Mohammad

    2014-06-01

    The present study investigated the effect of fenugreek seed powder on disposition of CYP3A substrates, cyclosporine and carbamazepine. Rabbits were treated with fenugreek seed powder (300 mg/kg p.o.) for 8 days and on 8th day the single dose of cyclosporine (30 mg/kg, p.o.) and carbamazepine (40 mg/kg, p.o.) were administered to the corresponding group after 1 h of fenugreek administration. Blood samples were drawn at several time points and analyzed by using UPLC-MS (cyclosporine) and HPLC (carbamazepine). Pharmacokinetic parameters were calculated by using PK Solver. The present investigation reveals that there was no statistically significant difference between pre- and post-treated pharmacokinetic parameters such as AUC(o-t), AUC(o-∞), C(max), T(max), T(1/2), K(el), MRT(o-∞) , V(z/F), and Cl/F for cyclosporine and carbamazepine. Two tailed "P" values for all these pharmacokinetic parameters were more than 0.05, indicating insignificant impact of fenugreek treatment on the disposition of cyclosporine and carbamazepine. Further, fenugreek may also not have any significant effect on the functionality of P-glycoprotein as cyclosporine is a substrate to P-glycoprotein. The outcomes of present study suggested that fenugreek may not likely to interfere cyclosporine and carbamazepine pharmacokinetics, when co-administered with these drugs. PMID:24022709

  20. Pulsed corona discharge oxidation of aqueous carbamazepine micropollutant.

    Science.gov (United States)

    Ajo, Petri; Krzymyk, Ewelina; Preis, Sergei; Kornev, Iakov; Kronberg, Leif; Louhi-Kultanen, Marjatta

    2016-08-01

    The anti-epileptic drug carbamazepine (CBZ) receives growing attention due to slow biodegradation and inherent accumulation in the aquatic environment. The application of a gas-phase pulsed corona discharge (PCD) was investigated to remove CBZ from synthetic solutions and spiked wastewater effluent from a municipal wastewater treatment facility. The treated water was showered between high voltage (HV) wires and grounded plate electrodes, to which ultra-short HV pulses were applied. CBZ was readily oxidized and 1-(2-benzaldehyde)-4-hydroquinazoline-2-one (BQM) and 1-(2-benzaldehyde)-4-hydro-quinazoline-2,4-dione (BQD) were identified as the most abundant primary transformation products, which, contrary to CBZ ozonation data available in the literature, were further easily oxidized with PCD: BQM and BQD attributed to only a minor portion of the target compound oxidized. In concentrations commonly found in wastewater treatment plant effluents (around 5 µg L(-1)), up to 97% reduction in CBZ concentration was achieved at mere 0.3 kW h m(-3) energy consumption, and over 99.9% was removed at 1 kW h m(-3). The PCD application proved to be efficient in the removal of both the parent substance and its known transformation products, even with the competing reactions in the complex composition of wastewater. PMID:26758812

  1. 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.

  2. 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.

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Harold Ray Garner

    2010-02-01

    Full Text Available 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 carbamaze­pine 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

  5. Anti-solvent co-crystallization of carbamazepine and saccharin.

    Science.gov (United States)

    Wang, In-Chun; Lee, Min-Jeong; Sim, Sang-Jun; Kim, Woo-Sik; Chun, Nan-Hee; Choi, Guang J

    2013-06-25

    The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield. PMID:23598078

  6. 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.

  7. Environmental concentration of carbamazepine accelerates fish embryonic development and disturbs larvae behavior.

    Science.gov (United States)

    Qiang, Liyuan; Cheng, Jinping; Yi, Jun; Rotchell, Jeanette M; Zhu, Xiaotong; Zhou, Junliang

    2016-09-01

    Environmental pollution caused by pharmaceuticals has been recognized as a major threat to the aquatic ecosystems. Carbamazepine, as the widely prescribed antiepileptic drug, has been frequently detected in the aquatic environment and has created concerns about its potential impacts in the aquatic organisms. The effects of carbamazepine on zebrafish embryos were studied by examining their phenotype, behavior and molecular responses. The results showed that carbamazepine disturbed the normal growth and development of exposed zebrafish embryos and larvae. Upon exposure to carbamazepine at 1 μg/L, the hatching rate, body length, swim bladder appearance and yolk sac absorption rate were significantly increased. Embryos in treatment groups were more sensitive to touch and light stimulation. At molecular level, exposure to an environmentally relevant concentration (1 μg/L) of carbamazepine disturbed the expression pattern of neural-related genes of zebrafish embryos and larvae. This study suggests that the exposure of fish embryo to antiepileptic drugs, at environmentally relevant concentrations, affects their early development and impairs their behavior. Such impacts may have future repercussions by affecting fish population structure. PMID:27386877

  8. 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.

  9. 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.

  10. 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.

  11. 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)

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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\

  15. 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.

  16. "The effect of solvent and crystallization conditions on habit modification of Carbamazepine "

    Directory of Open Access Journals (Sweden)

    "Bolourtchian N

    2001-07-01

    Full Text Available Physical characteristics of carbamazepine crystals grown from pure ethanol or acetone under different conditions were studied for the morphology of crystals by scanning electron microscope, x-ray powder diffraction and FT-IR, and for thermodynamic properties by differential scanning calorimeter. Also the dissolution behavior and compaction properties of crystals were studied. The results showed that crystallization of carbamazepine using watering-out method produced needle shape crystals while by the other methods such as reducing temperature or solvent evaporation produced polyhedral crystals in alcohol and thin plate-like crystals in acetone. The crystals which were grown from acetone were larger than those from alcohol. Differential scanning calorimetery and x-ray powder diffraction showed no evidence of poly-morphism for carbamazepine crystallized by reducing the temperature or by the solvent evaporation in contrast with the crystals produced by the watering out technique. Crystallization of carbamazepine by different methods especially watering-out technique improved its dissolution rate and compactibility and produced high crushing strength compacts without capping.

  17. 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...

  18. A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group.

    OpenAIRE

    Richens, A; Davidson, D L; Cartlidge, N. E.; Easter, D J

    1994-01-01

    The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up ...

  19. 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.

  20. Optimization of preparation conditions of poly(ε-caprolactone microspheres for controlled release of carbamazepine

    Directory of Open Access Journals (Sweden)

    Pepić Dragana S.

    2010-01-01

    Full Text Available Poly (ε-caprolactone, PCL, is an aliphatic polyester suitable for controlled drug release due to its biodegradability, biocompatibility, non-toxicity and high permeability to many therapeutic drugs. This study investigates the effect of the preparation parameters on the size and the morphology of the PCL microspheres and on the release profile of carbamazepine from these microspheres. The PCL microspheres were prepared using oil-in-water (o/w emulsion solvent evaporation method with the poly(vinyl alcohol, PVA, as the emulsion stabilizer. The influence of the stirring rate applied during the emulsion formation, the homogenization time and the emulsifier concentration on diameter and size distribution of the microspheres was analyzed by scanning electron microscope (SEM. The initial emulsion was formed applying high stirring rates of 10000, 18000 and 23000 rpm, for homogenization times: 5, 10 and 15 min. The diameter was strongly influenced by the stirring rate, and the average particle size decreased from 9.2 to 2.8 µm with the increase of the stirring rate. Increasing the amount of PVA in the water phase from 0.2 to 1 mass% improved stabilization of the oil droplets and led to a slight decrease of the average particle diameter. Drug-loaded microspheres were prepared by the same technique using different amounts of carbamazepine (10 and 15 mass%, under given conditions (1 mass% PVA, stirring rate of 18000 rpm for a period of 5 min of emulsion formation. Additionally, microspheres were prepared by applying low stirring rate of 1000 rpm with 10 and 15 mass% of the drug. The SEM analysis showed that microspheres created with 18000 rpm stirring rate, had average diameters of 3-4 µm, and the microspheres prepared with 1000 rpm stirring rate were larger than 100 µm. It was also observed that, in the case of the large microspheres, carbamazepine was deposited on their surfaces, while the small microspheres had smooth surfaces without observable

  1. 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.

  2. Characterization and biodegradation kinetics of a new cold-adapted carbamazepine-degrading bacterium, Pseudomonas sp. CBZ-4.

    Science.gov (United States)

    Li, Ang; Cai, Rui; Di, Cui; Qiu, Tian; Pang, Changlong; Yang, Jixian; Ma, Fang; Ren, Nanqi

    2013-11-01

    Carbamazepine is frequently detected in waters and hardly eliminated during conventional wastewater treatment processes due to its complicated chemical structure and resistance to biodegradation. A carbamazepine-degrading bacterium named CBZ-4 was isolated at a low temperature (10 degreeC) from activated sludge in a municipal wastewater treatment plant. Strain CBZ-4, which can use carbamazepine as its sole source of carbon and energy, was identified as Pseudomonas sp. by the 16S rRNA gene sequence. The composition and percentage of fatty acids, which can reveal the cold-adaptation mechanism of strain CBZ-4, were determined. Strain CBZ-4 can effectively degrade carbamazepine at optimal conditions: pH 7.0, 10 degreeC, 150 r/min rotation speed, and 13% inoculation volume. The average removal rate of carbamazepine was 46.6% after 144 hr of incubation. The biodegradation kinetics of carbamazepine by CBZ-4 was fitted via the Monod model. Vmax and Ks were found to be 0.0094 hr-1 and 32.5 mg/L, respectively. PMID:24552057

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

    OpenAIRE

    Marco Farias; Renato Carneiro

    2014-01-01

    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, multiva...

  4. Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting

    OpenAIRE

    Serralheiro, Ana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

    2014-01-01

    The currently available antiepileptic drugs are typically administered via oral or intravenous (IV) routes which commonly exhibit high systemic distribution into non-targeted tissues, leading to peripheral adverse effects and limited brain uptake. In order to improve the efficacy and tolerability of the antiepileptic drug therapy, alternative administration strategies have been investigated. The purpose of the present study was to assess the pharmacokinetics of carbamazepine administered via ...

  5. Interaction of Carbamazepine with Herbs, Dietary Supplements, and Food: A Systematic Review

    OpenAIRE

    Sophia Yui Kau Fong; Qiong Gao; Zhong Zuo

    2013-01-01

    Background. Carbamazepine (CBZ) is a first-line antiepileptic drug which may be prone to drug interactions. Systematic review of herb- and food-drug interactions on CBZ is warranted to provide guidance for medical professionals when prescribing CBZ. Method. A systematic review was conducted on six English databases and four Chinese databases. Results. 196 out of 3179 articles fulfilled inclusion criteria, of which 74 articles were reviewed and 33 herbal products/dietary supplement/food intera...

  6. Preparation and evaluation of polymeric carbamazepin spherical crystals by emulsion solvent diffusion technique

    OpenAIRE

    Yadav Adhikrao; Yadav Venkat

    2009-01-01

    In this study, a significant effect of different polymers on improving the solubility, dissolution rate, and physicochemical properties of carbamazepine (CBZ) has been demonstareted by emulsion solvent diffusion technique, with ethanol-chloroform-water as the solvent system. The hydrophilic polymers like polyethylene glycol, chitosan, and hydrophobic polymer Eudragit RSPO were used in the recrystallization process. The pure drug CBZ and the prepared spherical crystals of CBZ with different po...

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

    OpenAIRE

    Ivanov A.V.; Opryshko V.I.

    2013-01-01

    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 we...

  8. Solar photo-Fenton like using persulphate for carbamazepine removal from domestic wastewater

    OpenAIRE

    Ahmed, M M; Chiron, Serge

    2014-01-01

    This work aimed at decontaminating biologically treated domestic wastewater effluent from pharmaceutical residues by using sulphate radical based homogeneous photo-Fenton involving persulphate (PS) as an oxidant, ferrous iron (Fe(II)) as a catalyst and simulated solar irradiation as a light source. This is the first time that the beneficiary use of solar energy in PS/Fe(II)/UV-Vis system was evaluated by using carbamazepine (CBZ) as a probe compound. In wastewater, CBZ was fully degraded in 3...

  9. 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...

  10. Pharmaceutical evaluation of carbamazepine modifications: comparative study for photostability of carbamazepine polymorphs by using Fourier-transformed reflection-absorption infrared spectroscopy and colorimetric measurement.

    Science.gov (United States)

    Matsuda, Y; Akazawa, R; Teraoka, R; Otsuka, M

    1994-03-01

    The tablet surface was evaluated without physical damage by means of Fourier-transform infrared reflection-absorption spectroscopy (FT-IR-RAS) and colorimetric measurement (colour difference, delta E) of the carbamazepine polymorphs I, II and III, after photodegradation at two irradiation intensities (3.0 and 12.0 J cm-2s-1) under a near-UV fluorescent lamp. The surface of sample pellets of all crystalline forms turned gradually from white to yellow-orange upon exposure to light, and the discoloration rate of form II was faster than that of forms I and III, indicating that form II was the most unstable of the three. The major photoproducts were identified by HPLC, NMR and MS analyses. The carbamazepine content on the surface of the tablet was determined based on the absorption at 1685 cm-1 attributable to C=O stretch vibration in the FT-IR-RAS spectra before and after irradiation by a near-UV fluorescent lamp. The semilogarithmic plots of the photodegradation profiles of the various polymorphs were straight lines, including the induction period, indicating that degradation of the drug on the surface followed first-order kinetics. The induction periods of all forms were not significantly different. However, the degradation rate constant of form II at 12.0 J cm-2s-1 was 5.1 and 1.5 times larger than those of forms I and III, respectively. PMID:8027920

  11. Simultaneous quantification of three polymorphic forms of carbamazepine in the presence of excipients using Raman spectroscopy.

    Science.gov (United States)

    Farias, Marco; Carneiro, Renato

    2014-01-01

    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. PMID:25207717

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Performance comparison of a co-crystal of carbamazepine with marketed product.

    Science.gov (United States)

    Hickey, Magali B; Peterson, Matthew L; Scoppettuolo, Lisa A; Morrisette, Sherry L; Vetter, Anna; Guzmán, Hector; Remenar, Julius F; Zhang, Zhong; Tawa, Mark D; Haley, Sean; Zaworotko, Michael J; Almarsson, Orn

    2007-08-01

    The carbamazepine: saccharin co-crystal (1) was studied in terms of a series of attributes, including suitability for multi-gram scale-up, propensity for crystal polymorphism, physical stability, in vitro dissolution and oral bioavailability, with the goal of comparing 1 with the marketed form of carbamazepine (Tegretol). Preparation of 1 was achieved on a 30g scale with a conventional cooling crystallization process from alcohol solution without seeding. The compound is not overtly polymorphic. This finding is in contrast to the form diversity of pure carbamazepine, which has four known polymorphs and a host of solvates, including a dihydrate, which is the stable form in the presence of water. Physical and chemical stability of the co-crystal is also shown to be quantitatively similar to the pure drug in the marketed product (Tegretol). Finally, comparison of oral bioavailability of 1 with Tegretol tablets in dogs shows the co-crystal to be a viable alternative to the anhydrous polymorph in formulated solid oral products. The balance of properties and performance of 1 as a model co-crystal is discussed. PMID:17292592

  14. 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.

  15. Application of Fenton-like oxidation as pre-treatment for carbamazepine biodegradation

    OpenAIRE

    Monsalvo, VM.; Pedro, ZM. de; M. Muñoz; Casas, JA; Mohedano, AF.; Rodríguez, JJ

    2015-01-01

    Degradation of carbamazepine (CBZ) upon Fenton-like oxidation has been investigated analyzing the effect of H2O2 dose and temperature at a very low catalyst concentration (2mgL-1 of Fe3+). Fenton-like oxidation allowed complete conversion of CBZ, the oxidation rate depending on the amount of H2O2 used. The addition of the theoretical stoichiometric amount of H2O2 led to the complete conversion of CBZ in 1h reaction time. The reduction of the H2O2 initial concentration down to 10% of the stoic...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Photochemical degradation of atenolol, carbamazepine, meprobamate, phenytoin and primidone in wastewater effluents.

    Science.gov (United States)

    Dong, Mei Mei; Trenholm, Rebecca; Rosario-Ortiz, Fernando L

    2015-01-23

    The photochemical degradation of five pharmaceuticals was examined in two secondary wastewater effluents. The compounds, which included atenolol, carbamazepine, meprobamate, phenytoin and primidone, were evaluated for both direct and sensitized photolysis. In the two wastewaters, direct photolysis did not lead to significant compound degradation; however, sensitized photolysis was an important removal pathway for the five pharmaceuticals. Upon solar irradiation, hydroxyl radical (HO) was quantified using the hydroxylation of benzene and singlet oxygen ((1)O2) formation was monitored following the degradation of furfuryl alcohol. Degradation via sensitized photolysis was observed following five-day exposures for atenolol (69-91%), carbamazepine (67-98%), meprobamate (16-52%), phenytoin (44-85%), and primidone (34-88%). Varying removal is likely a result of the differences in reactivity with transient oxidants. Averaged steady state HO concentrations ranged from 1.2 to 4.0×10(-16)M, whereas the concentrations of (1)O2 were 6.0-7.6×10(-14)M. Partial removal due to presence of HO indicates it was not the major sink for most compounds examined. Other transient oxidants, such as (1)O2 and triplet state effluent organic matter, are likely to play important roles in fates of these compounds. PMID:24798495

  18. 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.

  19. Uptake of carbamazepine by cucumber plants--a case study related to irrigation with reclaimed wastewater.

    Science.gov (United States)

    Shenker, Moshe; Harush, Daniella; Ben-Ari, Julius; Chefetz, Benny

    2011-02-01

    Reclaimed wastewater is an important source of irrigation in semiarid and arid zones. Here we report data on carbamazepine (CBZ) uptake by cucumber plants in hydroponic culture and greenhouse experiments using different soil types irrigated with fresh water or reclaimed wastewater. Data obtained from the hydroponic culture experiments suggest that CBZ is mainly translocated by water mass flow, and thus it is concentrated and accumulated to the largest extent in the mature/older leaves. Carbamazepine concentration in cucumber fruits and leaves was negatively correlated with soil organic matter content. The concentrations of CBZ in the roots and stems were relatively low, and most CBZ in the plant (76-84% of total uptake) was detected in the leaves. A greenhouse experiment using fresh water and reclaimed wastewater spiked, or not, with CBZ at 1 μg L(-1) (typical concentration in effluents) revealed that CBZ can be taken up and bioaccumulated from its background concentration in reclaimed wastewater. Bioaccumulation factor (calculated as the ratio of CBZ concentration in the plant to that in the soil solution) for the fruits (0.8-1) was significantly lower than the value calculated for the leaves (17-20). This study emphasizes the potential uptake of active pharmaceutical compounds by crops in organic-matter-poor soils irrigated with reclaimed wastewater and highlights the potential risks associated with this agricultural practice. PMID:21071061

  20. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    Science.gov (United States)

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils.

  1. 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

  2. A 3-D hydrologic transport model of a water recharge system using carbamazepine and chloride as tracers

    Science.gov (United States)

    Rona, Michael; Gasser, Guy; Negev, Ido; Pankratov, Irena; Elhanany, Sara; Lev, Ovadia; Gvirtzman, Haim

    2014-05-01

    Wastewater recharge facilities are often used as a final water treatment before the discharge to the sea or before water reclamation. These facilities are often located in active aquifers that supply drinking water. Thus, leakage from the water recharge facility and gradual expansion of the underground wastewater plume are of considerable health concern. Hydrological modeling of water recharge systems are widely used as operational and predictive tools. These models rely on distributed water head monitoring and at least one chemical or physical tracer to model solutes' transport. Refractory micropollutants have proven useful in qualitative identification of pollution leakages and for quantification of pollution to a specific site near water recharge facilities. However, their usefulness as tracers for hydrological modeling is still questionable. In this article, we describe a long term, 3-D hydraulic model of a large-scale wastewater effluents recharge system in which a combination of chloride and a refractory micropollutant, carbamazepine is used to trace the solute transport. The combination of the two tracers provides the model with the benefits of the high specificity of the carbamazepine and the extensive historic data base that is available for chloride. The model predicts westward expansion of the pollution plume, whereas a standing front is formed at the east. These trends can be confirmed by the time trace of the carbamazepine concentrations at specific locations. We show that the combination of two tracers accounts better (at least at some locations) for the evolution of the pollution plume than a model based on chloride or carbamazepine alone.

  3. 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. ...

  4. 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. PMID:27351902

  5. Phytoremediation of carbamazepine and its metabolite 10,11-epoxycarbamazepine by C3 and C4 plants.

    Science.gov (United States)

    Ryšlavá, Helena; Pomeislová, Alice; Pšondrová, Šárka; Hýsková, Veronika; Smrček, Stanislav

    2015-12-01

    The anticonvulsant drug carbamazepine is considered as an indicator of sewage water pollution: however, its uptake by plants and effect on metabolism have not been sufficiently documented, let alone its metabolite (10,11-epoxycarbamazepine). In a model system of sterile, hydroponically cultivated Zea mays (as C4 plant) and Helianthus annuus (as C3 plant), the uptake and effect of carbamazepine and 10,11-epoxycarbamazepine were studied in comparison with those of acetaminophen and ibuprofen. Ibuprofen and acetaminophen were effectively extracted from drug-supplemented media by both plants, while the uptake of more hydrophobic carbamazepine was much lower. On the other hand, the carbamazepine metabolite, 10,11-epoxycarbamazepine, was, unlike sunflower, willingly taken up by maize plants (after 96 h 88 % of the initial concentration) and effectively stored in maize tissues. In addition, the effect of the studied pharmaceuticals on the plant metabolism (enzymes of Hatch-Slack cycle, peroxidases) was followed. The activity of bound peroxidases, which could cause xylem vessel lignification and reduction of xenobiotic uptake, was at the level of control plants in maize leaves contrary to sunflower. Therefore, our results indicate that maize has the potential to remove 10,11-epoxycarbamazepine from contaminated soils. PMID:26310701

  6. Carbamazepine as indicator for potential short-term contamination of karst springs

    Science.gov (United States)

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

    2012-04-01

    Karst aquifers are complex systems which vulnerability is very difficult to assess mainly because of the duality of recharge processes and duality of flow. Recharge to a karst aquifer occurs as diffuse or concentrated (sinkholes and dolines). Moreover, karst aquifers are formed by an unsaturated zone comprising soil, epikarst and unsaturated rock matrix, and a saturated zone formed of highly permeable conduits and low permeability matrix storage. In the case of contamination of groundwater by wastewater effluent polluted water can be either transported rapidly and have short term major risk on spring water quality or infiltrate into fractured rock matrix and therefore have a long term effect on the water quality. In order to identify the risk of wastewater infiltrating into an aquifer, researches have focused to date on the identification of indicative wastewater markers. Carbamazepine (CBZ) was frequently detected in surface water as well as in effluents of sewage treatment plants, as less than 10% of carbamazepine are usually eliminated during sewage treatment. Moreover, CBZ is not attenuated in aquifers (Heberer, 2002), is unlikely degradable or adsorbed, and can be detected in groundwater (Clara et al., 2004). Therefore, CBZ is considered to be fairly persistent in groundwater (Tixier et al., 2003), and is consequently regarded as an effective wastewater marker. In this case study, the Jeita spring in Lebanon (spring discharge: 1-20 m3/s) was monitored and sampled for major ions and micro-pollutants following a combined precipitation/snowmelt events. A total of 28 samples (major ions and micro-pollutants) were taken over a total sampling time of 16 days at interval varying between 4 and 24 hours. Based on the variation with time of discharge and electrical conductivity (monitored every 20 minutes) as well as the concentrations of the major ions, a conceptual model showing the response of the aquifer compartments to the precipitation event was generated. A

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

    International Nuclear Information System (INIS)

    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

  8. 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

  9. 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

  10. 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.

  11. Removal of carbamazepine and clofibric acid from water using double templates-molecularly imprinted polymers.

    Science.gov (United States)

    Dai, Chao-meng; Zhang, Juan; Zhang, Ya-lei; Zhou, Xue-fei; Duan, Yan-ping; Liu, Shu-guang

    2013-08-01

    A novel double templates-molecularly imprinted polymer (MIP) was prepared by precipitation polymerization using carbamazepine (CBZ) and clofibric acid (CA) as the double templates molecular and 2-vinylpyridine as functional monomer. The equilibrium data of MIP was well described by the Freundlich isotherm model. Two kinetic models were adopted to describe the experimental data, and the pseudo second-order model well-described adsorption of CBZ and CA on the MIP. Adsorption experimental results showed that the MIP had good selectivity and adsorption capacity for CBZ and CA in the presence of competitive compounds compared with non-imprinted polymer, commercial powdered activated carbon, and C18 adsorbents. The feasibility of removing CBZ and CA from water by the MIP was demonstrated using tap water, lake water, and river water. PMID:23436062

  12. Changes in unbound and total valproic acid concentrations after replacement of carbamazepine with oxcarbazepine.

    Science.gov (United States)

    Battino, D; Croci, D; Granata, T; Bernardi, G; Monza, G

    1992-10-01

    Total and free valproic acid (VPA) concentrations were measured in patients switched from a combined VPA and carbamazepine (CBZ) to a combined VPA and oxcarbazepine (OXC) therapy, both administered in individualized daily doses. Four young epileptic patients (13-17 years old) were studied for a 12-week period, total and free VPA concentrations being analyzed just before and 4 h after the morning dose, at the end of VPA and CBZ therapy, and 2 and 10 weeks after CBZ was replaced by OXC. The expected increase in the level/dose (L/D) ratio of total VPA observed at the end of the study was preceded by a clear-cut increase in the L/D ratio of free VPA, which led to VPA-related side effects and required the retitration of VPA daily doses. PMID:1448844

  13. A within-subject analysis of carbamazepine disposition related to development in children with epilepsy.

    Science.gov (United States)

    Albani, F; Riva, R; Contin, M; Baruzzi, A

    1992-12-01

    The effect of aging on carbamazepine (CBZ) plasma level/dose ratio was evaluated retrospectively in 15 children who were receiving CBZ monotherapy and who were followed up for at least 3 years. Subjects of the study were selected from a population of roughly 4,500 patients attending our therapeutic drug monitoring service during a 12-year period. Results showed that the CBZ plasma level/dose ratio increases within subject during childhood, in agreement with data obtained in between-patient studies. However, the increase is not linear with age, the greatest modifications being observed between 9 and 13 years of age. Weight gain alone does not seem to explain this finding, implicating the involvement of complex physiological changes occurring during puberty. PMID:1485365

  14. 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

  15. Photochemical degradation of atenolol, carbamazepine, meprobamate, phenytoin and primidone in wastewater effluents

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Mei Mei [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States); Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Trenholm, Rebecca [Southern Nevada Water Authority (SNWA), P.O. Box 99954, Las Vegas, NV 89193-9954 (United States); Rosario-Ortiz, Fernando L., E-mail: Fernando.rosario@colorado.edu [Civil, Environmental and Architectural Engineering, 428 UCB, University of Colorado, Boulder, CO 80309 (United States)

    2015-01-23

    Highlights: • The photochemical degradation of 5 compounds was evaluated in wastewater effluents. • Attenuation by sensitized photolysis was the most important degradation pathway. • Hydroxyl radical accounted for most of the degradation for aliphatic compounds. • Other transient oxidants could also significantly impact the degradation of the compounds. - Abstract: The photochemical degradation of five pharmaceuticals was examined in two secondary wastewater effluents. The compounds, which included atenolol, carbamazepine, meprobamate, phenytoin and primidone, were evaluated for both direct and sensitized photolysis. In the two wastewaters, direct photolysis did not lead to significant compound degradation; however, sensitized photolysis was an important removal pathway for the five pharmaceuticals. Upon solar irradiation, hydroxyl radical (HO·) was quantified using the hydroxylation of benzene and singlet oxygen ({sup 1}O{sub 2}) formation was monitored following the degradation of furfuryl alcohol. Degradation via sensitized photolysis was observed following five-day exposures for atenolol (69–91%), carbamazepine (67–98%), meprobamate (16–52%), phenytoin (44–85%), and primidone (34–88%). Varying removal is likely a result of the differences in reactivity with transient oxidants. Averaged steady state HO· concentrations ranged from 1.2 to 4.0 × 10{sup −16} M, whereas the concentrations of {sup 1}O{sub 2} were 6.0–7.6 × 10{sup −14} M. Partial removal due to presence of HO· indicates it was not the major sink for most compounds examined. Other transient oxidants, such as {sup 1}O{sub 2} and triplet state effluent organic matter, are likely to play important roles in fates of these compounds.

  16. 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

  17. 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

  18. Combining boron isotopes and carbamazepine to trace sewage in salinized groundwater: A case study in Cap Bon, Tunisia

    International Nuclear Information System (INIS)

    Highlights: • Boron isotopes and carbamazepine contents were combined to assess groundwater contamination by effluents. • Carbamazepine contents ranged from 20 to 900 ng/L in groundwaters mixed with treated wastewaters. • The chemical and isotopic data showed a high spatial and temporal variability. • The system is highly vulnerable and permanently disturbed by the different temporal dynamics. • Wastewater treatments need to be greatly improved before recharge to prevent further degradation of groundwater quality. - Abstract: The Korba aquifer on the east coast of Cape Bon has been overexploited since the 1960s with a resultant reversal of the hydraulic gradient and a degradation of the quality due to seawater intrusion. In 2008 the authorities introduced integrated water resources planning based on a managed aquifer recharge with treated wastewater. Water quality monitoring was implemented in order to determine the different system components and trace the effectiveness of the artificial recharge. Groundwater samples taken from recharge control piezometers and surrounding farm wells were analyzed for their chemical contents, for their B isotopes, a proven tracer of groundwater salinization and domestic sewage, and their carbamazepine content, an anti-epileptic known to pass through wastewater treatment and so recognized as a pertinent tracer of wastewater contamination. The system equilibrium was permanently disturbed by the different temporal dynamics of continuous processes such as cation exchange, and by threshold processes linked to oxidation–reduction conditions. The B isotopic compositions significantly shifted back-and-forth due to mixing with end-members of various origin. Under the variable contribution of meteoric recharge, the Plio-Quaternary groundwater (δ11B of 35–40.6‰, a mean B concentration of 30 μmol/L, no carbamazepine, n = 7) was subject to seawater intrusion that induced a high δ11B level (δ11B of 41.5–48.0‰, a mean B

  19. A study of the use of carbamazepine, pregabalin and alpha lipoic acid in patients of diabetic neuropathy

    OpenAIRE

    Patel, Niral; Mishra, Vishal; Patel, Prakruti; Ram K Dikshit

    2014-01-01

    Background Diabetic peripheral neuropathy (DPN) is a common, symptomatic, long-term complication of diabetes mellitus. Many of the agents used to treat DN have not been compared with each other. This study was, therefore, undertaken to compare the efficacy and safety of carbamazepine, pregabalin and alpha-lipoic acid in diabetic neuropathy patients. Methods This was a prospective, observational study. The patients were categorized into three groups, Group I included those patients who were pr...

  20. 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....

  1. Electro-oxidation of carbamazepine metabolites: Characterization and influence in the voltammetric determination of the parent drug

    OpenAIRE

    Ginja Teixeira, Jorge; Veiga, Alfredina; Palace Carvalho, Alfredo J.; Martins Teixeira, Dora

    2013-01-01

    Abstract The electro-oxidation behavior of five important metabolites of carbamazepine (CBZ) and their potential influence on the voltammetric determination of the parent drug in biological fluids was investigated for the first time. This investigation was performed using cyclic voltammetry, in combination with controlled potential electrolysis and HPLC-DAD-MS analysis of oxidation products of these compounds. Using a sensitive glassy carbon electrode modified with multi-walled carbon nan...

  2. Region-selective effects of long-term lithium and carbamazepine administration on cyclic AMP levels in rat brain

    International Nuclear Information System (INIS)

    The effect of lithium and carbamazepine in the treatment of bipolar affective disorder is well established. Althougt a number of biochemical effects have been found, the exact molecular mechanisms underlying their therapeutic actions have not been elucidated nor are the target regions in the brain identified. Taken into account the important role of the cyclic AMP second messenger system in the regulation of neuronal exitability and the indications of its involvement in the pathophysiology of bipolar affective disorder, we have focused on the drug effects on cyclic AMP levels. The objectives of this investigation were to measure the effects on basal cyclic AMP levels, and to locate target regions within the rat brain after long-term administration of lithium and carbamazepine. Drug treatments were carried out for a period of 28 days. After either drug treatment the cyclic AMP level was increased 3-4 times in frontal cortex but unchanged in hippocampus, hypothalamus, thalamus, amygdala and in cerebellum. In neostratum the cyclic AMP level was decreased to about 30% after treatment with lithium. We suggest the common region-selective effect, observed for both drugs in frontal cortex, to be essential for the therapeutic actions of lithium and carbamazepine. (au)

  3. (1)H NMR-based metabolomics of Daphnia magna responses after sub-lethal exposure to triclosan, carbamazepine and ibuprofen.

    Science.gov (United States)

    Kovacevic, Vera; Simpson, André J; Simpson, Myrna J

    2016-09-01

    Pharmaceuticals and personal care products are a class of emerging contaminants that are present in wastewater effluents, surface water, and groundwater around the world. There is a need to determine rapid and reliable bioindicators of exposure and the toxic mode of action of these contaminants to aquatic organisms. (1)H nuclear magnetic resonance (NMR)-based metabolomics in combination with multivariate statistical analysis was used to determine the metabolic profile of Daphnia magna after exposure to a range of sub-lethal concentrations of triclosan (6.25-100μg/L), carbamazepine (1.75-14mg/L) and ibuprofen (1.75-14mg/L) for 48h. Sub-lethal triclosan exposure suggested a general oxidative stress condition and the branched-chain amino acids, glutamine, glutamate, and methionine emerged as potential bioindicators. The aromatic amino acids, serine, glycine and alanine are potential bioindicators for sub-lethal carbamazepine exposure that may have altered energy metabolism. The potential bioindicators for sub-lethal ibuprofen exposure are serine, methionine, lysine, arginine and leucine, which showed a concentration-dependent response. The differences in the metabolic changes were related to the dissimilar modes of toxicity of triclosan, carbamazepine and ibuprofen. (1)H NMR-based metabolomics gave an improved understanding of how these emerging contaminants impact the keystone species D. magna. PMID:26809854

  4. 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.

  5. 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. PMID:19150730

  6. Biosorption of clofibric acid and carbamazepine in aqueous solution by agricultural waste rice straw.

    Science.gov (United States)

    Liu, Zhanguang; Zhou, Xuefei; Chen, Xiaohua; Dai, Chaomeng; Zhang, Juan; Zhang, Yalei

    2013-12-01

    Due to their widespread use, clofibric acid (CA) and carbamazepine (CBZ) have been frequently detected simultaneously at relatively high concentrations in aquatic environments. In this study, agricultural waste rice straw was employed as a potentially low-cost, effective and easy-to-operate biosorbent (RSB) to remove CA and CBZ. The adsorption of both pharmaceuticals followed pseudo second-order kinetics, and intraparticle diffusion was an important rate-limiting step. The adsorption isotherms of both drugs were fit well with Freundlich model. The adsorption of CA onto RSB was exothermic and was more likely to be dominated by physical processes, while the adsorption of CBZ was endothermic. Solution pH was determined to be the most important factor for CA adsorption, such that the adsorption capacity of CA onto RSB increased with the decline of solution pH. In the lower range of solution pH below 3.1, the CA removal efficiency was enhanced with the increase of biosorbent dosage. The CBZ removal efficiency was enhanced with the increase of RSB dosage without pH control. The maximum adsorption capacities were 126.3 mg/g for CA and 40.0 mg/g for CBZ. PMID:24649668

  7. 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.

  8. Preparation and evaluation of polymeric carbamazepin spherical crystals by emulsion solvent diffusion technique

    Directory of Open Access Journals (Sweden)

    Yadav Adhikrao

    2009-01-01

    Full Text Available In this study, a significant effect of different polymers on improving the solubility, dissolution rate, and physicochemical properties of carbamazepine (CBZ has been demonstareted by emulsion solvent diffusion technique, with ethanol-chloroform-water as the solvent system. The hydrophilic polymers like polyethylene glycol, chitosan, and hydrophobic polymer Eudragit RSPO were used in the recrystallization process. The pure drug CBZ and the prepared spherical crystals of CBZ with different polymers were characterized in terms of morphology (microscopical photograph, X-ray diffraction (XRD, Fourier transform infrared spectroscopy (FTIR, drug contents, solubility, dissolution rate, crushing strength, wettability, flowability, and packability. The FTIR spectra of the prepared spherical crystals showed that changes in the chemical nature occur and do not present great fingerprint difference. The XRD also revealed a characteristic decrease in crystallinity. The solubility and dissolution studies demonstrated a marked increase in solubility and dissolution rate in comparison with the pure drug. The prepared spherical crystals with different polymers exhibited excellent physicochemical properties like flowability, packability, and wettability compared with the pure drug. The spherical crystals with polyethylene glycol and chitosan showed higher crushing strength when compared with the hydrophobic polymer (Eudragit RSPO.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Jelic, A; Michael, I; Achilleos, A; Hapeshi, E; Lambropoulou, D; Perez, S; Petrovic, M; Fatta-Kassinos, D; Barcelo, D

    2013-12-15

    This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO2-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. PMID:23972790

  11. 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.

  12. Solar photo-Fenton like using persulphate for carbamazepine removal from domestic wastewater.

    Science.gov (United States)

    Ahmed, Moussa Mahdi; Chiron, Serge

    2014-01-01

    This work aimed at decontaminating biologically treated domestic wastewater effluent from pharmaceutical residues by using sulphate radical based homogeneous photo-Fenton involving persulphate (PS) as an oxidant, ferrous iron (Fe(II)) as a catalyst and simulated solar irradiation as a light source. This is the first time that the beneficiary use of solar energy in PS/Fe(II)/UV-Vis system was evaluated by using carbamazepine (CBZ) as a probe compound. In wastewater, CBZ was fully degraded in 30 min for an initial CBZ concentration of 50 μM and an optimal PS:Fe(II) molar ratio of 2:1 thanks to the high selectivity in reactivity of the sulphate radical limiting scavenging effects of organic matter and inorganic ions. Seventeen by-products were identified using liquid chromatography-high resolution-mass spectrometry allowing for the establishment of degradation pathways. CBZ first underwent degradation through one electron transfer oxidation processes due to sulphate radical reactivity followed by hydroxylation processes through hydroxyl radical formed by Fe(III) photoreduction. The sequential generation of sulphate radical and hydroxyl radical has made PS/Fe(II)/UV-Vis a kinetically effective process in removing CBZ from wastewater without the accumulation of toxic intermediates and opens new remediation strategies for tertiary treatment in domestic wastewater treatment plants. PMID:24095595

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

    Science.gov (United States)

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

    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), 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.

  14. 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.

  15. Factors influencing plasma level/dose ratios of carbamazepine and its major metabolites in epileptic children.

    Science.gov (United States)

    Hartley, R; Lucock, M D; Ng, P C; Forsythe, W I; McLain, B; Bowmer, C J

    1990-09-01

    The relationship between daily dose and plasma concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZ-EP), and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZ-DIOL) was investigated in 21 children aged 7-16 years who received CBZ monotherapy, twice daily in equally divided doses. Significant linear correlations between CBZ dose and plasma levels were obtained for CBZ and its metabolites (p less than 0.01). In addition, the effects of daily dose and patients' age on the plasma level/dose ratios for CBZ, CBZ-EP, and CBZ-DIOL were evaluated. A significant negative correlation was observed between the daily dose of CBZ and the CBZ plasma level/dose ratio (p less than 0.01). By contrast, plasma level/dose ratios for CBZ-EP and CBZ-DIOL were independent of dose (p greater than 0.1). On the basis of these observations, we consider that the decrease in CBZ plasma level/dose ratio with increasing CBZ dose appears to be due to dose-dependent metabolic clearance of CBZ. The influence of age on plasma level/dose ratios for CBZ and its metabolites was not significant (p greater than 0.05). However, there was considerable interdose and diurnal variation in the plasma level/dose ratios, particularly for CBZ (28-41%); this must be taken into account when making dose adjustments based on plasma level/dose ratios. PMID:2293405

  16. Application of nanofiltration for the removal of carbamazepine, diclofenac and ibuprofen from drinking water sources.

    Science.gov (United States)

    Vergili, I

    2013-09-30

    Pharmaceutical active compounds (PhACs) are persistent during the process used to treat drinking water and, because drinking water treatment plants are not specifically designed to remove PhACs, these compounds are found in drinking water. Although there are currently no regulations or drinking water directives for PhACs, precautionary principles suggest ensuring maximal removal of PhACs through improved or existing treatment techniques. This study was designed to investigate the performance of a nanofiltration membrane in cross-flow filtration equipment for the removal of three PhACs [carbamazepine (CBZ), diclofenac (DIC) and ibuprofen (IBU)] that were spiked in water taken from a drinking water treatment plant using surface water. Because of their low solubilities, high log Kow values, low dipole moments and negative charges, higher rejection values were obtained for DIC and IBU. Low to moderate rejection values were most likely due to the small molecular sizes of the PhACs (i.e., MW water. Flux declines obtained from DIC studies was attributed to the adsorption of DIC ions inside the membrane pores, which decreases the flux. The most evident change in the FT-IR spectrum after nanofiltration was the appearance of new intense bands at 1072 cm(-1) and 1011 cm(-1), indicating the deposition of calcium salts on the membrane surface.

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

    Science.gov (United States)

    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. Human health risk assessment of pharmaceuticals in water: an uncertainty analysis for meprobamate, carbamazepine, and phenytoin.

    Science.gov (United States)

    Kumar, Arun; Xagoraraki, Irene

    2010-01-01

    This study presents a step-wise development of a quantitative pharmaceutical risk assessment (QPhRA, hereafter) framework, including Monte Carlo uncertainty analysis for meprobamate, carbamazepine, and phenytoin during (1) accidental exposures of stream water and fish consumption and (2) direct ingestion of finished drinking water for children and adults. Average hazard quotients of these pharmaceuticals (i.e., the ratio of values of chronic daily intake to acceptable daily intake) were found to lie between 1x10(-10) and 3x10(-5) and 99 th percentile values of hazard quotients were found to be less than 1x10(-4) for both sub-populations, indicating no potential risks of adverse effects due to pharmaceuticals exposures. In addition, pharmaceutical concentrations were also observed to be lower than their respective calculated acceptable daily intake-equivalent drinking water levels, indicating no potential human health risks. To the authors' knowledge, for the first time in QPhRA studies, this study has attempted to characterize and quantify effects of factors, such as considerations for sensitive sub-populations using subpopulation-specific toxic endpoints and use of pharmaceutical concentrations in stream and finished drinking waters on risk estimates. Acceptable daily intake was observed to be the primary contributor (>93% variance contribution) in the overall uncertainties of estimates of hazard quotients, followed by fish consumptions and pharmaceutical concentrations in water. Further research efforts are required to standardize use of acceptable daily intake values to reduce large variability in estimation of hazard quotients. PMID:20152876

  19. Removal of carbamazepine in aqueous solutions through solar photolysis of free available chlorine.

    Science.gov (United States)

    Yang, Bin; Kookana, Rai S; Williams, Mike; Du, Jun; Doan, Hai; Kumar, Anupama

    2016-09-01

    Removal of a persistent antiepileptic drug carbamazepine (CBZ) in aqueous solutions was investigated by using solar photolysis combined with free available chlorine (FAC). The combination of chlorination with simulated or natural sunlight markedly enhanced removal of CBZ in 10 mM phosphate buffer solution (pH 7.0) and river water (pH 7.0) compared with sunlight or FAC alone. Further analysis indicated that the observed enhancements in CBZ removal can be attributed to the in situ hydroxyl radical (HO) and ozone (O3) production during FAC photolysis. During 70 min simulated sunlight photolysis combined with FAC treatment, HO reaction contributed to 35.8% removal of CBZ and O3 reaction contributed to 40.6% removal, while only 5.3% of CBZ was removed by HOCl reaction. The oxidation products of CBZ, epoxide CBZ, 10,11-dihydro-10,11-dihydroxy CBZ, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) and 4-aldehyde-9-acridone, were mainly formed from the HO and O3 attack at the double bond on the central heterocyclic ring of CBZ. Formation of these oxidation products did not cause any increase or decrease in toxicity to microbial species tested through Microbial Assay for Toxicity Risk Assessment (MARA). The initial FAC concentration and pH had a major influence on the removal process of CBZ during FAC photolysis, while temperature had a minor effect only. The combination of chlorination with natural sunlight could provide an effective approach for removal of CBZ and other contaminants during water treatment. PMID:27232985

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Electrochemical removal of carbamazepine in water with Ti/PbO2 cylindrical mesh anode.

    Science.gov (United States)

    García-Espinoza, J D; Gortáres-Moroyoqui, P; Orta-Ledesma, M T; Drogui, P; Mijaylova-Nacheva, P

    2016-01-01

    Carbamazepine (CBZ) is one of the most frequently detected organic compounds in the aquatic environment. Due to its bio-persistence and toxicity for humans and the environment its removal has become an important issue. The performance of the electrochemical oxidation process and in situ production of reactive oxygen species (ROS), such as O3 and H2O2, for CBZ removal have been studied using Ti/PbO2 cylindrical mesh anode in the presence of Na2SO4 as supporting electrolyte in a batch electrochemical reactor. In this integrated process, direct oxidation at anode and indirect oxidation by in situ electrogenerated ROS can occur simultaneously. The effect of several factors such as electrolysis time, current intensity, initial pH and oxygen flux was investigated by means of an experimental design methodology, using a 2(4) factorial matrix. CBZ removal of 83.93% was obtained and the most influential parameters turned out to be electrolysis time, current intensity and oxygen flux. Later, the optimal experimental values for CBZ degradation were obtained by means of a central composite design. The best operating conditions, analyzed by Design Expert(®) software, are the following: 110 min of electrolysis at 3.0 A, pH = 7.05 and 2.8 L O2/min. Under these optimal conditions, the model prediction (82.44%) fits very well with the experimental response (83.90 ± 0.8%). Furthermore, chemical oxygen demand decrease was quantified. Our results illustrated significant removal efficiency for the CBZ in optimized condition with second order kinetic reaction. PMID:26942539

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

    International Nuclear Information System (INIS)

    Highlights: • Degradation of CBZ during US, TiO2/UV and TiO2/UV/US processes has been evaluated. • The combined TiO2/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, TiO2-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

  4. 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.

  5. 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

  6. Removal of ibuprofen, naproxen and carbamazepine in aqueous solution onto natural clay: equilibrium, kinetics, and thermodynamic study

    Science.gov (United States)

    Khazri, Hassen; Ghorbel-Abid, Ibtissem; Kalfat, Rafik; Trabelsi-Ayadi, Malika

    2016-04-01

    This study aimed to describe the adsorption of three pharmaceuticals compounds (ibuprofen, naproxen and carbamazepine) onto natural clay on the basis of equilibrium parameters such as a function of time, effect of pH, varying of the concentration and the temperature. Adsorption kinetic data were modeled using the Lagergren's first-order and the pseudo-second-order kinetic equations. The kinetic results of adsorption are described better using the pseudo-second order model. The isotherm results were tested in the Langmuir, Freundlich and Dubinin-Radushkevich models. The thermodynamic parameters obtained indicate that the adsorption of pharmaceuticals on the clay is a spontaneous and endothermic process.

  7. Effects of carbamazepine on cortisol levels and behavioral responses to stress in the fish Jenynsia multidentata.

    Science.gov (United States)

    Calcagno, Emilia; Durando, Patricia; Valdés, M Eugenia; Franchioni, Liliana; Bistoni, María de los Ángeles

    2016-05-01

    Carbamazepine (CBZ) is an anticonvulsant drug, prescribed worldwide for the treatment of epilepsy, bipolar disorder and trigeminal neuralgia, which has been frequently detected in aquatic environments. The objective of this study was to analyze if CBZ modifies scototaxis and shoaling behaviors and/or whole-body cortisol levels of the one-sided livebearing fish Jenynsia multidentata under stress condition. Female adults of J. multidentata were exposed to 0, 10, 50 and 200μgCBZ/L during 14days. After CBZ exposure, fish were subjected to restraint stress during 15min. Control animals were not exposed to CBZ or stress. In the light/dark preference test (scototaxis), the individuals under acute restraint stress (without CBZ) exhibited a significant increase in the mean speed and in the time spent both in the light compartment and in the bottom of the tank with respect to controls. They also showed a tendency to stay longer frozen in the light compartment. Fish exposed to 10 and 50μgCBZ/L showed a significant reduction in mean speed compared to stressed fish without CBZ. A reduction in the time spent in the bottom of the tank was also observed in fish exposed to 10μgCBZ/L. Fish exposed to 200μgCBZ/L showed a decreasing tendency in all behavioral endpoints (time spent in the light compartment, mean speed, time spent at the bottom and freezing) in comparison to stressed fish not exposed to CBZ. Considering whole-body cortisol results, fish under acute restraint stress (without CBZ) significantly increased their hormone levels with respect to the control group, while fish exposed to CBZ and acute restraint stress, significantly decreased their whole-body cortisol levels. There were no significant changes in shoaling behavior due to either stress or CBZ exposure and no significant differences in whole-body cortisol levels between experimental groups. Considering that the light/dark and shoaling tests measure different stress response behaviors regulated by different

  8. 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

  9. 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

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

    Science.gov (United States)

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

    2016-06-01

    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. PMID:26900981

  11. Production method of carbamazepine/saccharin cocrystal particles by using two solution mixing based on the ternary phase diagram

    Science.gov (United States)

    Kudo, Shoji; Takiyama, Hiroshi

    2014-04-01

    In the pharmaceutical field, improvement of drug solubility is required, and an interest in cocrystals is growing. Crystallization methods for industrial production of cocrystals have not been developed enough whereas many cocrystals have been prepared in order to find a new crystal form by screening in the laboratory. The objective of this study was the development of the crystallization method which is useful for the industrial production of cocrystal particles based on the phase diagram. A cocrystal of carbamazepine and saccharin was selected as a model substance. The ternary phase diagram of carbamazepine and saccharin in methanol at 303 K was measured. A cocrystallization method of mixing two kinds of different eutectic solutions was designed based on the ternary phase diagram. In order to adjust the cocrystallization conditions, the determination method of the driving force for cocrystal deposition such as supersaturation based on mass balance was proposed. The cocrystal particles were obtained under all the conditions of the five mixing ratios. From these experimental results, the relationship between the supersaturation and the induction time for nucleation was confirmed as well as conventional crystallization. In conclusion, the crystallization method for industrial production of cocrystal particles including the determination of the supersaturation was suggested.

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

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    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.

  13. Carbamazepine-Induced Incomplete Stevens-Johnson Syndrome: Report of a Case in Children without Mycoplasma pneumoniae Infection.

    Science.gov (United States)

    Techasatian, Leelawadee; Panombualert, Sunee; Uppala, Rattapon; Jetsrisuparb, Charoon

    2015-08-01

    Incomplete Stevens-Johnson syndrome (SJS) is a rare reactive skin condition. Most cases are occurred in children and all are associated with Mycoplasma pneumoniae (M. pneumoniae) infection. We reported an unusual case of a 6-year-old boy who developed the presentation of isolated mucosal erosion with a lack of skin findings, which indicated incomplete SJS after two weeks of carbamazepine (CBZ) administration. Findings of positive HLA-B*1502 allele supported a possible causative influence of carbamazepine inducing SJS. Interestingly, this patient was tested negatively for M. pneumoniae. This is a significant finding since there is no previous report of incomplete SJS without M. pneumoniae infection. Discontinuation of CBZ and administration of systemic corticosteroids were accomplished to treat SJS, which resulted in complete recovery. Our interesting findings highlighted the manifestation of incomplete SJS, which can present with other causes rather than M. pneumoniae infection. Early manifestation of mucosal change without typical skin lesions should not be neglected in the diagnosis of incomplete SJS. PMID:26742396

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

    Science.gov (United States)

    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.

  15. How life history influences the responses of the clam Scrobicularia plana to the combined impacts of carbamazepine and pH decrease

    International Nuclear Information System (INIS)

    In the present study, the bivalve Scrobicularia plana, collected from two contrasting areas (pristine location and mercury contaminated area), was selected to assess the biochemical alterations imposed by pH decrease, carbamazepine (an antiepileptic) and the combined effect of both stressors. The effects on oxidative stress related biomarkers after 96 h exposure revealed that pH decrease and carbamazepine induced alterations on clams, with greater impacts on individuals from the contaminated area which presented higher mortality, higher lipid peroxidation and higher glutathione S-transferase activity. These results emphasize the risk of extrapolating results from one area to another, since the same species inhabiting different areas may be affected differently when exposed to the same stressors. Furthermore, the results obtained showed that, when combined, the impact of pH decrease and carbamazepine was lower than each stressor acting alone, which could be related to the defence mechanism of valves closure when bivalves are under higher stressful conditions. - Highlights: • Environmentally relevant concentrations of CBZ and pH 7.1 impacted the performance of Scrobicularia plana. • The combination of CBZ and pH 7.1 did not induce higher impacts compared with stressors acting alone. • Clams from a polluted area showed greater alterations than clams collected from an unpolluted area. - pH decrease and carbamazepine induced biochemical alterations on clams (Scrobicularia plana), with greater impacts on individuals from the contaminated area

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

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    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

  17. 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

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

    International Nuclear Information System (INIS)

    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

  19. 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

  20. 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.

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

    International Nuclear Information System (INIS)

    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 BOD7 m-3d-1. Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (kbiol) 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 gSS−1 d−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. • kbiol 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

  2. 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

  3. The role of sorption and biodegradation in the removal of acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole during soil contact: A kinetics study.

    Science.gov (United States)

    Martínez-Hernández, Virtudes; Meffe, Raffaella; Herrera López, Sonia; de Bustamante, Irene

    2016-07-15

    In countries like Spain, where water is a limited resource, reusing effluents from wastewater treatment plants may imply the introduction of incompletely eliminated pollutants into the environment. Therefore, this work identified the role of sorption and biodegradation in attenuating pharmaceutical compounds (acetaminophen, carbamazepine, caffeine, naproxen and sulfamethoxazole) in natural soil. It also determined which sorption and removal ("sorption+biodegradation") kinetics models describe the behaviour of these substances in the water-soil system. Presence of potential transformation products (TPs) as a result of pharmaceuticals biodegradation was also studied. To this end, serial batch-type experiments were performed with a soil:water ratio of 1:4 and an initial pharmaceutical concentration of 100μgL(-1). Despite results are dependent on soil characteristics, they revealed that, for those substances with a higher affinity to the soil used (loamy sand), sorption seems to play a key role during the first 48h of contact with soil, and gives way to biodegradation afterwards. The sorption of the pharmaceuticals studied follows a pseudo second-order kinetics. Caffeine and sulfamethoxazole displayed the fastest initial sorption velocities (h=2055 and h=228μgkg(-1)h(-1), respectively). The removal kinetics experiments, satisfactorily simulated by the first-order kinetics model, indicated the presence of potential microbial adaptation to degradation. Indeed, half-lives decreased from 1.6- to 11.7-fold with respect to initial values. The microbial capacity to degrade sulfamethoxazole could be a matter of concern if bacteria have developed resistance to this antibiotic. Caffeine, acetaminophen and sulfamethoxazole were mitigated to a greater extent, whereas the removal of naproxen and carbamazepine was more limited. The appearance of epoxy-carbamazepine and N4-acetyl-sulfamethoxazole as possible TPs of carbamazepine and sulfamethoxazole, respectively, indicated that

  4. The automatic use of capillary isoelectric focusing with whole column imaging detection for carbamazepine binding to human serum albumin.

    Science.gov (United States)

    Maciążek-Jurczyk, Małgorzata; Pawliszyn, Janusz

    2016-08-01

    The binding of the anticonvulsant drug carbamazepine (CBZ) to human serum albumin, both without (dHSA) and in the presence of fatty acids (HSA) was studied in real time by capillary isoelectric focusing with whole column imaging detection (cIEF-WCID). Reaction mixtures at different CBZ:HSA and CBZ:dHSA molar ratios (0:1/25:1) were prepared in phosphate buffer saline (PBS) solution at a physiological pH (7.4), and incubated for 0-72h at 37°C in a water bath. Application of the cIEF-WCID method allowed for observations on the impact of increasing CBZ:serum albumin molar ratios on isoelectric point (pI) shifts, as well as changes in peak area and absorbance, which serve as evidence of structural alterations occurring in the protein in the presence of CBZ. The obtained cIEF-WCID results indicated that the dynamic process of complex formation is not dependent on incubation time. The presented work allowed for recognition of different types of interactions, as well as for the calculation of association constants that demonstrate the stability of the complex. This study was also designed to examine the possible impact of fatty acids (FAs) on protein stability and drug delivery in blood. PMID:26809616

  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. Efficient degradation of carbamazepine by easily recyclable microscaled CuFeO2 mediated heterogeneous activation of peroxymonosulfate.

    Science.gov (United States)

    Ding, Yaobin; Tang, Hebin; Zhang, Shenghua; Wang, Songbo; Tang, Heqing

    2016-11-01

    Microscaled CuFeO2 particles (micro-CuFeO2) were rapidly prepared via a microwave-assisted hydrothermal method and characterized by scanning electron microscopy, X-ray powder diffraction and X-ray photoelectron spectroscopy. It was found that the micro-CuFeO2 was of pure phase and a rhombohedral structure with size in the range of 2.8±0.6μm. The micro-CuFeO2 efficiently catalyzed the activation of peroxymonosulfate (PMS) to generate sulfate radicals (SO4-), causing the fast degradation of carbamazepine (CBZ). The catalytic activity of micro-CuFeO2 was observed to be 6.9 and 25.3 times that of micro-Cu2O and micro-Fe2O3, respectively. The enhanced activity of micro-CuFeO2 for the activation of PMS was confirmed to be attributed to synergistic effect of surface bonded Cu(I) and Fe(III). Sulfate radical was the primary radical species responsible for the CBZ degradation. As a microscaled catalyst, micro-CuFeO2 can be easily recovered by gravity settlement and exhibited improved catalytic stability compared with micro-Cu2O during five successive degradation cycles. Oxidative degradation of CBZ by the couple of PMS/CuFeO2 was effective in the studied actual aqueous environmental systems. PMID:27329789

  7. Interactions of valproic acid with carbamazepine and its metabolites' concentrations, concentrations ratios, and level/dose ratios in epileptic children.

    Science.gov (United States)

    Liu, H; Delgado, M R; Browne, R H

    1995-02-01

    In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10, 11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10, 11-dihydroxy-10, 11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = [formula: see text], respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA. PMID:8665529

  8. The association of C3435T single-nucleotide polymorphism, Pgp-glycoprotein gene expression levels and carbamazepine maintenance dose in patients with epilepsy

    Directory of Open Access Journals (Sweden)

    Sterjev Z

    2012-04-01

    Full Text Available Zoran Sterjev1, Gordana Kiteva Trencevska2, Emilija Cvetkovska2, Igor Petrov2, Igor Kuzmanovski2, Jasmina T Ribarska3, Aleksandra K Nestorovska1, Nadica Matevska1, Zorica Naumovska1, Suzana Jolevska-Trajkovic3, Aleksandar Dimovski1, Ljubica Suturkova11Institute of Pharmaceutical Chemistry, Faculty of Pharmacy Skopje, Republic of Macedonia; 2Clinic of Neurology, Faculty of Medicine, Skopje, Republic of Macedonia; 3Institute of Pharmaceutical Analysis, Faculty of Pharmacy Skopje, Republic of MacedoniaAbstract: The ABCB1 gene encodes the P-glycoprotein (Pgp protein, which is thought to transport various antiepileptic drugs. The single nucleotide polymorphism (SNP (C3435T in exon 26 of this gene correlates with the altered expression levels of P-glycoprotein, range of drug response and clinical conditions. In order to investigate the influence of this polymorphism on the susceptibility to and efficacy of carbamazepine therapy, we evaluated the allelic frequency and genotype distribution of this variant in 162 epilepsy patients from the Republic of Macedonia. Statistically significant differences were detected neither in the allelic frequency and genotype distribution between carbamazepine-resistant and carbamazepine-responsive epilepsy patients nor between the subgroups of carbamazepine (CBZ-responsive patients treated with different CBZ doses. However, the T-allele was enriched in CBZ-responsive patients who required higher maintenance CBZ doses, This observation was substantiated by the findings that the median total plasma levels were the lowest in patients with CC (20 µmol/L followed by CT (23 µmol/L and TT (29 µmol/L genotypes. Patients with a CC genotype also had a higher likelihood of response compared to patients with CT or TT genotypes over a wide range (400–1000 mg/day of initial doses of CBZ. The T allele showed a reduced expression of ~5% compared to the C allele in peripheral blood mononuclear cells in heterozygotes for the variant

  9. Structural modeling of HLA-B*1502/peptide/carbamazepine/T-cell receptor complex architecture: implication for the molecular mechanism of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

    Science.gov (United States)

    Zhou, Peng; Zhang, Shilei; Wang, Yewang; Yang, Chao; Huang, Jian

    2016-08-01

    Drug-induced adverse reactions are a significant problem in healthcare worldwide and are estimated to cost billions of dollars annually in the United States. A portion of such reactions is observed to strongly associate with certain human leukocyte antigen (HLA) alleles; one of the strongest associations is the HLA-B*1502 protein with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) - the odds ratio value can even be higher than one thousand. The particularly strong association in CBZ-induced SJS/TEN suggests that the HLA-B*1502 is not only a genetic marker but also a participant in the pathogenesis of the disease. In the current study, we attempt to computationally model the atomic-level structure of the complete HLA-B*1502/peptide/CBZ/T-cell receptor (TCR) complex architecture based on prior knowledge obtained from epidemiological investigations as well as in vitro and in vivo assays. The model tells a different story about the molecular mechanism of CBZ-induced SJS/TEN from that previously reported for abacavir (ABC)-induced hypersensitivity (HSR); the CBZ molecule is located at the interface between HLA-B*1502/peptide and TCR, directly contacts the P3-P6 residues of antigen peptide, and bound within a pocket region encompassed by two TCR CDR3 fingers. Molecular dynamics simulation and binding energy analysis further reveal that the CBZ shows considerably high affinity to TCR over HLA-B*1502/peptide, which can tightly interact with the former rather than the latter. From the model, two hypotheses are proposed that can well explain most previous observations and are expected to guide next wet-lab experiments. This study could help to promote our understanding of the molecular mechanism and pathological implication underlying CBZ-induced SJS/TEN. PMID:26488421

  10. 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.

  11. Regenerable granular carbon nanotubes/alumina hybrid adsorbents for diclofenac sodium and carbamazepine removal from aqueous solution.

    Science.gov (United States)

    Wei, Haoran; Deng, Shubo; Huang, Qian; Nie, Yao; Wang, Bin; Huang, Jun; Yu, Gang

    2013-08-01

    A novel granular carbon nanotubes (CNTs)/alumina (Al2O3) hybrid adsorbent with good sorption and regeneration properties was successfully prepared by mixing CNTs with surfactant Brij 35 and pseudo boehmite, followed by calcining to remove surfactant and form porous granules. Alumina binder increased the mechanical strength, hydrophilicity and porosity of the granular adsorbent, while the dispersed CNTs in the granular adsorbent were responsible for the sorption of diclofenac sodium (DS) and carbamazepine (CBZ). Scanning electron microscopy (SEM) showed that the CNTs and Al2O3 were mixed well and the porous structure was formed in the granular adsorbent. The high surface area and appropriate pore size of granular CNTs/Al2O3 adsorbent were favorable for sorption. The sorption of DS decreased with increasing solution pH, while pH had little effect on CBZ sorption. The maximum sorption capacities of CBZ and DS on the CNTs/Al2O3 adsorbent were 157.4 and 106.5 μmol/g according to the Langmuir fitting. Moreover, the spent CNTs/Al2O3 adsorbent can be thermally regenerated at 400 °C in air due to the thermal stability of CNTs. The removal of CBZ and DS changed a little in the initial reuse cycles and then kept relatively constant until tenth cycles. The adsorbed CBZ and DS were decomposed in the regeneration process. This regenerable adsorbent may find potential application in water or wastewater treatment for the removal of some micropollutants such as pharmaceuticals. PMID:23579087

  12. Practical guidance and considerations for transitioning patients from oxcarbazepine or carbamazepine to eslicarbazepine acetate--Expert opinion.

    Science.gov (United States)

    Peltola, Jukka; Holtkamp, Martin; Rocamora, Rodrigo; Ryvlin, Philippe; Sieradzan, Kasia; Villanueva, Vicente

    2015-09-01

    There is currently a lack of guidance on methodology and special considerations for transitioning patients from oxcarbazepine (OXC) or carbamazepine (CBZ) to eslicarbazepine acetate (ESL), if deemed clinically necessary. An advisory panel of epilepsy experts was convened to share their experience on the use of adjunctive ESL in clinical practice and to provide practical recommendations to help address this gap. When changing over from OXC to ESL, an OXC:ESL dose ratio of 1:1 should be employed to calculate the ESL target dose, and the changeover can take place overnight. No changes to comedication are required. Since CBZ has a different mechanism of action to ESL and is a stronger inducer of cytochrome P450 (CYP) enzymes, the transitioning of patients from CBZ to ESL requires careful consideration on a patient-by-patient basis. In general, a CBZ:ESL dose ratio of 1:1.3 should be employed to calculate the ESL target dose, and patients should be transitioned over a minimum period of 1-2weeks. Special considerations include adjustment of titration schedule and target dose in elderly patients and those with hepatic or renal impairment and potential adjustment of comedications metabolized by CYP enzymes. In summary, due to structural distinctions between ESL, OXC, and CBZ, which affect mechanism of action and tolerability, there are clinical situations in which it may be appropriate to consider transitioning patients from OXC or CBZ to ESL. Changing patients over from OXC to ESL is generally more straightforward than transitioning patients from CBZ to ESL, which requires careful consideration. PMID:26114438

  13. Prophylactic efficacy of lithium, valproic acid, and carbamazepine in the maintenance phase of bipolar disorder: a naturalistic study.

    Science.gov (United States)

    Peselow, Eric D; Clevenger, Steven; IsHak, Waguih W

    2016-07-01

    Mood stabilizers are used clinically for the management of bipolar disorder. Prophylactic therapy with mood stabilizers is the primary treatment for preventing depressive and manic relapses in bipolar patients once they are stabilized. In this study, we examined the relative efficacy of the three most commonly used mood-stabilizing agents: lithium (Li), valproic acid (VPA), and carbamazepine (CBZ), in preventing relapse episodes. A total of 225 patients with bipolar disorder were included in the present analysis. Patients taking Li, VPA, or CBZ were followed up for up to 124 months, until suffering a manic, mixed, or depressive episode (relapse), or until the end of the study/study termination (no relapse), whichever came first. The median unadjusted survival time was 36 months for patients taking VPA, 42 months for patients taking CBZ, and 81 months for patients taking Li. These results indicate that patients stayed longer on Li, suggesting that it might have been better tolerated than either CBZ or VPA. χ-Analysis showed that patients taking Li were significantly less likely to experience relapse during the observational period than patients taking either VPA or CBZ (P<0.05). A Cox regression model showed that the hazard of experiencing relapse was significantly predicted by the total number of depressive (P=0.007) and manic symptoms (P=0.02) assessed before the observation period. In addition, after controlling for symptom covariates, the hazard of experiencing relapse was 1.66 times (95% confidence interval 1.03-2.67) or 66% higher for patients taking VPA compared with patients taking Li (P=0.037). Although the hazard of experiencing relapse was higher for patients taking CBZ compared with those taking Li, the risk was not elevated by a significant amount. Notwithstanding the limitations of the naturalistic design of this study, the differences in relapse prevention and survival time observed in these medications show Li fairing relatively better in

  14. Carbamazepine behaviour and effects in an urban wastewater MBR working with high sludge and hydraulic retention time.

    Science.gov (United States)

    González-Pérez, Daniel María; Pérez, Jorge Ignacio; Nieto, Miguel Ángel Gómez

    2016-08-23

    The behaviour and fate of carbamazepine (CBZ) in urban wastewater treatment by a membrane bioreactor (MBR) and its possible effects on the system's efficiency, and on mixed microbial communities, has been studied. The experimental microfiltration MBR system, with capacity to treat 10.8 m(3) d(-1) of urban wastewater, operated with a pre-denitrification configuration with high sludge and hydraulic retention time. The CBZ concentration assayed was higher than in the usual urban wastewater, in order to provoke a strong biomass reaction. Influent, effluent, and all bioreactors of the MBR system were analysed in order to calculate a CBZ balance. Bench-scale experiments and respirometric analyses were performed, with and without the presence of CBZ, to evaluate its influence on the bacterial activity. The respirometric assays showed variations in the oxygen uptake rate (OUR) in the presence of CBZ. Negative effects were detected in the MBR bacterial community during the initial period of dosing. However, the effects were not permanent and the biomass spiked with CBZ had behaviour similar to that of the biomass without CBZ after a few hours. Biodegradation was not detected during the MBR treatment. The system showed an inefficient elimination of CBZ (less than 10%) with a high concentration in the effluent. The small percentage of CBZ removal was associated with the sludge retention and eliminated by the purge. All CBZ present in the influent was accounted for, and even an increase in the total amount of CBZ was registered in the permeate. During and after the experimental process, CBZ did not significantly affect the efficiency of the MBR system, and the quality of the effluent was not affected by the dosing of CBZ in terms of COD and nitrogen removal. PMID:27230859

  15. Intravenous immunoglobulin in the treatment of primary trigeminal neuralgia refractory to carbamazepine: a study protocol[ISRCTN33042138

    Directory of Open Access Journals (Sweden)

    Roewer Norbert

    2003-01-01

    Full Text Available Abstract Background We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin (IVIG in a prospective, open-label cohort study. A randomised, placebo controlled, double blinded study is needed to confirm these results. We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia (rpTN, as these had responded particularly well to IVIG. A protocol involving the use of IVIG in rpTN is complex for three reasons: 1. The effect of IVIG does not follow simple dose-response rules; 2. The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and >1 year; 3. TN is characterized by extremely severe pain, for which operative intervention is (if temporarily helpful in most patients. Design A placebo controlled, parallel, add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study. Study groups are compared using Kaplan-Maier survival analysis. Patients record their response to treatment ("severe, moderate, slight, no pain". The study coordinator monitors pain diaries. Severe or moderate pain of three days duration will result in termination of the study for that patient. Conclusions This study design utilizes a method of survival analysis and is novel in chronic pain research. It allows for both early departure from the study and voluntary crossover upon non-response. It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes.

  16. Effects of carbamazepine and two of its metabolites on the non-biting midge Chironomus riparius in a sediment full life cycle toxicity test.

    Science.gov (United States)

    Heye, Katharina; Becker, Dennis; Lütke Eversloh, Christian; Durmaz, Vedat; Ternes, Thomas A; Oetken, Matthias; Oehlmann, Jörg

    2016-07-01

    The antiepileptic drug carbamazepine (CBZ) and its main metabolites carbamazepine-10,11-epoxide (EP-CBZ) and 10,11-dihydro-10,11-dihydroxy-carbamazepine (DiOH-CBZ) were chosen as test substances to assess chronic toxicity on the non-biting midge Chironomus riparius. All the three substances were tested in a 40-day sediment full life cycle test (according to OECD 233) in which mortality, emergence, fertility, and clutch size were evaluated. In addition, these parameters were considered to calculate the population growth rate which represents an integrated measure to assess population relevant effects. With an LC50 of 0.20 mg/kg (time-weighted mean), the metabolite EP-CBZ was significantly more toxic than the parent substance CBZ (LC50: 1.1 mg/kg). Especially mortality, emergence, and fertility showed to be sensitive parameters under the exposure to CBZ and EP-CBZ. By using classical molecular dynamics (MD) simulations, the binding of CBZ to the ecdysone receptor was investigated as one possible mode of action (MoA) but appeared to be unlikely. The second metabolite DiOH-CBZ did not cause any effects within the tested concentration rage (0.17-1.2 mg/kg). Even though CBZ was less toxic compared to EP-CBZ, CBZ is found in the environment at much higher concentrations and therefore causes a higher potential risk for sediment dwelling organisms compared to its metabolites. Nevertheless, the current study illustrates the importance of including commonly found metabolites into the risk assessment of parent substances. PMID:27064208

  17. Entwicklung und Validierung eines Enzyme-linked Immunosorbent Assays (ELISA) für die Quantifizierung von Carbamazepin in Abwasser, Oberflächenwasser und Trinkwasser

    OpenAIRE

    Bahlmann, Arnold

    2013-01-01

    Ein kompetitiver ELISA (Enzyme-linked Immunosorbent Assay) für den Nachweis von Carbamazepin (CBZ) mit einer Bestimmungsgrenze von ca. 30 ng/L wurde entwickelt und validiert. Dieser in Gewässern häufig auftretende anthropogene Marker wurde anschließend in einer Vielzahl an Proben aus Abwässern, Oberflächengewässern und Trinkwässern nachgewiesen. Der ELISA zeigte eine exzellente Präzision und erbrachte in allen Matrizes geringfügig höhere Analysenergebnisse als die Referenzmethode HPLC-MS/MS. ...

  18. Efficacy of carbamazepine combined with mestilate in treatment of vestibular paroxysmia%卡马西平联合敏使朗治疗前庭阵发症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    李建辉

    2013-01-01

    Objective:To evaluate the clinical efficiency of carbamazepine combined with mestilate for treatment of vestibular paroxys -mia.Methods:Eighty-six patients suffering from vestibular paroxysmia were underwent the research , they were randomly divided into two groups, the carbamazepine combined with mestilate group (43case) and the carbmazepine group(43case), the efficacy of the two groups were observed .Results:The efficiency rate in the carbamazepine combined with mestilate group was higher than the carbamazepine group (P<0.05).The side effects of carbamazepine combined with mestilate group were generally mild .Conclusion:Carbamazepine combined with mestilate in treatment of vestibular paroxysmia had good clinical curative effect , highly safety , should be worth clinical use.%目的:观察和探讨卡马西平联合敏使朗治疗前庭阵发症的临床疗效。方法:选取2010年9月~2012年2月经我院眩晕门诊诊断的前庭阵发症患者86例,将患者随机分为卡马西平联合敏使朗组(43例)和卡马西平组(43例),观察2组的疗效。结果:卡马西平联合敏使朗组的有效率高于卡马西平组,差异有统计学意义(P<0,05),而且不良反应少。结论:卡马西平联合敏使朗治疗前庭阵发症的临床疗效好、安全性高,值得临床推广使用。

  19. 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. PMID:27105033

  20. 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.

  1. Biodegradation of carbamazepine and clarithromycin by Trichoderma harzianum and Pleurotus ostreatus investigated by liquid chromatography - high-resolution tandem mass spectrometry (FTICR MS-IRMPD).

    Science.gov (United States)

    Buchicchio, Alessandro; Bianco, Giuliana; Sofo, Adriano; Masi, Salvatore; Caniani, Donatella

    2016-07-01

    In this study, the capability of pharmaceutical biodegradation of fungus Trichoderma harzianum was evaluated through the comparison with the well-known biodegradation capability of white-rot fungus Pleurotus ostreatus. The study was performed in aqueous phase under aerobic conditions, using two of the most frequently detected drugs in water bodies: carbamazepine and clarithromycin, with concentrations commonly found in treated wastewater (4μg/l and 0.03μg/l respectively). For the first time, we demonstrated that T. harzianum is able to remove carbamazepine and clarithromycin. The analyses were performed by reversed-phase liquid chromatography/mass spectrometry, using high-resolution Fourier-transform ion cyclotron resonance mass spectrometry upon electrospray ionization in positive ion mode. The high selectivity and mass accuracy provided by high-resolution mass spectrometry, allowed us to identify some unknown metabolites. On the basis of our study, the major metabolites detected in liquid culture treated by T. harzianum were: 14-hydroxy-descladinosyl- and descladinosyl-clarithromycin, which are pharmacologically inactive products not dangerous for the environment. PMID:27039063

  2. 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

  3. 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.

  4. 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.

  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. 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)

    Boetker, Johan P.; Rantanen, Jukka; Arnfast, Lærke;

    2016-01-01

    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...... 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...... 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...

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

    International Nuclear Information System (INIS)

    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 14C-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

  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. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

    OpenAIRE

    Findling RL; Ginsberg LD

    2014-01-01

    Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC) in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17&nbs...

  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. A comprehensive study of the relation between serum concentrations, concentration ratios, and level/dose ratios of carbamazepine and its metabolites with age, weight, dose, and clearances in epileptic children.

    Science.gov (United States)

    Liu, H; Delgado, M R

    1994-01-01

    We made a comprehensive study of the relation between age, weight, carbamazepine (CBZ) dose, total clearance (TC), and intrinsic clearance (IC) and concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11- dihydro-carbamazepine (CBZ-H) in a group of epileptic children receiving CBZ monotherapy. Body weight and age showed negative correlations with TC, IC, CBZ dose, and CBZ-E/CBZ and CBZ-H/CBZ concentration ratios, and had positive relation with CBZ, CBZ-E, and CBZ-H level/dose ratios. These results indicate decreased CBZ metabolism with patient maturity. Correlations between CBZ dose with TC, IC, and the concentration ratios of CBZ-E/CBZ, CBZ-H/CBZ-E, and CBZ-H/CBZ were positive. CBZ dose also had negative associations with CBZ and CBZ-E level/dose ratios, indicating dose-dependent autoinduction of CBZ metabolism. Our data suggest that weight, age, and CBZ dose have less influence on epoxide-hydrolase activities than on epoxidase activities. The CBZ-E/CBZ concentration ratio can be used as an indicator of the degree of autoinduction of CBZ metabolism, even in patients receiving CBZ monotherapy. PMID:7988515

  13. 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.

  14. Carbamazepine transbuccal delivery: the histo-morphological features of reconstituted human oral epithelium and buccal porcine mucosae in the transmucosal permeation.

    Science.gov (United States)

    Campisi, G; Paderni, C; Saccone, R; Siragusa, M G; Lo Muzio, L; Tripodo, C; Giannola, L I; Florena, A M

    2008-01-01

    Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer. PMID:19144275

  15. 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.

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

    Science.gov (United States)

    Al-Rajab, Abdul Jabbar; Sabourin, Lyne; Lapen, David R; Topp, Edward

    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 (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. PMID:25644844

  17. Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice

    Directory of Open Access Journals (Sweden)

    Ranjana I Brahmane

    2010-01-01

    Full Text Available Objective: To study the effect of calcium channel blockers (CCBs cinnarizine and nifedipine on maximal electroshock (MES-induced and pentylenetetrazole (PTZ-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED. Materials and Methods: For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg, nifedipine (5 mg/kg, sodium valproate (300 mg/kg and carbamazepine (8 mg/kg alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher′s exact test (Ovvind Langsrud software, German version. Results: In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures. Conclusion: The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.

  18. 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.

  19. 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.

  20. 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.

  1. Immediate and delayed treatment with gabapentin, carbamazepine and CNQX have almost similar impact on cognitive functions and behavior in the lithium-pilocarpine model in rats.

    Science.gov (United States)

    Gulec Suyen, Guldal; Isbil-Buyukcoskun, Naciye; Kahveci, Nevzat; Sengun, Ece; Ozluk, Kasim

    2016-09-01

    In the present study, we aimed to investigate the effects of immediate and delayed treatment with intracerebroventricular (i.c.v.) gabapentin (GBP), carbamazepine (CBZ) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on learning and memory, anxiety, and locomotor activity in rats with lithium-pilocarpine-induced status epilepticus (SE). SE was induced by intraperitoneal injections of 3mEq/kg LiCl followed by 45mg/kg pilocarpine 24h later. In the first series of experiments, rats were divided into four groups three hours after the onset of SE and received GBP (100μg/10μl, two times a day; i.c.v.), CBZ (200μg/10μl; i.c.v.), CNQX (25nmol/10μl; i.c.v.) or saline (10μl; i.c.v.) for 7days. Six weeks after SE, cognitive and behavioral performances were evaluated by Morris water maze, elevated plus maze, and open field tests. In the second series, rats received no treatment for six weeks following SE. On the seventh week the same treatment with the previous rats was given and six weeks later the cognitive and behavioral tests were applied. SE significantly impaired spatial learning and memory in the Morris water maze. GBP treatment improved the acqusition and memory performance. CNQX worsened the acqusition but improved the memory performance, while CBZ worsened both parameters. In the elevated plus maze, epileptic rats which received saline showed significantly lower anxiety levels with respect to the naive rats. Only CBZ led to further anxiolysis, while the other drugs had no effect. Locomotor activity significantly increased due to SE, which was augmented by GBP and CNQX. The impact of immediate and delayed treatment with these drugs on cognition and behavior seems to be quite similar. PMID:27426469

  2. 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

  3. 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.

  4. Visualizing the conversion of carbamazepine in aqueous suspension with and without the presence of excipients: a single crystal study using SEM and Raman microscopy.

    Science.gov (United States)

    Tian, F; Sandler, N; Gordon, K C; McGoverin, C M; Reay, A; Strachan, C J; Saville, D J; Rades, T

    2006-11-01

    Visual observations of the hydration process of single carbamazepine (CBZ) crystals in water and in various excipient solutions [(1% w/v) - hydroxypropyl cellulose (HPC), poly(vinyl pyrrolidone) (PVP), sodium carboxymethylcellulose (CMC) at pH 7.5 and 3.0, and polyethylene glycol (PEG)] using scanning electron microscopy (SEM) are reported in this paper. Raman microscopy was used to confirm the chemical structures of the unconverted CBZ and the CBZ dihydrate (DH) needles. It was found that defect structures were a more important driving force than the nature of crystal faces for the initiation of the hydration, but face differences became obvious after 6 h immersion. The biggest crystal face grown from methanol, (100), was the slowest one to be covered with DH needles. A comparison of the molecular arrangements along the three crystal faces [(100), (010) and (001)] was carried out using crystal structure visualization software, and fewer polar groups exposed on the (100) face than on the (001) and (010) faces were found, explaining the comparatively weak interaction of the (100) face with water during hydration. Furthermore, investigation of the influence of excipients on the hydration of CBZ showed that both HPC and PVP strongly inhibited conversion, and no conversion of CBZ to DH was found after 18 h immersion in water. PEG and CMC (pH 7.5) were less potent inhibitors than HPC and PVP, and DH needles were observed on all the faces except the (100) face after 18 h immersion. No conversion was detected for the crystal immersed in CMC solution at pH 3.0. This is likely to be caused by the decreased polarity of CMC in water at pH 3.0 (pKa,cmc = 4.3), and thus a higher surface adsorption of CMC to the CBZ crystals in dispersion. The influence of excipients on the conversion of CBZ observed in this study agreed well with our previous quantitative studies using Raman spectroscopy. In this study, visual observation using electron microscopy has been demonstrated to be a

  5. 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

  6. 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.

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

    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

  8. A chiral HPLC-UV method for the quantification of dibenz[b,f]azepine-5-carboxamide derivatives in mouse plasma and brain tissue: eslicarbazepine acetate, carbamazepine and main metabolites.

    Science.gov (United States)

    Fortuna, Ana; Bicker, Joana; Alves, Gilberto; Falcão, Amílcar; Soares-da-Silva, Patrício

    2011-06-01

    For the first time, a selective and sensitive chiral HPLC-UV method was developed and fully validated for the simultaneous quantification of eslicarbazepine acetate (ESL), carbamazepine (CBZ), S-licarbazepine (S-Lic), R-licarbazepine (R-Lic), oxcarbazepine (OXC) and carbamazepine-10,11-epoxide (CBZ-E), in mouse plasma and brain homogenate supernatant. After the addition of chloramphenicol as the internal standard, samples were processed using an SPE procedure. The chiral chromatographic analysis was carried out on a LiChroCART 250-4 ChiraDex column, employing a mobile phase of water and methanol (88:12, v/v) pumped at 0.9 mL/min and the UV detector set at 235 nm. The assay was linear (r(2) ≥0.995) for ESL, CBZ, OXC, S-Lic, R-Lic and CBZ-E in the range of, respectively, 0.2-4, 0.4-30, 0.1-60, 0.2-60, 0.2-60 and 0.2-30 μg/mL, in plasma, and of 0.06-1.5 μg/mL for ESL, 0.12-15 μg/mL for CBZ and CBZ-E and 0.06-15 μg/mL for OXC and both licarbazepine (Lic) enantiomers in brain homogenate supernatant. The overall precision was within 8.71% and accuracy ranged from -7.55 to 8.97%. The recoveries of all the compounds were over 92.1%. Afterwards, the application of the method was demonstrated using real plasma and brain samples obtained from mice administered simultaneously with ESL and CBZ. PMID:21557472

  9. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

    Directory of Open Access Journals (Sweden)

    Findling RL

    2014-08-01

    Full Text Available Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200–1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS.Results: A total of 60 children (ages 10–12 and 97 adolescents (ages 13–17, with an overall average age of 13.4 years (standard deviation [SD] 2.0 years received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days, with 66 (42% completing the entire study. At end of study participation (end point, the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2 at baseline to a mean of 13.8 (SD 9.4 (P<0.0001 at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6, white blood cell count decreased (n=5, nausea (n=3, and vomiting (n=3. No deaths were reported. The most commonly reported AEs were headache (n=41, somnolence (n=30, nausea (n=22, dizziness (n=21, and fatigue (n=19.Conclusions: Open-label administration of ERC might be a safe

  10. 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.

  11. 非卡马西平所致药疹与 HLA -B*1502基因型相关性研究%Study on the correlation of drug eruption caused by non -carbamazepine antiepileptics and genotype of HLA-B*1502

    Institute of Scientific and Technical Information of China (English)

    武美艳; 侯春风; 李军; 李保敏

    2015-01-01

    Objective To discuss the correlation of drug eruption caused by non -carbamazepine antiepileptics and genotype of HLA-B*1502. Methods The genotype of HLA -B*1502 of patients, including 26 cases of drug eruptions caused by non -carbamaz-epine antiepileptics and 8 cases caused by carbamazepine , were detected in peripheral blood by the PCR -SS0 probe.Results There were 26 patients in the group of non -carbamazepine administration .The expres-sion of HLA-B*1502 gene was positive in 1 case and negative in 14 ca-ses in the group of oxcarbazepine administration;the expression was neg-ative in all the 3 cases in the group of lamotrigine administration , the ex-pression was negative in all the 3 cases in the group of levetiracetam ad-ministration , the expression was negative in both of the 2 cases in the group of phenytoinum administration , the expression was negative in both the 2 cases in the group of phenobarbital administration , and the expres-sion was negative in 1 cases in the group of valproate administration . There were 8 patients in the group of carbamazepine administration .The expression of HLA-B*1502 gene was positive in 5 cases and negative in 3 cases.Patients with drug eruption caused by antiepileptic drugs all changed the administration .The result showed that the positive expression rate of HLA-B*1502 gene was lower in the group of non-carbamazepine administration than that in the group of carbamazepine administration ( P<0.05 ).Con-clusion There was no correlation between the drug eruption caused by non -carbamazepine administration and the genotype of HLA-B*1502.Carbamazepine can be switched , if necessary , in cases who have drug eruption caused by administration of non -carbamazepine antiepileptics .%目的:评价非卡马西平抗癫痫药所致药疹与HLA-B*1502基因型的相关性。方法用PCR-SS0探针法测定26例非卡马西平抗癫痫药物药疹的患者及8例用卡马西平药疹的患者外周血白细胞HLA-B*1502

  12. 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

  13. 甲钴胺联合卡马西平治疗三叉神经痛的效果观察%Clinical observation of mecobalamin combined with carbamazepine in treatment of trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    徐立; 张友章; 陈刚

    2014-01-01

    Objective To investigate the clinical efficacy of mecobalamin combined with carbamazepine in treatment of trigeminal neuralgia.Methods A total of 180 patients with trigeminal neuralgia from No.113 Hospital of People's Liberation Army were gathered from March 2011 to March 2012.They were randomly divided into control group and study group.The control group received carbamazepine (0.1 g,bid.) and the study group received mecobalamin (0.5 mg,tid.) on the basis of the control group.The visual analogue scale(VAS) score and quality of life scores,pain relief and other adverse reactions were compared after two weeks,four weeks and eight weeks,respectively.Results The VAS scores were significantly different in the two groups after 2,4 and 8 weeks [study group:(4.0±1.8) scores,(2.4±0.7) scores,(1.0±1.1) scores; control group:(4.3±1.7) scores,(3.1 ±0.8) scores,(1.8 ±0.9) scores] (all P < 0.05).The cases with complete remission in study group[68.9% (62/90)]were significantly higher than those in the control group[54.4% (49/90)] (P <0.05).The scores of sleep,life,appetite and interest in study group [(2.1 ± 0.3) scores,(2.7 ± 0.9) scores,(2.4 ± 0.2) scores,(2.9 ± 0.5) scores] were significantly lower than those in the control group [(4.3 ± 0.9) scores,(7.1 ± 1.4) scores,(6.3 ±0.6) scores,(6.9 ± 1.1) scores] (all P < 0.05).The adverse effects rates were no significantly different in the two groups[2.2% (2/90) vs 8.9% (8/90),P >0.05].Conclusion Mecobalamin combined with carbamazepine for the treatment of trigeminal neuralgia can relieve pain significantly and improve the quality of life.%目的 探讨甲钴胺联合卡马西平治疗三叉神经痛的临床疗效.方法 选取2011年3月至2012年3月解放军第一一三医院收治的180例原发性三叉神经痛患者,采用随机数字表法分为研究组和对照组,每组90例.对照组患者服用卡马西平片(0.1g/次,2次/d);研究组在对照组的基础上加服甲钴胺片(0.5 mg

  14. 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

  15. 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.

  16. 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.

  17. 卡马西平对癫(痫)患者血浆纤维蛋白原含量的影响%Effect of Carbamazepine on plasma fibrinogen for epilepsy patients

    Institute of Scientific and Technical Information of China (English)

    刘广韬; 潘隆盛; 凌至培; 许百男

    2011-01-01

    目的 分析口服卡马西平(CBZ)对患者血浆纤维蛋白原含量的影响.方法 回顾性分析我院收治的使用卡马西平出现血浆纤维蛋白原含量降低患者的临床资料,对患者的性别,年龄、卡马西平的用法用量、用药时间、停药时间、停药前后纤维蛋白原的含量变化及转归进行分析讨论.结果 12例男性患者均为长期不规则服药,时长与病史年限大致相同.经停用卡马西平,11例患者纤维蛋白原恢复至2.0 g/L以上,1例停药14 d,纤维蛋白原由1.40g/L升至1.92g/L.结论 卡马西平可致患者血浆纤维蛋白原含量降低,用药过程中应监测纤维蛋白原含量,以防引起严重出血.%Objective To analyze the effect of oral administration with Carbamazepine (CBZ) on plasma fibrinogen content for epilepsy patients. Methods The clinical data of patients with CBZ reduced plasma fibrinogen levels in patients were analyzed retrospectively. The patient's sex, age,use of CBZ dosage, administration time, stop medicine time, fibrinogen levels before and after drug withdrawal and the prognosis were analyzed and compared. Results 12 male patients in long-term irregular medication, whose duration and medical history were approximately same. The disabled and symptomatic treatment of CBZ, 11 patients recovered to fibrinogen 2.0 g/L or more, one case of withdrawal 14 d and fibrinogen by the 1. 40 g/L increased to 1.92 g/L. Conclusion CBZ may cause decreased plasma fibrinogen levels, should be monitored during the medication, to prevent serious bleeding.

  18. Fate of Carbamazepine during Water Treatment

    DEFF Research Database (Denmark)

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

    2009-01-01

    of acridone, hydroxy-(9H,10H)-acridine-9-carbaldehyde, acridone-N-carbaldehyde, and 1-(2-benzaldehyde)-(1H,3H-quinazoline-2,4-dione, while biological breakdown of acridine yielded acridone. In parallel, the transformation product iminostilbene was observed during sample analysis. In addition,this study...

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 调神活血止痛针刺法与卡马西平治疗丘脑痛作用特点的动态变化观察%Dynamic Observation on Therapeutic Features of Thalamic Pain by Mind Calming, Blood Activating and Pain Relief Acupuncture and Carbamazepine

    Institute of Scientific and Technical Information of China (English)

    樊小农; 张雪; 武连仲; 王海荣

    2011-01-01

    Objective To observe therapeutic features of thalamic pain by mind Calming, blood activating and pain relief acupuncture and Carbamazepine.Methods Crossover trial design was adopted.Eleven patients with confirmed diagnosis of thalamic pain were randomly assigned to two groups according to the minimal unbalance index method, i.e., Group Ⅰ ( Six patients received acupuncture first and then Western medicine.) and Group Ⅱ ( Five patients received Western medicine first and then acupuncture).The therapeutic course for each group was ten days.There was a ten-day elution phase between the two therapeutic methods.The total therapeutic course was thirty days.Eleven patients were enrolled in the two groups for statistical analysis.The therapeutic efficacy was assessed with visual analogue scale (VAS) and the pain assessment scale of Anderson Cancer Center in the USA (MD Pain Evaluation value) respectively.The VAS and MD values of the two groups were recorded every day to get the dynamic curve.Results The VAS and MD values obviously decreased in the two groups after treatment (P<0.05).The pain curves of the two groups showed a declining trend during the treatment.A gradual and stable descending process was shown in the acupuncture group.But a greater decrease first appeared in the Western medicine group, then a comparatively greater decrease occurred after one platform stage, showing ladder-shaped curve.Conclusions Cumulative potency may be the main analgesic effects of acupuncture.Western medicine may possibly play a role by rapid initiate effect.%目的 观察调神活血止痛针刺法与卡马西平治疗丘脑痛的作用特点.方法 采用交叉试验设计,将11例确诊患者按最小不平衡指数法随机分为1组(先针刺治疗后西药治疗6例)和2组(先西药治疗后针刺治疗5例).每种疗法疗程10天,两种方法间有10天洗脱期,总疗程30天.进行统计分析时,针刺组和西药组均为11例.分别应用视觉模拟评分法(VAS)

  4. Determination of the Phenobarbitone(PBB),Carbamazepine(CBM),Estazolam (ETZ),Alprazolam(APZ),Clonazepam(CZP) and Oxazepam (OZP) concentration in the human plasma by HPLC%高效液相色谱法同时测定苯巴比妥、卡马西平、艾司唑仑、阿普唑仑、氯硝西泮、奥沙西泮的血药浓度

    Institute of Scientific and Technical Information of China (English)

    徐晖

    2013-01-01

    目的 建立高效液相色谱法同时测定苯巴比妥(Phenobarbitone PBB)、卡马西平(Carbamazepine CBM)、艾司唑仑(Estazolam ETZ)、阿普唑仑(Alprazolam APZ)、氯硝西泮(Clonazepam CZP)、奥沙西泮(Oxazepam OZP)等血药浓度.方法 取血浆样品在pH=8.0磷酸盐缓冲液条件下用乙酸乙酯和石油醚混合溶剂提取后在55℃水浴氮气中吹干,残渣用甲醇-水(55:45)溶解后进样分析,流动相为甲醇:磷酸盐缓冲液(55:45 pH=3.0),柱温31℃,检测波长230nm,流速0.9mL·min-1.结果 苯巴比妥、卡马西平分别在0.5~100μg·mL-1、0.2~40μg·mL-1,其他组分均在0.02~4.0μg·mL-1范围内浓度与峰面积线性关系良好.日内和日间差均小于5%,回收率均在97.3%~102.8%,最低检测浓度(S/N≥3):苯巴比妥20ng·mL-1,卡马西平5ng·mL-1,其余组分均10ng·mL-1.结论 本法操作简便,结果准确,适用于临床常规血药浓度检测.

  5. Predicted environmental concentrations of carbamazepine, oxcarbazepine and their main metabolites in a coastal system

    OpenAIRE

    Fenet, Helene; Arpin-pont, Lauren; Vanhoutte Brunier, Alice; Munaron, Dominique; Fiandrino, Annie; Hilaire-buys, Dominique; Mathieu, Olivier; BUDZINSKI Helene; Chiron, Serge; Boillot, Clotilde; Gomez, Elena

    2012-01-01

    Pharmaceuticals are widely released in aquatic environment through treated wastewaters. They reach coastal zone indirectly via streams or directly though marine outfalls however data concerning this contamination in coastal waters are scarce. Environmental Risk Assessment (ERA) of pharmaceuticals have been conducted mostly in surface waters and has not been performed in coastal zone. The first step of ERA is to evaluate the exposure through predictive environmental concentration (PEC) valu...

  6. Spatial Distribution of the Human Drug Carbamazepine in a Constructed Wetland Receiving Municipal Sewage Eflluent

    Science.gov (United States)

    Artificially constructed wetlands offer a low cost treatment alternative to remove a number of pollutants found in effluent water from industry, mining, agriculture, and urban areas. Wetlands can be used to mechanically remove suspended solids through sedimentation. Dissolved nutrients, biochemica...

  7. [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.

  8. 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

  9. Design and start-up of laboratory scale membrane bioreactor for biological degradation of ibuprofen, diclofenac and carbamazepine

    OpenAIRE

    Riska, Mats

    2016-01-01

    Pharmaceuticals and their fate in the wastewater treatment is a growing area of interest among researchers. Some pharmaceuticals are removed during conventional active sludge process, but new advanced methods are needed to improve the effluent quality. MBR (Membrane Bioreactor) technology is one of the fastest growing new technologies that can be used to receive better effluent quality. In this thesis two parallel laboratory scale MBR wastewater treatment plants were designed and built. T...

  10. 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.

  11. 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.

  12. A Control Study of Clonazepam and Carbamazepine in the Treatment of Manic Episodes%氯硝西泮与卡马西平治疗躁狂发作临床观察

    Institute of Scientific and Technical Information of China (English)

    高丽红; 路光辉

    2002-01-01

    目的:评价氯硝西泮与卡马西平对锂盐治疗无效的躁狂发作的疗效和副反应.方法:将符合CCMD-2-R躁狂发作诊断标准的72例患者随机分为氯硝西泮组(35例)和卡马西平组(37例),治疗6周.使用Bech-Rafaelsen躁狂量表及临床疗效总评量表评定疗效,用副反应量表及有关实验室检查评定副反应.结果:氯硝西泮与卡马西平均能有效减轻躁狂症状,疗效相近,卡马西平起效时间迟于氯硝西泮.氯硝西泮和卡马西平的副反应均以共济失调、头晕、嗜睡多见.结论:氯硝西泮与卡马西平均可用于锂盐治疗无效的躁狂发作,疗效相当.

  13. 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.

  14. 丙戊酸钠、卡马西平对首发躁狂患者体质量及瘦素的影响%Valproate sodium and Carbamazepine induced weight gain and leptin change in first-episode manic patients

    Institute of Scientific and Technical Information of China (English)

    金建烽; 严清章; 巢亚琴; 刘邦令; 丁睿鹰; 顾军

    2011-01-01

    目的:探讨丙戊酸钠、卡马西平对躁狂患者体质量及瘦素的影响.方法:80例未经药物治疗的首发躁狂患者,随机分为丙戊酸钠、卡马西平治疗组各40例.于治疗前,治疗2、4、6、8周,分别测定体重、瘦素.结果:(1)丙戊酸钠组体重、瘦素分别于治疗4,6周开始增高(均P<0.05);卡马西平组体重、瘦素则于治疗6周、8周开始增高(均P<0.05).(2)丙戊酸钠组治疗6周时的体重变化值,8周时的体重、瘦素变化值均高于卡马西平组(均P<0.05).(3)治疗8周时,丙戊酸钠组有55%的患者体重显著增加,高于卡马西平组的32.5%(P<0.05).(4)治疗6、8周时,丙戊酸钠组的体重、瘦素的变化值间有正相关(r=0.337、0.386,均P<0.05).结论:丙戊酸钠、卡马西平均可引起体重及瘦素的增高,但以丙戊酸钠更为显著.

  15. 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.

  16. 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.

  17. 高效液相色谱法测定血清中苯巴比妥、苯妥英、卡马西平、氯硝基安定的浓度%Determination of phenobarbital, phenytoin, carbamazepine and clonazepam in serum by HPLC

    Institute of Scientific and Technical Information of China (English)

    王增寿; 朱光辉; 李光乾

    2002-01-01

    目的:建立血清中苯巴比妥(PB)、苯妥英(PT)、卡马西平(CBZ)、氯硝基安定(CNZP)浓度测定的高效液相色谱法.方法:以PB、PT互为内标,ODS-Hypersil柱为分析柱,甲醇-水-β环糊精(45:55:0.01)为流动相;流速为0.8ml/min,紫外检测波长254nm.结果:PB、PT、CBZ、CNZP分离良好,最低检测浓度分别为0.25、0.5、0.05、0.015μg/ml;线性范围分别为2.5~40、2.5~40、1.25~20、0.02~0.32μg/ml;相对回收率分别为97.8%、102.1%、102.3%、103.3%;日内、日间RSD均小于10%.结论:该法操作简便,结果可靠,适用于临床开展药物浓度监测.

  18. The influence of Carbamazepine,Valproate and Topiramate on the cognitive function related to the frontal lobe among the newly diagnosed partial epilepsy%卡马西平、丙戊酸钠和托吡酯单药对新诊断部分癫痫患者额叶相关认知功能的影响

    Institute of Scientific and Technical Information of China (English)

    周波; 周东; 肖军; 孙红斌; 邹晓毅; 王强; 冯琼华

    2004-01-01

    目的研究卡马西平(CBZ)、丙戊酸钠(VAP)、托吡酯(TPM)对新诊断成人部分发作癫痫患者额叶相关认知功能的影响.方法采用前瞻和随机对照研究,对48例新诊断为部分发作伴或不伴全面发作的癫痫患者进行6项神经心理学测验后,随机给予CBZ、VAP、TPM单药治疗,1月后复查神经心理学检查.结果与治疗前比较CBZ组B型连线测验错误数增加(P<0.05),汉罗塔(Tower of Hanoi)平均计划时间缩短(P<0.05);VAP组Stroop读字正确数增加(P<0.01),威斯康星卡片分类测验(WSCT)错误数下降(P<0.05)、非持续错误数下降(P<0.01);TPM组倒背数下降(P<0.01).治疗后组间比较,有6项神经心理学指标差异有显著性,分别是顺背数(P<0.05)、词汇总数(P<0.01)、Stroop读字时间(P<0.01)、Stroop读字错误数(P<0.01)、Stroop读色纠正数(P<0.05)以及汉罗塔平均计划时间(P<0.01).结论抗癫痫药物的化学结构和作用机制不同,所以,对认知功能的影响也不同;TPM低剂量起始,缓慢加量,较低的治疗剂量可降低其对认知功能的影响.

  19. 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.

  20. 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.

  1. Ziprasidone Injection

    Science.gov (United States)

    ... called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain. ... following: antidepressants, carbamazepine (Carbatrol, Tegretol, Teril, others), certain antifungals such as ketoconazole (Extina, Nizoral), dopamine agonists such ...

  2. Mirtazapine

    Science.gov (United States)

    ... antidepressants. It works by increasing certain types of activity in the brain to maintain mental balance. ... Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); certain antifungals such as ketoconazole (Nizoral); buspirone; carbamazepine (Carbatrol, Epitol, ...

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

    OpenAIRE

    Kazmin, Aleksey; Wong, Renee C.; Sermer, Mathew; Koren, Gideon

    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)?

  4. New Drugs for Epilepsy: A Review

    OpenAIRE

    Verret, Simon

    1983-01-01

    Four relatively new drugs used as symptomatic treatment against epileptic seizures—carbamazepine (Tegretol), valproic acid (Depakene), clonazepam (Rivotril) and nitrazepam (Mogadon)—are reviewed from the standpoint of pharmacokinetic parameters, clinical indication, toxicity and practical use.

  5. 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.

  6. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro...

  7. Fate and Uptake of Pharmaceuticals in Soil–Plant Systems

    OpenAIRE

    Carter, Laura J.; Harris, Eleanor; Williams, Mike; Ryan, Jim J; Kookana, Rai S.; Boxall, Alistair B.A.

    2014-01-01

    Pharmaceuticals have been detected in the soil environment where there is the potential for uptake into crops. This study explored the fate and uptake of pharmaceuticals (carbamazepine, diclofenac, fluoxetine, propranolol, sulfamethazine) and a personal care product (triclosan) in soil–plant systems using radish (Raphanus sativus) and ryegrass (Lolium perenne). Five of the six chemicals were detected in plant tissue. Carbamazepine was taken up to the greatest extent in both the radish (52 μg/...

  8. Distribúcia štyroch humánnych farmaceutík, karbamazepínu, diklofenaku, gemfibrozilu a ibuprofénu v sústave sediment-voda

    OpenAIRE

    Krascsenits, Z.; Hiller, E.; Bartaľ, M.

    2008-01-01

    Laboratory studies were conducted to characterise the sorption-desorption behavior of four human pharmaceuticals (carbamazepine, diclofenac, gemfibrozil, and ibuprofen) at three initial concentrations in aqueous solution on one river sediment. The results of the experiments showed that distribution coefficients were either relatively low for diclofenac and ibuprofen or higher for gemfibrozil and carbamazepine. Distribution coefficients (mean Kd values for three initial concentrations), as mea...

  9. Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF

    OpenAIRE

    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.

    2015-01-01

    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 ...

  10. 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. PMID:26988391

  11. Effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice.

    Science.gov (United States)

    Grewal, Amarjot Kaur; Jaggi, Amteshwar Singh; Rana, Avtar Chand; Singh, Nirmal

    2013-12-01

    The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme (3α HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect. PMID:24381496

  12. Solubilization of active ingredients of different polarity in Pluronic® micellar solutions - Correlations between solubilizate polarity and solubilization site.

    Science.gov (United States)

    Nguyen-Kim, Viet; Prévost, Sylvain; Seidel, Karsten; Maier, Walter; Marguerre, Ann-Kathrin; Oetter, Günter; Tadros, Tharwat; Gradzielski, Michael

    2016-09-01

    The solubilization of two pharmaceutically active ingredients (AI) with significantly different water solubility, namely carbamazepine and fenofibrate (solubility of 150ppm and 10ppm, respectively), has been investigated using a series of Pluronics® (Poloxamers) containing different ethylene oxide and propylene oxide (EO/PO) units in the molecule. The results show largely enhanced solubilization of fenofibrate by Pluronic® micelles that increases with the PPO chain length provided the temperature is above the critical micelle temperature (cmt). In contrast the more water-soluble carbamazepine only shows a moderate increase in solubilization upon addition of Pluronics®. Small angle neutron scattering (SANS) and pulsed field gradient (PFG) NMR experiments show that the solubilization of fenofibrate occurs in the core of the micelles, whereas carbamazepine shows no direct association with the micelles. These clearly different solubilization mechanisms for the two AIs were confirmed by Nuclear Overhauser Enhancement Spectroscopy (NOESY) experiments, which show that fenofibrate interacts only with the PPO core of the micelle, whereas carbamazepine interacts with both PPO and PEO similarly. Accordingly, the large enhancement of the solubilization of fenofibrate is related to the fact that it is solubilized within the PPO core of the Pluronic® micelles, while the much more moderate increase of carbamazepine solubility is attributed to the change of solvent quality due to the presence of the amphiphilic copolymer and the interaction with the EO and PO units in solution. PMID:27244594

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

    Science.gov (United States)

    Chávez, Alma; Maya, Catalina; Gibson, Richard; Jiménez, Blanca

    2011-05-01

    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. PMID:21316131

  14. 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.

  15. Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network

    OpenAIRE

    Kaushik, Gaurav; Thomas, Michael A.; Aho, Ken A.

    2015-01-01

    Background Most cases of idiopathic autism spectrum disorder (ASD) likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a fetus to minute concentrations of pharmaceuticals, such as carbamazepine (CBZ), venlafaxine (VNX) and fluoxetine (FLX). Unmetabolized pharmaceuticals reach drinking water through a variety of routes, including ineffectively treated sewage. Previous studies in our laboratory examined the ex...

  16. 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.

  17. Antiepileptic Drugs with Mood Stabilizing Properties and Their Relation with Psychotropic Drug Use in Institutionalized Epilepsy Patients with Intellectual Disability

    Science.gov (United States)

    Leunissen, C. L. F.; de la Parra, N. M.; Tan, I. Y.; Rentmeester, Th. W.; Vader, C. I.; Veendrick-Meekes, M. J. B. M.; Aldenkamp, A. P.

    2011-01-01

    A large number of patients with epilepsy and intellectual disability take medication, amongst which antiepileptic and psychotropic drugs, often simultaneously. Certain antiepileptic drugs have mood-stabilizing properties, e.g. carbamazepine, valproic acid and lamotrigine. The aim of this study was to investigate whether the use of these…

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

    NARCIS (Netherlands)

    X. Qiao

    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

  19. Occipital seizures presenting with bilateral visual loss

    OpenAIRE

    Hadjikoutis S; Sawhney I

    2003-01-01

    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.

  20. 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. PMID:21145232

  1. Eslicarbazepine acetate in the management of refractory bipolar disorder.

    Science.gov (United States)

    Nath, Kamal; Bhattacharya, Arnab; Praharaj, Samir Kumar

    2012-01-01

    Eslicarbazepine acetate is a novel third-generation antiepileptic related to carbamazepine and oxcarbazepine with a benign adverse effect profile. We report a patient with bipolar mania with intolerance to multiple antimanic drugs, responding to eslicarbazepine without any serious adverse effect. PMID:23151469

  2. 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

    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, with...

  3. Pharmaceutical residues in aquatic systems: mode of action and effects on mussel physiology

    OpenAIRE

    Buratti, Sara

    2011-01-01

    Pharmaceutical residues contaminate aquatic ecosystems as a result of their widespread human and veterinary usage. Since continuously released and not efficiently removed, certain pharmaceuticals exhibit pseudo-persistence thus generating concerns for the health of aquatic wildlife. This work aimed at assessing on mussels Mytilus galloprovincialis, under laboratory conditions, the effects of three pharmaceuticals, carbamazepine (antiepileptic), propranolol (β-blocker) and oxytetracycline (...

  4. Drug hypersensitivity syndrome

    OpenAIRE

    Rashmi Kumari; Dependra K Timshina; Devinder Mohan Thappa

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalit...

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

    International Nuclear Information System (INIS)

    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.

  6. Bone mineral density in adult patients treated with various antiepileptic drugs

    DEFF Research Database (Denmark)

    Beniczky, Simona Alexandra; Viken, Janina; Jensen, Lars Thorbjørn;

    2012-01-01

    adult consecutive outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared the incidence of decreased BMD among the patients treated with 6 different AEDs: carbamazepine (CBZ), oxcarbazepine (OXC), valproic acid (VPA), lamotrigine (LTG), topiramate (TPM...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. [Future direction of pharmacogenomics: identification of genes associated with risk of adverse drug reactions using genome-wide association study].

    Science.gov (United States)

    Mushiroda, Taisei

    2014-01-01

    Drug-induced skin rash characterized by an acute inflammatory reaction of skin and mucous membranes is dose-independent, unpredictable, and sometimes life-threatening. In recent years, the U.S. Food and Drug Administration (FDA) has recommended genotyping of polymorphisms in the human leukocyte antigen (HLA) prior to drug administration for the avoidance of severe skin rash induced by drugs, such as abacavir and carbamazepine. A genome-wide association study (GWAS) is useful for the identification of genomic biomarkers that can predict the efficacy or risk of toxicity of various drugs. We identified novel susceptibility loci associated with the risk of a skin rash induced by nevirapine and carbamazepine in Thai and Japanese populations, respectively, through case-control GWAS with high-throughput single-nucleotide polymorphism (SNP) genotyping technology. In order to apply the genomic biomarkers to clinical therapeutics, prospective clinical trials will be necessary for the evaluation of an intervention based on genetic tests. PMID:24724431

  14. Does Uptake of Pharmaceuticals Vary Across Earthworm Species?

    Science.gov (United States)

    Carter, Laura J; Ryan, Jim J; Boxall, Alistair B A

    2016-09-01

    This study compared the uptake and depuration of four commonly used pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in two earthworm species (Lumbricus terrestris and Eisenia fetida). L. terrestris are a larger species and often found in deep burrows whereas E. fetida prefer to reside near the soil surface. Species burrowing habits and sizes may alter uptake by earthworms. All four pharmaceuticals were taken up into both L. terrestris and E. fetida tissue after 21 days exposure to spiked soil. Bioconcentration factors (BCFs) ranged between 1.72 and 29.83 for L. terrestris and 1.14 and 63.03 for E. fetida. For carbamazepine and diclofenac, BCFs were similar whereas for fluoxetine and orlistat, BCFs in E. fetida were more than double those seen in L. terrestris. Results indicate that uptake into earthworms cannot be generalised between species and that the influence of species traits can vary depending on the nature of the study chemical. PMID:27443341

  15. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie;

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  16. 8-hydroxy-dipropylaminotetralin promotes neural plasticity in epileptic rats with depression

    Institute of Scientific and Technical Information of China (English)

    Ping Yang; Meizhen Sun; Liang Li; Yihua Shen

    2012-01-01

    Rats with chronic pilocarpine-induced temporal lobe epilepsy complicated with depression were studied. Anti-5-bromodeoxyuridine immunofluorescence staining and Timms staining showed that neurogenesis within the hippocampal dentate gyrus and mossy fiber sprouting were increased in model rats. Neurogenesis within the hippocampal dentate gyrus was further enhanced, while mossy fiber sprouting was decreased in model rats administered carbamazepine alone or in combination with the 5-hydroxytryptamine 1A receptor agonist, 8-hydroxy-dipropylaminotetralin (0.1 and 1 mg/kg). Among the groups, the effect was the most significant in rats receiving carbamazepine in conjunction with 1 mg/kg 8-hydroxy-dipropylaminotetralin. Thus, high dose 8-hydroxy-dipropylaminotetralin can improve neural plasticity in epileptic rats with depression.

  17. EFFECT OF SEIZURE CONTROL ON IMPROVEMENT OF COGNITIVE FUNCTIONS IN EPILEPTIC PATIENTS

    OpenAIRE

    Nainian, M.R.; Behere, P.B.; Mohanti, S.

    1993-01-01

    SUMMARY A group of fifty epileptic patients were tested with neuropsychological tools for cognitive functions like memory, intelligence, visuomotor coordination, spatial perception and body schema perception. Patients were on carbamazepine and were tested after three months. Seizure improvement was shown to have different effects on different cognitive functions. Memory and intellectual deficits improved, while no difference was observed in visuomotor coordination, spatial and personal percep...

  18. Effect of N-(m-bromoanilinomethyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

    OpenAIRE

    Luszczki Jarogniew J.; Marzeda Ewa; Kondrat-Wrobel Maria W.; Pyrka Daniel; Kocharov Sergey L.; Florek-Luszczki Magdalena

    2014-01-01

    The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl)- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock (MES)-induced tonic seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 ...

  19. Exposure of the Main Italian River Basin to Pharmaceuticals

    OpenAIRE

    Federico Ferrari; Agata Gallipoli; Matteo Balderacchi; Maria M. Ulaszewska; Ettore Capri; Marco Trevisan

    2011-01-01

    This study give a preliminary survey of pharmaceutical contamination and accumulation in surface waters and sediments along the river Po basin (74,000 km2, the largest in Italy), a strategic region for the Italian economy: it collects sewage from a vast industrialized area of Italy (Autorità di Baciono del fiume Po, 2006, 2009). 10 pharmaceuticals (atenolol, propanolol, metoprolol, nimesulide, furosemide, carbamazepine, ranitidine, metronidazole, paracetamol, and atorvastatin) from several th...

  20. Gene-class analysis of expression patterns induced by psychoactive pharmaceutical exposure in fathead minnow (Pimephales promelas) indicates induction of neuronal systems☆

    OpenAIRE

    Thomas, Michael A.; Joshi, Parag P.; Klaper, Rebecca D.

    2011-01-01

    Psychoactive pharmaceuticals are among the most frequently prescribed drugs, contributing to persistent measurable concentrations in aquatic systems. Typically, it is assumed that such contaminants have no human health implications because they exist in extremely low concentrations. We exposed juvenile fathead minnows (Pimephales promelas) to three pharmaceuticals, fluoxetine, venlafaxine and carbamazepine, individually and in a mixture, and measured their effect on the induction of gene expr...

  1. Effects of Mixture of Pharmaceuticals on Early Life Stages of Tench (Tinca tinca)

    OpenAIRE

    Vlasta Stancova; Lucie Plhalova; Marta Bartoskova; Dana Zivna; Miroslav Prokes; Petr Marsalek; Jana Blahova; Misa Skoric; Zdenka Svobodova

    2014-01-01

    Ubiquitous occurrence of pharmaceuticals in aquatic environment results in concern about potential adverse the effects on nontarget organisms. In water, drugs are present in complex mixtures, in which complicated interactions affect toxicity of single components. The purpose of this study was to examine effect of 35-day-long exposure to mixture of ibuprofen, diclofenac, and carbamazepine on the mortality, growth, early ontogeny, and histopathological changes in tench (Tinca tinca). Early life...

  2. Effects of soil properties on the uptake of pharmaceuticals into earthworms

    OpenAIRE

    Carter, Laura Jayne; Ryan, Jim J; Boxall, Alistair Bruce Alleyne

    2016-01-01

    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 Ei...

  3. Levels of pharmaceuticals in Slovene municipal and hospital wastewaters: a preliminary study

    OpenAIRE

    Klančar, Anita; Trontelj, Jurij; Kristl, Albin; Zupančič Justin, Maja; Roškar, Robert

    2016-01-01

    Pharmaceuticals in wastewater have clearly raised concern and a broad range of analytical methods has been used to assess the risk as accurately as possible. The aim of our study was to measure and compare the concentrations of atorvastatin, bisoprolol, carbamazepine, ciprofloxacin, clofibric acid, diclofenac, fluoxetine, metoprolol, and sertraline in wastewater samples taken from one municipal and one hospital wastewater treatment plant in Slovenia and to predict the potential environmental ...

  4. Occurrence of pharmaceuticals in municipal wastewater treatment plants and receiving surface waters in Central and Southern Finland

    OpenAIRE

    Lindholm-Lehto, Petra

    2016-01-01

    The presence of five selected pharmaceuticals, four anti-inflammatory drugs, diclofenac, ibuprofen, ketoprofen, naproxen, and an antiepileptic drug carbamazepine, was determined at four municipal wastewater treatment plants (WWTPs) and in the receiving waterway near the city of Jyväskylä, in central Finland and also in the River Vantaa. First, an analytical method was developed including a pretreatment and purification followed by liquid chromatography coupled to tandem mass spectrometry (LC-...

  5. POCIS passive samplers as a monitoring tool for pharmaceutical residues and their transformation products in marine environment

    OpenAIRE

    Bueno, M. J. M.; Herrera, S.; Munaron, D.; Boillot, C.; Fenet, H.; Chiron, Serge; Gomez, E

    2016-01-01

    In the last years, several scientific studies have shown that carbamazepine (CBZ) is one of the most frequently detected pharmaceutical in aquatic environment. However, little data is available on its detection and its transformation products (TPs) in marine water. The use of polar organic chemical integrative sampling (POCIS) passive samplers as a semi-quantitative and qualitative tool for screening of pharmaceuticals and TPs in seawater has been studied. Furthermore, the uptake rates of the...

  6. Does Uptake of Pharmaceuticals Vary Across Earthworm Species?

    OpenAIRE

    Carter, Laura Jayne; Ryan, Jim J; Boxall, Alistair Bruce Alleyne

    2016-01-01

    This study compared the uptake and depuration of four commonly used pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in two earthworm species (Lumbricus terrestris and Eisenia fetida). L. terrestris are a larger species and often found in deep burrows whereas E. fetida prefer to reside near the soil surface. Species burrowing habits and sizes may alter uptake by earthworms. All four pharmaceuticals were taken up into both L. terrestris and E. fetida tissue after 21 days ex...

  7. Successful use of stellate ganglion block and a new centrally acting analgesic with dual mode of action in a resistant temporomandibular joint pain

    OpenAIRE

    Jones, Gareth Peter; Tripathi, Shiva Shankar

    2014-01-01

    Stellate ganglion blocks have been shown to provide effective pain relief in a number of different conditions involving the upper body. This was demonstrated in a 65-year-old woman who had experienced severe debilitating pain in her left temporomandibular joint (TMJ) and the surrounding area of her face for over 10 years. The pain was unresponsive to indomethacin, carbamazepine, sodium valproate, gabapentin, lithium, melatonin and amitriptyline. She had also had four surgical procedures to th...

  8. The impact on receiving waters of pharmaceutical residues and antibiotic resistant faecal bacteria found in urban waste water effluents

    OpenAIRE

    Tuckwell, Rebecca

    2015-01-01

    Pharmaceuticals intended for human use are frequently detected in the aquatic environment. This is predominantly from their excretion following ingestion and subsequent discharge in domestic sewage. Wastewater treatment provides an opportunity to control their release to surface waters however, their removal is often incomplete. This thesis addresses this pharmaceutical pathway and the potential impact on the aquatic environment. The progress of bezafibrate, carbamazepine, ciprofloxacin a...

  9. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity

    OpenAIRE

    Pirmohamed, Munir; Ostrov, David A.; Park, B. Kevin

    2015-01-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different...

  10. Effects of chronic treatment with commonly used antiepileptic drugs on passive avoidance learning in prepubertal rats

    OpenAIRE

    Yildirim, Mehmet; ABİDİN, Ismail; CANSU, Ali

    2013-01-01

    Antiepileptic drugs (AEDs), which are widely used to control and prevent epileptic seizures in children with epilepsy, have potential cognitive side effects. There have been several reports respecting different effects of the first and second generation ADEs on learning and memory. Therefore, we investigated the effects of valproate, carbamazepine, levetiracetam, oxcarbazepine, lamotrigine and topiramate, administered chronically by gavage for 21 days, on learning and memory retention of male...

  11. Elimination of Micropollutants using Engineered Constructed Wetlands – A Laboratory Scale Study

    OpenAIRE

    Rossi, Luca; Brovelli, Alessandro; Queloz, Pierre; Ho, Dien; Barry, David Andrew

    2011-01-01

    In Switzerland, a new standard for wastewater treatment plants (WWTP) – 80% reduction of micropollutants from raw sewage – is under consideration. Five substances have been proposed as target compounds: Diclofenac, Carbamazepine, Mecoprop, Sulfamethoxazole and Benzotriazole. Although very efficient and reliable, advanced treatment technologies for traditional WWTPs – such as ozonation – are expensive and difficult to implement on relatively small WWTPs, of which there are many in Switzerland....

  12. Etude de l'impact de micropolluants pharmaceutiques sur le colmatage des BAM utilisés en traitement des eaux usées urbaines : cas de la carbamazépine

    OpenAIRE

    Li, Chengcheng

    2014-01-01

    Membrane fouling still remains the main limitation for the development of membrane bioreactor (MBR). In this thesis, the main objective focuses on the effects of pharmaceutical micropollutants which are frequently found in domestic wastewater on MBR fouling. Carbamazepine (CBZ), an anti-epileptic drug, was chosen in this study due to its occurrence in domestic wastewater and persistency in MBR process. The effects of CBZ on MBR fouling were investigated in two different ways of contact, i.e. ...

  13. Suspected-target screening strategy to investigate degradation by ozonation or photolysis of urban micropollutants in waste waters

    OpenAIRE

    Bados, P.; Mathon, B.; Brzokewicz, T.; Choubert, J.M.; Chovelon, J.M.; Coquery, M.; Miege, C.

    2015-01-01

    Conventional wastewater treatment plants (WWTPs) partially eliminate micropollutants present in domestic and industrial discharges (Martin-Ruel et al., 2010; Choubert et al., 2011). However, some molecules still occur in effluents of WWTPs at concentrations close to 0.1 μg/L for some pesticides (e.g. diuron) and pharmaceuticals (e.g., carbamazepine, sotalol, diclofenac). The potential hazard of these compounds requires the development of new processes (tertiary) to anticipate possible re...

  14. A Review of Eslicarbazepine Acetate for the Adjunctive Treatment of Partial-Onset Epilepsy

    OpenAIRE

    Singh, Rajinder P.; Asconapé, Jorge J.

    2011-01-01

    Eslicarbazepine acetate (ESL) is a novel antiepileptic drug indicated for the treatment of partial-onset seizures. Structurally, it belongs to the dibenzazepine family and is closely related to carbamazepine and oxcarbazepine. Its main mechanism of action is by blocking the voltage-gated sodium channel. ESL is a pro-drug that is rapidly metabolized almost exclusively into S-licarbazepine, the biologically active drug. It has a favorable pharmacokinetic and drug-drug interaction profile. Howev...

  15. Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

    OpenAIRE

    Morte, Maria I.; Carreira, Bruno P.; Falcão, Maria J.; Ambrosio, António M.; Soares-da-Silva, Patrício; Araújo, Inês M.; Carvalho, Caetana M.

    2013-01-01

    In this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic p...

  16. Update on the role of eslicarbazepine acetate in the treatment of partial-onset epilepsy

    OpenAIRE

    Tambucci R; Basti C; Maresca M.; Coppola G.; Verrotti A

    2016-01-01

    Renato Tambucci,1 Claudia Basti,1 Maria Maresca,1 Giangennaro Coppola,2 Alberto Verrotti11Department of Pediatrics, University of L’Aquila, L’Aquila, Italy; 2Child and Adolescent Neuropsychiatry Unit, University of Salerno, Salerno, ItalyAbstract: Eslicarbazepine acetate (ESL) is a once daily new third generation antiepileptic drug that shares the basic chemical structure of carbamazepine and oxcarbazepine – a dibenzazepine nucleus with the 5-ca...

  17. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients

    DEFF Research Database (Denmark)

    Weckhuysen, S.; Ivanovic, V.; Hendrickx, R.;

    2013-01-01

    . Recurrent mutations lead to relatively homogenous phenotypes. One patient responded favorably to retigabine; 5 patients had a good response to carbamazepine. In 6 patients, seizures with bradycardia were recorded. One patient died of probable sudden unexpected death in epilepsy. CONCLUSION: KCNQ2 mutations...... cause approximately 13% of unexplained NEE. Patients present with a wide spectrum of severity and, although rare, infantile epilepsy onset is possible....

  18. Recurrent pain of a pseudotabetic variety after laminectomy for lumbar disc lesion.

    OpenAIRE

    Martin, G.

    1980-01-01

    A variety of pain resembling the lightning pains of tabes dorsalis is described in patients suffering from persistent sciatica, following laminectomy for lumbar disc disease. It occurs in about 13% of those complaining of post-laminectomy pain and in 5% of all those having a laminectomy for disc disease. It is associated with damage to the nerve root and may be precipitated by nerve root resection. About half the patients may get some relief from carbamazepine or clonazepam and the syndrome s...

  19. Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice

    OpenAIRE

    Kartik N. Shah; Rana, Devang A.; Patel, Varsha J.

    2014-01-01

    Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetra...

  20. 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

    2009-08-01

    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. PMID:19657534

  1. 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.

  2. The place of peripheral neurectomy in the management of trigeminal neuralgia.

    OpenAIRE

    Freemont, A. J.; Millac, P

    1981-01-01

    One hundred and forty-six patients with trigeminal neuralgia were studied. Of 49 patients ultimately maintained pain-free by non-medical means, 26 underwent peripheral neurectomy. Twenty of these achieved excellent pain control in the longer term and 5 of the remaining 6 became more responsive to carbamazepine after operation. Seven patients required repeat neurectomies. Peripheral neurectomy is a useful and simple method of pain control in trigeminal neuralgia.

  3. Determination of anti-anxiety and anti-epileptic drugs in hospital effluent and a preliminary risk assessment.

    Science.gov (United States)

    de Almeida, Carlos Alberto A; Brenner, Carla G B; Minetto, Luciane; Mallmann, Carlos A; Martins, Ayrton F

    2013-11-01

    In this study, an analytical methodology was developed for the determination of psycho-active drugs in the treated effluent of the University Hospital at the Federal University of Santa Maria, RS - Brazil. Samples were collected from point A (Emergency) and point B (General effluent). The adopted methodology included a pre-concentration procedure involving the use of solid phase extraction and determination by liquid chromatography coupled to mass spectrometry. The limit of detection for bromazepam and lorazepam was 4.9 ± 1.0 ng L(-1) and, for carbamazepine, clonazepam and diazepam was 6.1 ± 1.5 ng L(-1). The limit of quantification was 30.0 ± 1.1 ng L(-1), for bromazepam, clonazepam and lorazepam; for carbamazepine was 50.0 ± 1.8 ng L(-1) and was 40.0 ± 1.0 ng L(-1) for diazepam. The mean concentrations in the Emergency and General effluent treated currents were as follows: for bromazepam, 195 ± 6 ng L(-1) and 137 ± 7 ng L(-1); for carbamazepine, 590 ± 6 ng L(-1) and 461 ± 10 ng L(-1); for diazepam, 645 ± 1 ng L(-1) and 571 ± 10 ng L(-1); for lorazepam, 96 ± 7 ng L(-1) and 42 ± 4 ng L(-1); and for clonazepam, 134 ± 10 ng L(-1) and 57 ± 10 ng L(-1). A preliminary risk assessment was conducted: carbamazepine and diazepam require considerable attention owing to their environmental toxicity. The occurrence of these psychoactive-drugs and the environmental risks that they pose demonstrated the need for a more efficient treatment system. As far we are aware, there have been no comparable studies to this on the hazards of hospital effluents in Brazil, and very few that have carried out a risk assessment of psycho-active drugs in hospital effluent in general. PMID:24034828

  4. Ozone oxidation of antidepressants in wastewater –Treatment evaluation and characterization of new by-products by LC-QToFMS

    OpenAIRE

    Lajeunesse André; Blais Mireille; Barbeau Benoît; Sauvé Sébastien; Gagnon Christian

    2013-01-01

    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 investigat...

  5. Some ozone advanced oxidation processes to improve the biological removal of selected pharmaceutical contaminants from urban wastewater

    OpenAIRE

    Espejo, Azahara; Aguinaco, Almudena; Amat Payá, Ana María; Fernando J. Beltrán

    2014-01-01

    Removal of nine pharmaceutical compounds¿acetaminophen (AAF), antipyrine (ANT), caffeine (CAF), carbamazepine (CRB), diclofenac (DCF), hydrochlorothiazide (HCT), ketorolac (KET), metoprolol (MET) and sulfamethoxazole (SMX)¿spiked in a primary sedimentation effluent of a municipal wastewater has been studied with sequential aerobic biological and ozone advanced oxidation systems. Combinations of ozone, UVA black light and Fe(III) or Fe3O4 constituted the chemical systems. During the ...

  6. The concentration of three anti-seizure medications in hair: the effects of hair color, controlling for dose and age

    OpenAIRE

    2001-01-01

    Background This paper assess the relationship between the quantity of three anti-seizure medications in hair and the color of the analyzed hair, while controlling for the effects of dose, dose duration, and patient age for 140 clinical patients undergoing anti-seizure therapy. Three drugs are assessed: carbamazepine (40 patients), valproic acid (40 patients), and phenytoin (60 patients). The relationship between hair assay results, hair color, dose, dose duration, and age is modeled using an ...

  7. 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.

  8. 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.

  9. Effect of Neurosteroid Modulation on Global Ischaemia-Reperfusion-Induced Cerebral Injury in Mice

    OpenAIRE

    Grewal, Amarjot Kaur; Jaggi, Amteshwar Singh; Rana, Avtar Chand; Singh, Nirmal

    2013-01-01

    The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved ...

  10. Effect of the Dysbindin Gene on Antimanic Agents in Patients with Bipolar I Disorder

    OpenAIRE

    Yun, Dong-Hwan; Pae, Chi-Un; Drago, Antonio; Mandelli, Laura; De Ronchi, Diana; Patkar, Ashwin A.; Paik, In Ho; Serretti, Alessandro; Kim, Jung-Jin

    2008-01-01

    Objective We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. Methods A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (±19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) ...

  11. Antiepileptic Drugs in the Treatment of Anxiety Disorders

    OpenAIRE

    Levent Mete; Sinem Akyalcin; Pinar Cetinay Aydin

    2009-01-01

    In addition to epilepsy, antiepileptic drugs are used in neurologic conditions such as chronic pain and in the treatment of bipolar disorder in psychiatry. There are studies reporting its use in the treatment of anxiety disorders. The efficacy of antiepileptic drugs as carbamazepine, valproic asid, lamotrigine, topiramate, gabapentin, pregabalin in anxiety disorders has been shown in some clinical studies. The strongest evidence has been presented for pregabalin in generalized anxiety disorde...

  12. Treating bipolar disorder. Evidence-based guidelines for family medicine.

    OpenAIRE

    McIntyre, Roger S; Mancini, Deborah A.; Lin, Peter; Jordan, John

    2004-01-01

    OBJECTIVE: To provide an evidence-based summary of medications commonly used for bipolar disorders and a practical approach to managing bipolar disorders in the office. QUALITY OF EVIDENCE: Articles from 1990 to 2003 were selected from MEDLINE using the key words "bipolar disorder," "antiepileptics," "antipsychotics," "antidepressants," and "mood stabilizers." Good-quality evidence for many of these treatments comes from randomized trials. Lithium, divalproex, carbamazepine, lamotrigine, oxca...

  13. 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.

  14. 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.

  15. Metabolism of pharmaceutical and personal care products by carrot cell cultures.

    Science.gov (United States)

    Wu, Xiaoqin; Fu, Qiuguo; Gan, Jay

    2016-04-01

    With the increasing use of treated wastewater and biosolids in agriculture, residues of pharmaceutical and personal care products (PPCPs) in these reused resources may contaminate food produce via plant uptake, constituting a route for human exposure. Although various PPCPs have been reported to be taken up by plants in laboratories or under field conditions, at present little information is available on their metabolism in plants. In this study, we applied carrot cell cultures to investigate the plant metabolism of PPCPs. Five phase I metabolites of carbamazepine were identified and the potential metabolism pathways of carbamazepine were proposed. We also used the carrot cell cultures as a rapid screening tool to initially assess the metabolism potentials of 18 PPCPs. Eleven PPCPs, including acetaminophen, caffeine, meprobamate, primidone, atenolol, trimethoprim, DEET, carbamazepine, dilantin, diazepam, and triclocarban, were found to be recalcitrant to metabolism. The other 7 PPCPs, including triclosan, naproxen, diclofenac, ibuprofen, gemfibrozil, sulfamethoxazole, and atorvastatin, displayed rapid metabolism, with 0.4-47.3% remaining in the culture at the end of the experiment. Further investigation using glycosidase hydrolysis showed that 1.3-20.6% of initially spiked naproxen, diclofenac, ibuprofen, and gemfibrozil were transformed into glycoside conjugates. Results from this study showed that plant cell cultures may be a useful tool for initially exploring the potential metabolites of PPCPs in plants as well as for rapidly screening the metabolism potentials of a variety of PPCPs or other emerging contaminants, and therefore may be used for prioritizing compounds for further comprehensive evaluations. PMID:26745399

  16. Investigating the removal of some pharmaceutical compounds in hospital wastewater treatment plants operating in Saudi Arabia.

    Science.gov (United States)

    Al Qarni, Hamed; Collier, Philip; O'Keeffe, Juliette; Akunna, Joseph

    2016-07-01

    The concentrations of 12 pharmaceutical compounds (atenolol, erythromycin, cyclophosphamide, paracetamol, bezafibrate, carbamazepine, ciprofloxacin, caffeine, clarithromycin, lidocaine, sulfamethoxazole and N-acetylsulfamethoxazol (NACS)) were investigated in the influents and effluents of two hospital wastewater treatment plants (HWWTPs) in Saudi Arabia. The majority of the target analytes were detected in the influent samples apart from bezafibrate, cyclophosphamide, and erythromycin. Caffeine and paracetamol were detected in the influent at particularly high concentrations up to 75 and 12 ug/L, respectively. High removal efficiencies of the pharmaceutical compounds were observed in both HWWTPs, with greater than 90 % removal on average. Paracetamol, sulfamethoxazole, NACS, ciprofloxacin, and caffeine were eliminated by between >95 and >99 % on average. Atenolol, carbamazepine, and clarithromycin were eliminated by >86 % on average. Of particular interest were the high removal efficiencies of carbamazepine and antibiotics that were achieved by the HWWTPs; these compounds have been reported to be relatively recalcitrant to biological treatment and are generally only partially removed. Elevated temperatures and high levels of sunlight were considered to be the main factors that enhanced the removal of these compounds. PMID:26996911

  17. Role of wetland organic matters as photosensitizer for degradation of micropollutants and metabolites.

    Science.gov (United States)

    Lee, Eunkyung; Shon, Ho Kyong; Cho, Jaeweon

    2014-07-15

    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 (3)DOM(*)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 ((3)DOM(*)) 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 by the interaction with (3)DOM(*) in wetlands. PMID:24862465

  18. Pharmaceutical load in sewage sludge and biochar produced by hydrothermal carbonization.

    Science.gov (United States)

    vom Eyser, C; Palmu, K; Schmidt, T C; Tuerk, J

    2015-12-15

    We investigated the removal of twelve pharmaceuticals in sewage sludge by hydrothermal carbonization (HTC), which has emerged as a technology for improving the quality of organic waste materials producing a valuable biochar material. In this study, the HTC converted sewage sludge samples to a biochar product within 4h at a temperature of 210 °C and a resulting pressure of about 15 bar. Initial pharmaceutical load of the sewage sludge was investigated as well as the residual concentrations in biochar produced from spiked and eight native sewage sludge samples from three waste water treatment plants. Additionally, the solid contents of source material and product were compared, which showed a considerable increase of the solid content after filtration by HTC. All pharmaceuticals except sulfamethoxazole, which remained below the limit of quantification, frequently occurred in the investigated sewage sludges in the μg/kg dry matter (DM) range. Diclofenac, carbamazepine, metoprolol and propranolol were detected in all sludge samples with a maximum concentration of 800 μg/kgDM for metoprolol. HTC was investigated regarding its contaminant removal efficiency using spiked sewage sludge. Pharmaceutical concentrations were reduced for seven compounds by 39% (metoprolol) to≥97% (carbamazepine). In native biochar samples the four compounds phenazone, carbamazepine, metoprolol and propranolol were detected, which confirmed that the HTC process can reduce the load of micropollutants. In contrast to the other investigated compounds phenazone concentration increased, which was further addressed in thermal behaviour studies including three structurally similar potential precursors. PMID:26282751

  19. The impact of interacting drugs on dispensed doses of warfarin in the Swedish population: A novel use of population based drug registers.

    Science.gov (United States)

    Andersson, M L; Lindh, J D; Mannheimer, B

    2013-12-01

    To investigate the impact of interacting drugs on the dispensed doses of warfarin in the Swedish population. This was a retrospective, cross-sectional population based register study of patients being dispensed warfarin. Warfarin doses were estimated in different age groups, in men and women, and in patients using interacting drugs. The influence of interacting drugs on the dispensed warfarin dose was analyzed using multiple regression. All 143,729 patients dispensed warfarin were analyzed. The dispensed dose of warfarin was highest in patients 30-39 years old and decreased with age. Co-medication with carbamazepine, simvastatin, paracetamol, amiodarone, fluconazole, lactulose, or bezafibrate was associated with significant changes in dispensed warfarin doses, by +40%, -3.4%, -7.3%, -8.2%, -8.8%, -9.0%, and -9.7%, respectively. After adjustment for age and gender, sulfamethoxazole was also found to significantly alter the dispensed warfarin dose (-6.1%). We provide new support for the previous scarce evidence of interactions between warfarin and carbamazepine, bezafibrate, and lactulose. Initiation or discontinuation of bezafibrate or lactulose in a patient on warfarin should warrant close clinical monitoring. The marked increased warfarin requirement associated with carbamazepine use supports moving from a more conservative reactive towards a proactive strategy including preventive warfarin dose adjustments to avoid potential adverse effects. PMID:24038065

  20. 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.

  1. Determination of pharmaceuticals in groundwater collected in five cemeteries' areas (Portugal).

    Science.gov (United States)

    Paíga, P; Delerue-Matos, C

    2016-11-01

    There are growing public attention and concern about the possibility of ecosystem and human health effects from pharmaceuticals in environment. Several types of environmental samples were target of studies by the scientific community, namely drinking water, groundwater, surface water (river, ocean), treated water (influent and effluent), soils, and sediments near to Wastewater Treatment Plants or near to others potential sources of contaminations. Normally, studies in the cemeteries areas are for historical and architectural research and questions of the potential risk for adverse impact of cemeteries in environment have never received enough attention. However, this risk may exist when cemeteries are placed in areas that are vulnerable to contamination. The objective of the present work was the determination of pharmaceuticals (nonsteroidal anti-inflammatory/analgesics, antibiotics and psychiatric drugs) in groundwater samples collected inside of the cemeteries areas. Acetaminophen, salicylic acid, ibuprofen, ketoprofen, nimesulide, carbamazepine, fluoxetine, and sertraline were the pharmaceuticals achieved in the analysed samples. None of the studied antibiotics were detected. The highest concentration was obtained for salicylic acid (in the range of 33.7 to 71.0ng/L) and carbamazepine (between 20.0 and 22.3ng/L), respectively. By the cluster analysis similarity between carbamazepine and fluoxetine was achieved. PMID:27328395

  2. 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. PMID:26738990

  3. 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.

  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. PMID:27393211

  5. 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

  6. 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.

  7. 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

  8. Evaluation of memory enhancing clinically available standardized extract of Bacopa monniera on P-glycoprotein and cytochrome P450 3A in Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Rajbir Singh

    Full Text Available Bacopa monniera is a traditional Ayurvedic herbal medicine used to treat various mental ailments from ancient times. Recently, chemically standardized alcoholic extract of Bacopa monniera (BM has been developed and currently available as over the counter herbal remedy for memory enhancement in children and adults. However, the consumption of herbal drugs has been reported to alter the expression of drug metabolizing enzymes and membrane transporters. Present study in male Sprague-Dawley rat was performed to evaluate the effect of memory enhancing standardized extract of BM on hepatic and intestinal cytochrome P450 3A and P-glycoprotein expression and activity. The BM (31 mg/kg/day was orally administered for one week in BM pre-treated group while the control group received the same amount of vehicle for the same time period. The BM treatment decreased the cytochrome P450 3A (CYP3A mediated testosterone 6β-hydroxylation activity of the liver and intestine by 2 and 1.5 fold, respectively compared to vehicle treated control. Similarly pretreatment with BM extract decreased the expression of intestinal P-glycoprotein (Pgp as confirmed by Western blot analysis but did not alter the expression of hepatic Pgp. To investigate whether this BM pretreatment mediated decrease in activity of CYP3A and Pgp would account for the alteration of respective substrate or not, pharmacokinetic study with carbamazepine and digoxin was performed in BM pre-treated rats and vehicle treated rats. Carbamazepine and digoxin were used as CYP3A and Pgp probe drugs, respectively. Significant increase in AUC and Cmax of carbamazepine (4 and 1.8 fold and digoxin (1.3 and 1.2 fold, respectively following the BM pre-treatment confirmed the down regulation of CYP3A and Pgp.

  9. Photo-regenerable multi-walled carbon nanotube membranes for the removal of pharmaceutical micropollutants from water.

    Science.gov (United States)

    Zaib, Qammer; Mansoor, Bilal; Ahmad, Farrukh

    2013-08-01

    Pharmaceutical micropollutants fall in the category of "emerging contaminants" in water because of their prevalence and persistence in the aqueous environment, and because of a poor understanding of their low-dose exposure effects on human and animal populations. In this study, photo-regenerable multiwalled carbon nanotube membranes with variable water permeabilities were produced by embedding hierarchical TiO2 structures (having porous, spherical morphology) onto a pre-deposited bed of multi-walled carbon nanotubes (MWNTs) using a modified sol-gel technique. These MWNT-TiO2 composites and their constituent materials were characterized by analytical electron microscopy, surface charge measurement, thermogravimetric analysis, and hydrophobicity determination. The adsorption removal potential of MWNT-TiO2 membranes was demonstrated for three representative pharmaceuticals: acetaminophen, carbamazepine and ibuprofen. The peak initial removal percentages of the pharmaceuticals by the MWNT-TiO2 membranes were 80%, 45%, and 24% for carbamazepine, ibuprofen, and acetaminophen, respectively. The ability of the membranes to be regenerated, once they were saturated with the pharmaceutical compounds, was verified by repeating the adsorption removal experiment on the same membranes after exposure to UV light at 254 nm. Peak removal efficiencies after regeneration were 55%, 32%, and 19% for carbamazepine, ibuprofen, and acetaminophen, respectively, indicating some loss in sorptive capacity upon regeneration. Furthermore, the effect of pH on adsorption of ibuprofen, the pharmaceutical that attained the highest mass loading on the sorbent at equilibrium saturation, was studied and its mechanism of adsorption was proposed at pH below pKa. PMID:23811952

  10. Pharmacokinetic interactions of the macrolide antibiotics.

    Science.gov (United States)

    Ludden, T M

    1985-01-01

    The macrolide antibiotics erythromycin and triacetyloleandomycin (troleandomycin) are prescribed for many types of infections. As such they are often added to other preexisting drug therapy. Thus, there are frequent opportunities for the interaction of these antibiotics with other drugs. Both erythromycin and triacetyloleandomycin appear to have the potential to inhibit drug metabolism in the liver and also drug metabolism by micro-organisms in the gut, either through their antibiotic effect or through complex formation and inactivation of microsomal drug oxidising enzymes. Of the two agents, triacetyloleandomycin appears to be the more potent inhibitor of microsomal drug metabolism. Published studies indicate that triacetyloleandomycin can significantly decrease the metabolism of methylprednisolone, theophylline and carbamazepine. Its ability to cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in patients on oral contraceptives may also be related to its inhibitory effect on drug metabolism. Erythromycin appears to be a much weaker inhibitor of drug metabolism. There are numerous reports describing apparent interactions of erythromycin with theophylline and a lesser number of reports dealing with carbamazepine, warfarin methylprednisolone and digoxin. There are sufficient data to suggest that erythromycin can, in some individuals, inhibit the elimination of methylprednisolone, theophylline, carbamazepine and warfarin. The mean change in drug clearance is about 20 to 25% in most cases, with some patients having a much larger change than others. Like tetracycline, erythromycin also appears to have the potential for increasing the bioavailability of digoxin in patients who excrete high amounts of reduced digoxin metabolites, apparently through destruction of the gut flora that form these compounds. Concurrent administration of triacetyloleandomycin with drugs whose metabolism is known to be affected or that could potentially be affected

  11. 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

  12. 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.

  13. Temporal evolution in PPCP removal from urban wastewater by constructed wetlands of different configuration: a medium-term study.

    Science.gov (United States)

    Reyes-Contreras, Carolina; Hijosa-Valsero, María; Sidrach-Cardona, Ricardo; Bayona, Josep M; Bécares, Eloy

    2012-06-01

    Pharmaceuticals and personal care products (PPCPs) are widely distributed in urban wastewaters and can be removed to some extent by constructed wetlands (CWs). The medium-term (3-5 years) behaviour of these systems regarding PPCP removal is still unknown. Seven mesocosm-scale (1 m(2)) CWs of different configurations were operated outdoors for 39 months under the same conditions to assess their PPCP removal ability and temporal evolution. CWs differed in some design parameters, namely plant presence, species chosen (Typha angustifolia vs Phragmites australis), flow configuration and presence/absence of gravel bed (floating macrophytes surface flow, FM-SF; free-water surface flow, FW-SF; free-water subsurface flow, FW-SSF; or conventional horizontal subsurface flow, SSF). PPCP efficiencies decreased throughout time and performance differences among CWs disappeared with the systems aging. This could be due to a homogenization process in the systems caused by detrimental factors like saturation, clogging and shading. Winter efficiencies were lower than summer ones for salicylic acid, caffeine, methyl dihydrojasmonate, galaxolide and tonalide, and seasonal biological activities seem key factors to explain this fact. Maximal removal efficiencies were achieved in an unplanted-FW-SSF for ketoprofen (47-81%), naproxen (58-81%) and salicylic acid (76-98%); in an unplanted-SSF for caffeine (65-99%); in a Phragmites-FM-SF for ibuprofen (49-96%) and diclofenac (16-68%); in a Typha-FM-SF for carbamazepine (35-71%); and in a Typha-FW-SSF for methyl dihydrojasmonate (71-96%), galaxolide (67-82%) and tonalide (55-74%). Photodegradation could be involved in ketoprofen, naproxen, ibuprofen and diclofenac removal. Carbamazepine and diclofenac were moderately removed by the most efficient CWs studied. Carbamazepine might be eliminated by vegetal uptake. PMID:22436587

  14. 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

  15. 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.

  16. Pharmacokinetic interactions with calcium channel antagonists (Part II).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-12-01

    Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity. Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents. PMID:1782739

  17. Analysis of Drugs of Abuse in Anonymously Collected Urine and Soil samples from a Music Festival in Scandinavia

    DEFF Research Database (Denmark)

    Mardal, Marie; Ramin, Pedram; Plósz, Benedek G.;

    -MS Results: In the urine samples, the following compounds (and their metabolites) could be detected: cocaine (in 13 samples), levamisole (11), MDMA (9), amphetamine (2), and methamphetamine (2). Furthermore, therapeutic drugs such as metoprolol, carbamazepine, citalopram, quetiapine, methylphenidate...... be detected besides several therapeutic drugs: cocaine (9), MDMA (7), sildenafil (2), ketamine (1), amphetamine (1), and oxycodone (1). Conclusions: NPS were detected neither in urine nor in soil samples. This might be due to low concentrations based on their negligible consumption at the studied festival...

  18. 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...... 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...

  19. Fate of pharmaceuticals and pesticides in fly larvae composting.

    Science.gov (United States)

    Lalander, C; Senecal, J; Gros Calvo, M; Ahrens, L; Josefsson, S; Wiberg, K; Vinnerås, B

    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 (pesticides into the environment. PMID:27177134

  20. [Drugs from the classes of tricyclic antidepressives and antiepileptics, nitrosatable under simulated human gastric conditions].

    Science.gov (United States)

    Ziebarth, D; Schramm, T; Töppel, A

    1989-01-01

    The nitrosatability of Pryleugan (imipramine), Herphonal (trimipramine), and Finlepsin (carbamazepine) was investigated under simulated human gastric conditions using a colorimetric measuring method. All of them proved to be nitrosatable even at very low nitrite concentrations. In the presence of ascorbic acid, the formation of N-nitroso compounds under model conditions was inhibited markedly. N-nitroso-dihydrodibenzazepine and N-nitroso-dibenzazepine could be identified by thin layer chromatography as main products. The biological effects of these N-nitroso compounds are not known up to now. PMID:2802933

  1. [Quantitative EEG analysis of a single dose of psychotropic drugs in healthy probands].

    Science.gov (United States)

    Fischer, W; Streubel, F R; Heydenreich, F; Rabending, G

    1986-08-01

    In a series of 74 experiments in a double blind study, 25 healthy test persons were medicated with a single dose of Clomipramin, Desipramin, Imipramin, Diazepam, Carbamazepin, Haloperidol, and a placebo. At the end of one hour, and again at the end of three hours, an EEG was made whose frequency analysis revealed significant changes in about half the test persons. The antidepressives induced an increase in the theta waves, the slow alpha waves, and the slow beta waves, and a decrease in the fast alpha waves. The factors influencing the EEG are discussed. PMID:3786575

  2. 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

  3. 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.

  4. 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...... was significantly longer than that of the age-matched controls. The nonpainful-side latency correlated significantly with the carbamazepine dose. Conclusions: LEP detect severe impairment of the nociceptive afferent system on the painful side of patients with idiopathic as well as symptomatic trigeminal neuralgia...

  5. [Music as an uninvited guest: the auditive variant of the Charles Bonnet syndrome].

    Science.gov (United States)

    Tuerlings, J H A M; Wijnen, H; Boerman, R; Verwey, B

    2009-01-01

    Visually handicapped patients can be tormented by complex visual hallucinations (Charles Bonnet syndrome). Likewise, deaf patients and patients with impaired hearing can be plagued by auditory hallucinations, mostly involving music. Our article focuses on three female patients who suffered from musical hallucinations. In one of these patients the hallucinations ceased when her hearing was restored. In the second patient the hallucinations ceased when carbamazepine was prescribed. Quetiapine reduced the musical hallucinations in the third patient. The differential diagnoses and therapeutic options are discussed. PMID:19904711

  6. Medico-legal investigation of narcotics & other drug involved deaths

    Directory of Open Access Journals (Sweden)

    Tofighi H

    1994-04-01

    Full Text Available Today narcotics and other drugs have become the major cause of poisoning in big cities of Iran. Typical study of 50 drug-related deaths caused by use of narcotics, phenobarbital, tricyclic antiderpressants, meprobamate, aspirin, diazepam, chloropromazine, phenytoin, carbamazepine and propranolole, alone or with other drugs and toxic substances is described. This study covered the following topics: age, sex, pathological examination, autopsy cause of death, medical care prior to death. In toxicological examinations, samples from stomach content, liver, kidney, findings, urine and blood samples were analysed by TLC, GC, Emit d.a.u. assay and colour test methods

  7. Removal and fate of micropollutants in a sponge-based moving bed bioreactor.

    Science.gov (United States)

    Luo, Yunlong; Guo, Wenshan; Ngo, Huu Hao; Nghiem, Long Duc; Hai, Faisal Ibney; Kang, Jinguo; Xia, Siqing; Zhang, Zhiqiang; Price, William Evan

    2014-05-01

    This study investigated the removal of micropollutants using polyurethane sponge as attached-growth carrier. Batch experiments demonstrated that micropollutants could adsorb to non-acclimatized sponge cubes to varying extents. Acclimatized sponge showed significantly enhanced removal of some less hydrophobic compounds (log Dmicropollutants. Particularly, carbamazepine, ketoprofen and pentachlorophenol were found at high concentrations (7.87, 6.05 and 5.55 μg/g, respectively) on suspended biosolids. As a whole, the effectiveness of MBBR for micropollutant removal was comparable with those of activated sludge processes and MBRs. PMID:24658104

  8. Can the clinical course of cancer be influenced by non-antineoplastic drugs?

    OpenAIRE

    Brandes, L. J.; Friesen, L A

    1995-01-01

    Laboratory and anecdotal clinical evidence suggests that some common non-antineoplastic drugs may affect the course of cancer. The authors present two cases that appear to be consistent with such a possibility: that of a 63-year-old woman in whom a high-grade angiosarcoma of the forehead improved after discontinuation of lithium therapy and then progressed rapidly when treatment with carbamazepine was started, and that of a 74-year-old woman with metastatic adenocarcinoma of the colon that re...

  9. Comparison Between Ionizing and Non-Ionizing Radiation Technologies for Wastewater Remediation

    International Nuclear Information System (INIS)

    A study on the decomposition of a surfactant (SDBS) and of four emerging pollutants (ofloxacin, carbamazepine, benzophenone-3, benzophenenone-4) in a multicomponent system is presented. These pollutants are decomposed in water by a few types of Advanced Oxidation Processes. The remediation methods included UV and γ-rays, all running in atmospheric conditions. It is shown that UV degradation methods can be improved by adding a photocatalyst (TiO2), or a radical mediator (H2O2). The processes were monitored step by step, by determining the concentration of pollutants by UV, HPLC and a specific surfactant selective kit, and measuring the total organic carbon content. (author)

  10. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

    DEFF Research Database (Denmark)

    Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

    2008-01-01

    Antiepileptic drugs and epilepsy are often associated with sexual disorder in women such as hyperandrogenism, menstrual disorders and ovarian cysts. In children, until puberty, a hormone imbalance may influence many aspects of development, e.g. growth and sexual maturation. The aromatase complex ...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  11. 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

  12. 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.;

    Dosing of methanol or ethanol is a common practice in post-denitrification steps during wastewater treatment by MBBR technology. The carbon-dosage impact on micro- pollutants removal, in terms of type (methanol or ethanol) and concentration was investigated. First, with continuous operation......, 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...

  13. [Update on the management of trigeminal neuralgia].

    Science.gov (United States)

    Alcántara Montero, A; Sánchez Carnerero, C I

    2016-01-01

    Trigeminal neuralgia is one of the most severe facial pain syndromes. The annual incidence varies between 4-13% and has a significant effect on patient quality of life. The initial treatment of trigeminal neuralgia is pharmacological, and although other drugs have demonstrated efficacy, albeit in more limited form, carbamazepine is the only drug with sufficient level of evidence. When medical treatment fails, surgery should be considered and can opt for open surgery or minimally invasive percutaneous techniques. This paper reviews the medical and surgical therapeutic options for the treatment of trigeminal neuralgia, based on current available evidence. PMID:26643391

  14. Neurogenic benign fasciculations, pseudomyotonia, and pseudotetany. A disease in search of a name.

    Science.gov (United States)

    Coërs, C; Telerman-Toppet, N; Durdu, J

    1981-05-01

    We studied two patients with abnormal spontaneous muscular activity. The first had widespread fasciculations, painful spasms, delayed muscular relaxation, and hyperhidrosis. Improvement occurred after several years. The second case had generalized paresthesia, mild stiffness, a positive result from Trusseau's test, and was relieved by administration of carbamazepine. Both patients had abnormal conduction velocity. Examination of muscle biopsy specimens disclosed fiber type grouping and increased collateral ramification of motor axons. These observations exemplify symptoms and signs that resemble those of myotonia and tetany and occasionally occur in partial denervation. they provide additional evidence of the neurogenic nature of Isaacs-Mertens syndrome. PMID:7224912

  15. 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....

  16. Design and synthesis of some novel 4-(4-substituted aryl semicarbazones as anticonvulsant agents

    Directory of Open Access Journals (Sweden)

    Singh Anita

    2010-01-01

    Full Text Available In the present study, a series of 4-(4-substituted aryl semicarbazones were synthesized from substituted anilines and subsequently evaluated for their anticonvulsant activities. The anticonvulsant activities were established by the anticonvulsant drug development (ADD programme NIH, USA using experimental animal, adult male FCM mice (20-25 g and adult Sprague-Dawley rats (100-150 g and screened against electroshock seizure, subcutaneous metrazole and minimal neurotoxicity tests in mice. Compound 7 was found equipotent to carbamazepine in both MES and ScPTZ tests. This study has highlighted the importance of distal alkyl chain which influences the anticonvulsant activity.

  17. Determination of human pharmaceuticals in pre- and post-sewage treatment

    Science.gov (United States)

    Tahrim, Nurfaizah Abu; Abdullah, Md. Pauzi; Aziz, Yang Farina Abdul

    2013-11-01

    In this present work, an analytical method based on solid phase extraction (SPE) followed by liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS) in positive electrospray ionisation mode was successfully applied to real samples for the determination of human pharmaceuticals in pre- and post-sewage treatment samples. The ten target compounds selected in this study include acetaminophen, theophylline, caffeine, metoprolol, sulfamethoxazole, carbamazepine, prednisolone, ketoprofen, norgestrel and simvastatin. Acetaminophen, theophylline and caffeine were present at all five raw sewage samples. In addition, this work provides the first report on the investigation and detection of theophylline in sewage treatment plant (STP) samples in Malaysia.

  18. Intermittent hypoglossal nerve palsy caused by a calcified persistent hypoglossal artery: an uncommon neurovascular compression syndrome.

    Science.gov (United States)

    Meila, Dan; Wetter, Axel; Brassel, Friedhelm; Nacimiento, Wilhelm

    2012-12-15

    Neurovascular compression is assumed to cause symptoms like trigeminal neuralgia, hemifacial spasm and vestibular paroxysmia. We present a patient with recurrent episodes of transient dysarthria due to isolated right hypoglossal nerve (HN) palsy. We describe the first case of a calcified persistent hypoglossal artery (PHA) as the putative cause of a hypoglossal neurovascular compression syndrome. Our patient received a daily low-dose medication of carbamazepine resulting in complete relief of symptoms. In conclusion, PHA is not only an anatomic variation but also a possible cause of a neurovascular compression syndrome leading to intermittent HN palsy. PMID:23020989

  19. 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

    Occurrence and removal efficiencies of 13 pharmaceuticals and personal care products (PPCPs) as well as BOD5, TSS and NH4þ were evaluated for the first time in thirteen onsite household secondary wastewater treatment systems, including two compact biofilters followed by Filtralite-P filter units......, 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...

  20. Drug-Induced Bullous Sweet Syndrome with Multiple Autoimmune Features

    Directory of Open Access Journals (Sweden)

    Jared J. Lund

    2010-01-01

    Full Text Available Sweet syndrome (SS (Acute Febrile Neutrophilic Dermatosis has been reported in association with autoimmune phenomena including relapsing polychondritis, drug-induced lupus, and the development of antineutrophil cytoplasmic antibodies (ANCAs. However, a combination of these autoimmune features has not been reported. Herein, we report a case of drug-induced bullous SS with ocular and mucosal involvement, glomerulonephritis, and multiple autoimmune features including clinical polychondritis with antitype II collagen antibodies, ANCAs, antinuclear (HEp-2, and antihistone antibodies in a patient on hydralazine and carbamazepine.

  1. 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.

  2. Behaviour of pharmaceuticals and psychotic drugs in conventional and advanced wastewater treatments

    International Nuclear Information System (INIS)

    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.

  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. Adverse Effects in the Pharmacologic Management of Bipolar Disorder During Pregnancy.

    Science.gov (United States)

    Hogan, Charlotte S; Freeman, Marlene P

    2016-09-01

    Management of bipolar disorder during pregnancy often involves medications with potential adverse effects, including risks to the mother and fetus. Although some specifics are known, many medications continue to have incompletely characterized reproductive safety profiles. Women with bipolar disorder who are planning pregnancy face challenging decisions about their treatment; careful risk-benefit discussions are necessary. With the goal of further informing these discussions, this article reviews the data currently available regarding medication safety in the management of bipolar disorder during pregnancy, with specific attention to lithium, valproic acid, lamotrigine, carbamazepine, and antipsychotic medications. PMID:27514299

  5. pH-Triggered Molecular Alignment for Reproducible SERS Detection via an AuNP/Nanocellulose Platform

    OpenAIRE

    Haoran Wei; Vikesland, Peter J.

    2015-01-01

    The low affinity of neutral and hydrophobic molecules towards noble metal surfaces hinders their detection by surface-enhanced Raman spectroscopy (SERS). Herein, we present a method to enhance gold nanoparticle (AuNP) surface affinity by lowering the suspension pH below the analyte pKa. We developed an AuNP/bacterial cellulose (BC) nanocomposite platform and applied it to two common pollutants, carbamazepine (CBZ) and atrazine (ATZ) with pKa values of 2.3 and 1.7, respectively. Simple mixing ...

  6. Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2012-01-01

    Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

  7. 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.

  8. 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.

  9. Characterization of pharmaceutically active compounds in Dongting Lake, China: Occurrence, chiral profiling and environmental risk.

    Science.gov (United States)

    Ma, Ruixue; Wang, Bin; Lu, Shaoyong; Zhang, Yizhe; Yin, Lina; Huang, Jun; Deng, Shubo; Wang, Yujue; Yu, Gang

    2016-07-01

    Twenty commonly used pharmaceuticals including eight chiral drugs were investigated in Dongting Lake, China. The contamination level was relatively low on a global scale. Twelve pharmaceuticals were identified. The most abundant compound was caffeine followed by diclofenac, DEET, mefenamic acid, fluoxetine, ibuprofen and carbamazepine with mean concentrations from 2.0 to 80.8ngL(-1). Concentrations between East and West Dongting Lake showed spatial difference, with the West Dongting Lake less polluted. The relatively high ratio of caffeine versus carbamazepine (over 50) may indicate there was possible direct discharge of domestic wastewater into the lake. This is the first study presenting a survey allowing for comprehensive analysis of multiclass achiral and chiral pharmaceuticals including beta-blockers, antidepressants and anti-inflammatory drugs in freshwater lake. The enantiomeric compositions presented racemic to weakly enantioselective, with the highest enantiomeric fraction (EF) of 0.63 for fluoxetine. Meanwhile, venlafaxine was identified and evaluated the environment risk in surface water in China for the first time. The results of risk assessment suggested that fluoxetine, venlafaxine and diclofenac acid might pose a significant risk to aquatic organisms in Dongting Lake. The resulting data will be useful to enrich the research of emerging pollutants in freshwater lake and stereochemistry for environment investigations. PMID:27016674

  10. Oxidation of pharmaceutically active compounds by a ligninolytic fungal peroxidase.

    Science.gov (United States)

    Eibes, Gemma; Debernardi, Gianfranco; Feijoo, Gumersindo; Moreira, M Teresa; Lema, Juan M

    2011-06-01

    Pharmaceuticals are an important group of emerging pollutants with increasing interest due to their rising consumption and the evidence for ecotoxicological effects associated to trace amounts in aquatic environments. In this paper, we assessed the potential degradation of a series of pharmaceuticals: antibiotics (sulfamethoxazole), antidepressives (citalopram hydrobromide and fluoxetine hydrochloride), antiepileptics (carbamazepine), anti-inflammatory drugs (diclofenac and naproxen) and estrogen hormones (estrone, 17β-estradiol, 17α-ethinylestradiol) by means of a versatile peroxidase (VP) from the ligninolytic fungus Bjerkandera adusta. The effects of the reaction conditions: VP activity, organic acid concentration and H(2)O(2) addition rate, on the kinetics of the VP based oxidation system were evaluated. Diclofenac and estrogens were completely degraded after only 5-25 min even with a very low VP activity (10 U l(-1)). High degradation percentages (80%) were achieved for sulfamethoxazole and naproxen. Low or undetectable removal yields were observed for citalopram (up to 18%), fluoxetine (lower than 10%) and carbamazepine (not degraded). PMID:20972884

  11. 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.

  12. 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.

  13. 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.

  14. Removal of pharmaceutically active compounds (PhACs) and toxicological response of Cyperus alternifolius exposed to PhACs in microcosm constructed wetlands.

    Science.gov (United States)

    Yan, Qing; Feng, Guozhong; Gao, Xu; Sun, Chengxiao; Guo, Jin-song; Zhu, Zhiwei

    2016-01-15

    This study investigated the effects of selected four pharmaceutically active compounds (PhACs) (carbamazepine, sulfamethoxazole, ofloxacin, and roxithromycin) on the photosynthesis and antioxidant enzymes of Cyperus alternifolius in constructed wetlands (CWs). Moreover, the removal and kinetics of PhACs in CWs were evaluated to explore the related removal mechanisms. Results showed that C. alternifolius can uptake and withstand certain PhACs. The PhAC tolerance of C. alternifolius might be attributed to their capacity to maintain relatively normal photosynthetic activity and elevated antioxidative defense. CWs offered comparable or even higher removal efficiencies for the selected PhACs compared with conventional WWTPs. The removal of the target PhACs was enhanced in the planted CWs versus the unplanted CWs mostly because of plant uptake and rhizosphere effects. In particular, carbamazepine, which is considered the most recalcitrant of the PhACs, was significantly reduced (p<0.05). The removal of target PhACs fitted into two distinct periods. The initial fast step (within the first 2 h) was essentially attributed to the adsorption onto the CW medium surface. The subsequent slow process (2-12 h) closely followed first-order kinetics probably because of the interaction between microorganisms and plants. The obtained results indicate that C. alternifolius can phytoremediate PhAC-contaminated waters in CWs. PMID:26465971

  15. 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.

  16. 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.

  17. The effects of pharmaceuticals on the regeneration of the cnidarian, Hydra attenuata.

    Science.gov (United States)

    Quinn, Brian; Gagné, François; Blaise, Christian

    2008-08-25

    The Hydra attenuata regeneration assay was used to identify the teratogenic potential of 10 pharmaceuticals identified in effluent from a large city wastewater treatment plant (WWTP). Three types of solvents were used to solubilise the pharmaceuticals (DMSO, acetone and ethanol), at concentrations determined to have no significant effect on measured endpoints. On the one hand, regeneration was significantly inhibited at (nominal) concentrations of 1, 5 and 1 mg/L for gemfibrozil, ibuprofen and naproxen respectively and at the higher concentration of 50 mg/L for bezafibrate and trimethoprim. On the other hand, carbamazepine and the antibiotics sulfapyridine, oxytetracycline and novobiocin significantly increased regeneration at 25, 5, 50 and 50 mg/L respectively. Relatively high IC50 values of 0.9, 3.84, 4.9 and 22.5 mg/L were calculated for gemfibrozil, ibuprofen, naproxen and bezafibrate, respectively. However when subjected to tier two toxicity assessment under EU regulatory guidance using environmentally relevant concentrations a MEC/PNEC value>1 was calculated for gemfibrozil, ibuprofen and naproxen indicating teratogenic potential and the necessity for further tier three assessment. A toxicity index (TI) was also calculated using three different techniques, with TI values>3 (indicating teratogenic potential) found for gemfibrozil, ibuprofen, naproxen and bezafibrate and >1 (indicating a weak teratogenic potential) found for carbamazepine. These results are discussed in the context of their environmental relevance and toxic potential. PMID:18538376

  18. 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.

  19. Leaching of pharmaceuticals and personal care products in turfgrass soils during recycled water irrigation.

    Science.gov (United States)

    Bondarenko, S; Gan, J; Ernst, F; Green, R; Baird, J; McCullough, M

    2012-01-01

    An important beneficial reuse of treated wastewater (recycled water) in arid and semiarid regions is landscape irrigation. However, the environmental fate, especially groundwater contamination potential, of trace contaminants such as pharmaceuticals and personal care products (PPCPs) is a significant concern that can hinder the acceptance and adoption of such reuses. In this study, we irrigated mature turfgrass plots with nonspiked tertiary treated wastewater for over 6 mo at 100 or 130% of the reference evapotranspiration rate (ETo) and collected leachate water at the 90-cm depth on a weekly basis. In the recycled water, all 14 target PPCPs were consistently found, and the mean levels of atenolol, gemfibrozil, meprobamate, carbamazepine, and sulfamethoxazole were above 100 ng L. However, only five compounds were detected in the leachate at trace levels. Trimethoprim and primidone were frequently found, whereas the detection of sulfamethoxazole, meprobamate and carbamazepine was less frequent (meprobamate. The majority of the target PPCPs were completely removed. Given that the irrigation rates were higher than normal, this study clearly demonstrated the efficacy of turfgrass systems in attenuating PPCPs during recycled water irrigation. However, it is also apparent that some PPCPs are more susceptible to leaching than others, and these PPCPs thus merit further research attention. PMID:22751071

  20. Removal of pharmaceuticals and personal care products in a membrane bioreactor wastewater treatment plant.

    Science.gov (United States)

    Kim, M; Guerra, P; Shah, A; Parsa, M; Alaee, M; Smyth, S A

    2014-01-01

    Ninety-nine pharmaceuticals and personal care products (PPCPs) were analyzed in influent, final effluent, and biosolids samples from a wastewater treatment plant employing a membrane bioreactor (MBR). High concentrations in influent were found for acetaminophen, caffeine, metformin, 2-hydroxy-ibuprofen, paraxanthine, ibuprofen, and naproxen (10(4)-10(5) ng/L). Final effluents contained clarithromycin, metformin, atenolol, carbamazepine, and trimethoprim (>500 ng/L) at the highest concentrations, while triclosan, ciprofloxacin, norfloxacin, triclocarban, metformin, caffeine, ofloxacin, and paraxanthine were found at high concentrations in biosolids (>10(3) ng/g dry weight). PPCP removals varied from -34% to >99% and 23 PPCPs had ≥90% removal. Of the studied PPCPs, 26 compounds have been rarely or never studied in previous membrane bioreactor (MBR) investigations. The removal pathway showed that acetaminophen, 2-hydroxy-ibuprofen, naproxen, ibuprofen, codeine, metformin, enalapril, atorvastatin, caffeine, paraxanthine, and cotinine exhibited high degradation/transformation. PPCPs showing strong sorption to solids included triclocarban, triclosan, miconazole, tetracycline, 4-epitetracycline, norfloxacin, ciprofloxacin, doxycycline, paroxetine, and ofloxacin. Trimethoprim, oxycodone, clarithromycin, thiabendazole, hydrochlorothiazide, erythromycin-H2O, carbamazepine, meprobamate, and propranolol were not removed during treatment, and clarithromycin was even formed during treatment. This investigation extended our understanding of the occurrence and fate of PPCPs in an MBR process through the analysis of the largest number of compounds in an MBR study to date. PMID:24901615

  1. 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. PMID:26877044

  2. Pharmaceuticals as indictors of sewage-influenced groundwater

    Science.gov (United States)

    Müller, Beate; Scheytt, Traugott; Asbrand, Martin; de Casas, Andrea Mross

    2012-09-01

    A set of human pharmaceuticals enables identification of groundwater that is influenced by sewage and provides information on the time of recharge. As the consumption rates of the investigated pharmaceuticals have changed over time, so too has the composition of the sewage. At the study area, south of Berlin (Germany), irrigation was performed as a method of wastewater clean-up at sewage irrigation farms until the early 1990s. Today, treated wastewater is discharged into the surface-water-stream Nuthegraben. Groundwater and surface-water samples were analyzed for the pharmaceutical substances clofibric acid, bezafibrate, diclofenac, carbamazepine and primidone, the main ions and organic carbon. The pharmaceutical substances were detected at concentrations up to microgram-per-liter level in groundwater and surface-water samples from the Nuthegraben Lowland area and from the former irrigation farms. Concentrations detected in groundwater are generally much lower than in surface water and there is significant variation in the distribution of pharmaceutical concentrations in groundwater. Groundwater influenced by the irrigation of sewage water shows higher primidone and clofibric-acid concentrations. Groundwater influenced by recent discharge of treated sewage water into the surface water shows high carbamazepine concentrations while concentrations of primidone and clofibric acid are low.

  3. 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 (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. PMID:25196960

  4. 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.

  5. 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.

  6. Irrigation of root vegetables with treated wastewater: evaluating uptake of pharmaceuticals and the associated human health risks.

    Science.gov (United States)

    Malchi, Tomer; Maor, Yehoshua; Tadmor, Galit; Shenker, Moshe; Chefetz, Benny

    2014-08-19

    To meet mounting water demands, treated wastewater has become an important source of irrigation. Thus, contamination of treated wastewater by pharmaceutical compounds (PCs) and the fate of these compounds in the agricultural environment are of increasing concern. This field study aimed to quantify PC uptake by treated wastewater-irrigated root crops (carrots and sweet potatoes) grown in lysimeters and to evaluate potential risks. In both crops, the nonionic PCs (carbamazepine, caffeine, and lamotrigine) were detected at significantly higher concentrations than ionic PCs (metoprolol, bezafibrate, clofibric acid, diclofenac, gemfibrozil, ibuprofen, ketoprofen, naproxen, sulfamethoxazole, and sildenafil). PCs in leaves were found at higher concentrations than in the roots. Carbamazepine metabolites were found mainly in the leaves, where the concentration of the metabolite 10,11-epoxycarbamazepine was significantly higher than the parent compound. The health risk associated with consumption of wastewater-irrigated root vegetables was estimated using the threshold of toxicological concern (TTC) approach. Our data show that the TTC value of lamotrigine can be reached for a child at a daily consumption of half a carrot (∼60 g). This study highlights that certain PCs accumulated in edible organs at concentrations above the TTC value should be categorized as contaminants of emerging concern.

  7. Anticonvulsants in the treatment of aggression in the demented elderly: an update

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    Gonzalez-Pinto Ana

    2009-06-01

    Full Text Available Abstract Introduction Complex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity. Methods Commonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate. Results To date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate. Conclusion So far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.

  8. 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. PMID:26773491

  9. Temperature dependent redox zonation and attenuation of wastewater-derived organic micropollutants in the hyporheic zone.

    Science.gov (United States)

    Burke, Victoria; Greskowiak, Janek; Asmuß, Tina; Bremermann, Rebecca; Taute, Thomas; Massmann, Gudrun

    2014-06-01

    The hyporheic zone - a spatially fluctuating ecotone connecting surface water and groundwater - is considered to be highly reactive with regard to the attenuation of organic micropollutants. In the course of the presented study an undisturbed sediment core was taken from the infiltration zone of a bank filtration site in Berlin and operated under controlled laboratory conditions with wastewater-influenced surface water at two different temperatures, simulating winter and summer conditions. The aim was to evaluate the fate of site-relevant micropollutants, namely metoprolol, iopromide, diclofenac, carbamazepine, acesulfame, tolyltriazole, benzotriazole, phenazone and two phenazone type metabolites, within the first meter of infiltration dependent on the prevailing temperature. A change in temperature resulted in a development of significantly distinct redox conditions. Both temperature dependencies and related redox dependencies were identified for all micropollutants except for benzotriazole and carbamazepine, which behaved persistent under all conditions. For the remaining compounds degradation rate constants generally decreased from warm and oxic/penoxic/suboxic over cold and oxic/penoxic to warm and manganese reducing (transition zone). Individual degradation rate constants ranged from 0 (e.g. diclofenac, acesulfame and tolyltriazole in the transition zone) to 1.4×10(-4)s(-1) for metoprolol under warm conditions within the oxic to suboxic zone. PMID:24642095

  10. Solar photo-Fenton using peroxymonosulfate for organic micropollutants removal from domestic wastewater: comparison with heterogeneous TiO₂ photocatalysis.

    Science.gov (United States)

    Ahmed, Moussa Mahdi; Brienza, Monica; Goetz, Vincent; Chiron, Serge

    2014-12-01

    This work aims at decontaminating biologically treated domestic wastewater effluents from organic micropollutants by sulfate radical based (SO4(-)) homogeneous photo-Fenton involving peroxymonosulfate as an oxidant, ferrous iron (Fe(II)) as a catalyst and simulated solar irradiation as a light source. This oxidative system was evaluated by using several probe compounds belonging to pesticides (bifenthrin, mesotrione and clothianidin) and pharmaceuticals (diclofenac, sulfamethoxazole and carbamazepine) classes and its kinetic efficiency was compared to that to the well known UV-Vis/TiO2 heterogeneous photocatalysis. Except for carbamazepine, apparent kinetic rate constants were always 10 times higher in PMS/Fe(II)/UV-Vis than in TiO2/UV-Vis system and more than 70% of total organic carbon abatement was reached in less than one hour treatment. Hydroxyl radical (OH) and SO4(-) reactivity was investigated using mesotrione as a probe compound through by-products identification by liquid chromatography-high resolution-mass spectrometry and transformation pathways elucidation. In addition to two OH based transformation pathways, a specific SO4(-) transformation pathway which first involved degradation through one electron transfer oxidation processes followed by decarboxylation were probably responsible for mesotrione degradation kinetic improvement upon UV-Vis/PMS/Fe(II) system in comparison to UVVis/TiO2 system. PMID:25108605

  11. Degradation of PPCPs in activated sludge from different WWTPs in Denmark.

    Science.gov (United States)

    Chen, Xijuan; Vollertsen, Jes; Nielsen, Jeppe Lund; Dall, Agnieszka Gieraltowska; Bester, Kai

    2015-12-01

    Pharmaceuticals and Personal care products (PPCPs) are often found in effluents from wastewater treatment plants (WWTPs) due to insufficient removal during wastewater treatment processes. To understand the factors affecting the removal of PPCPs in classical activated sludge WWTPs, the present study 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 and Carbamazepine were found to be persistent in the systems. Degradation rate constants were calculated as 0.0026-0.0407 for NSAID pharmaceuticals and 0.0022-0.0065 for triclosan. No relationships were observed between degradation rates and biomass concentrations in the diverse sludges. However, for the investigated PPCPs, the optimal SRT was within 14-20 days (for these values degradation of these PPCPs was the most efficient). Though all of these parameters influence the degradation rate, none of them seems to be overall decisive. These observations indicate that the biological composition of the sludge is more important than the design parameters of the respective treatment plant. PMID:26407712

  12. Pharmaceuticals, Their Metabolites, and Other Polar Pollutants in Field-Grown Vegetables Irrigated with Treated Municipal Wastewater.

    Science.gov (United States)

    Riemenschneider, Christina; Al-Raggad, Marwan; Moeder, Monika; Seiwert, Bettina; Salameh, Elias; Reemtsma, Thorsten

    2016-07-27

    The reuse of treated municipal wastewater for crop irrigation is a necessity in arid and semiarid regions but a potential entrance for emerging contaminants into the food chain. However, little attention has yet been paid to the detection of micropollutants and possible metabolites in vegetables grown under realistic field conditions. In this study, the uptake of 28 micropollutants and carbamazepine metabolites in 10 different field-grown vegetable species (among them carrot, lettuce, potato, and zucchini) from Jordan was studied. A total of 12 micropollutants and six carbamazepine metabolites, four of which have never been analyzed before in plant-uptake studies, could be detected in all of the samples in concentrations ranging from 1.7 to 216 ng per g of dry weight. In edible tissues, the total concentration of micropollutants decreased in the order of leafy (247-533) > root (73-126) > fruit-bearing (5-76 ng per g of dry weight) vegetables. A preliminary health-risk assessment for nine compounds according to the TTC concept shows no risk for seven of the micropollutats; for ciprofloxacin and 10,11-epoxycarbamazepine, however, more-specific toxicity data would be required for a refined risk assessment. PMID:27378214

  13. Pharmacokinetics and drug interactions of eslicarbazepine acetate.

    Science.gov (United States)

    Bialer, Meir; Soares-da-Silva, Patricio

    2012-06-01

    Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) approved in Europe since 2009 that was found to be efficacious and well tolerated in a phase III clinical program in adult patients with partial onset seizures previously not controlled with treatment with one to three AEDs, including carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally different at the 10,11 position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine-10,11-epoxide. Unlike OXC, which is metabolized to both eslicarbazepine and (R)-licarbazepine, ESL is extensively converted to eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral administration is approximately 94% of the parent dose, with minimal exposure to (R)-licarbazepine and OXC. After ESL oral administration, the effective half-life (t(1/2,eff) ) of eslicarbazepine was 20-24 h, which is approximately two times longer than its terminal half-life (t(1/2)). At clinically relevant doses (400-1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or moderate liver impairment. However, because eslicarbazepine is eliminated primarily (66%) by renal excretion, dose adjustment is recommended for patients with renal impairment. Eslicarbazepine clearance is induced by phenobarbital, phenytoin, and CBZ and it dose-dependently decreases plasma exposure of oral contraceptive and simvastatin. PMID:22612290

  14. 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.

  15. Structural characterization and aging of glassy pharmaceuticals made using acoustic levitation.

    Science.gov (United States)

    Benmore, Chris J; Weber, J K R; Tailor, Amit N; Cherry, Brian R; Yarger, Jeffery L; Mou, Qiushi; Weber, Warner; Neuefeind, Joerg; Byrn, Stephen R

    2013-04-01

    Here, we report the structural characterization of several amorphous drugs made using the method of quenching molten droplets suspended in an acoustic levitator. (13) C NMR, X-ray, and neutron diffraction results are discussed for glassy cinnarizine, carbamazepine, miconazole nitrate, probucol, and clotrimazole. The (13) C NMR results did not find any change in chemical bonding induced by the amorphization process. High-energy X-ray diffraction results were used to characterize the ratio of crystalline to amorphous material present in the glasses over a period of 8 months. All the glasses were stable for at least 6 months except carbamazepine, which has a strong tendency to crystallize within a few months. Neutron and X-ray pair distribution function analyses were applied to the glassy materials, and the results were compared with their crystalline counterparts. The two diffraction techniques yielded similar results in most cases and identified distinct intramolecular and intermolecular correlations. The intramolecular scattering was calculated based on the crystal structure and fit to the measured X-ray structure factor. The resulting intermolecular pair distribution functions revealed broad-nearest and next-nearest neighbor molecule-molecule correlations. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1290-1300, 2013. PMID:23381910

  16. An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells

    International Nuclear Information System (INIS)

    Efficient and accurate safety assessment of compounds is extremely important in the preclinical development of drugs especially when hepatotoxicty is in question. Multiparameter and time resolved assays are expected to greatly improve the prediction of toxicity by assessing complex mechanisms of toxicity. An integrated approach is presented in which Hep G2 cells and primary rat hepatocytes are compared in frequently used cytotoxicity assays for parent compound toxicity. The interassay variability was determined. The cytotoxicity assays were also compared with a reliable alternative time resolved respirometric assay. The set of training compounds consisted of well known hepatotoxins; amiodarone, carbamazepine, clozapine, diclofenac, tacrine, troglitazone and verapamil. The sensitivity of both cell systems in each tested assay was determined. Results show that careful selection of assay parameters and inclusion of a kinetic time resolved assay improves prediction for non-metabolism mediated toxicity using Hep G2 cells as indicated by a sensitivity ratio of 1. The drugs with EC50 values 100 μM or lower were considered toxic. The difference in the sensitivity of the two cell systems to carbamazepine which causes toxicity via reactive metabolites emphasizes the importance of human cell based in-vitro assays. Using the described system, primary rat hepatocytes do not offer advantage over the Hep G2 cells in parent compound toxicity evaluation. Moreover, respiration method is non invasive, highly sensitive and allows following the time course of toxicity. Respiration assay could serve as early indicator of changes that subsequently lead to toxicity.

  17. 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.

  18. Do no harm - But first we need to know more: The case of adverse drug reactions with antiepileptic drugs

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    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.

  19. 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.

  20. Changes of serum and brain tissue contents of IL-1β, IL-6 and TNF-α in rat models of epilepsy

    International Nuclear Information System (INIS)

    Objective: To investigate the neuro-immuno-modulation effect of the cytokines IL-1β, IL-6 and TNF-α as well as the influence of carbamazepine (CBZ) in experimental rat models with epilepsy. Methods: Sixty rat models of epilepsy (KA group) were prepared with intraperitoneal injection of kainic acid (10 mg/kg). Another 60 models (CBZ group) were prepared with the same injection but pretreated with CBZ gavage (45 mg/kg) daily for 7 days. Sixty rats with sham injection and sham gavage were used as controls. In the two model groups, ten animals were sacrificed at each of the time points: 1, 4, 12, 24, 48, 72h after the development of epilepsy and the serum and brain homogenate contents of the cytokines were repeatedly determined with RIA. The same was applied to the control group at the corresponding time point. Results: In the two epileptic models, serum and brain homogenate contents of these cytokines increased gradually and attained peak levels at 24h (TNF-α) or 48h (IL-1β, IL-6). The levels in the KA group at any time point were significantly higher than those in the CBZ group and control group ( P<0.01). Levels in the CBZ group were also significantly higher than those in controls (P<0.05, P<0.01). Conclusion: The immune system was greatly activated in the rat epileptic models, carbamazepine might provide some protective action through immunosuppression. (authors)

  1. 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

    International Nuclear Information System (INIS)

    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 (KOW) and the sediment organic carbon fraction (ƒOC). 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−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

  2. 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.

  3. Occurrence of pharmaceuticals and UV filters in swimming pools and spas.

    Science.gov (United States)

    Ekowati, Yuli; Buttiglieri, Gianluigi; Ferrero, Giuliana; Valle-Sistac, Jennifer; Diaz-Cruz, M Silvía; Barceló, Damià; Petrovic, Mira; Villagrasa, Marta; Kennedy, Maria D; Rodríguez-Roda, Ignasi

    2016-07-01

    The occurrence of 32 pharmaceuticals and 14 UV filters in swimming pools and spas was studied. Fifty-one water samples were collected from 17 pools located in sport centres and hotels in Catalonia, Spain. The samples were analysed by liquid chromatography-tandem mass spectrometry. The pharmaceuticals atenolol, carbamazepine, hydrochlorothiazide, metronidazole, ofloxacin, sulfamethoxazole, acetaminophen, ibuprofen, ketoprofen and phenazone were measured in water samples at concentrations higher than their limit of quantification (LOQ). The highest concentration of any individual pharmaceutical was measured for the diuretic hydrochlorothiazide (904 ng/L). The most frequently detected pharmaceutical was carbamazepine, as it was observed in more than half of all the water samples measured (53 %, 27/51). The UV filters at concentrations higher than LOQ in water samples were BP1, BP2, BP3, BP8, THB, 4DHB, 4MBC, OD-PABA, 1HBT, MeBT and DMeBT. The highest concentration of UV filter observed was 4MBC (69.3 ng/L) while the most frequent UV filters in the samples were 1HBT (59 %, 30/51). The results also showed that pharmaceuticals and UV filters were most frequently found in spas. Finally, from a water treatment technology perspective, the lowest occurrence of pharmaceuticals was in the pools applying sand filters followed by disinfection by sodium hypochlorite, while the lowest occurrence of UV filters was in the pools applying coagulation, sand filtration, UV and salt electrolysis. PMID:27068900

  4. Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tomas Koltai

    2015-07-01

    Full Text Available Objective: To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties. Material and methods: A review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it was tested with this purpose in the experimental and clinical settings. Results: The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole. Each of them are independently described and analyzed. Conclusions: The above mentioned pharmaceuticals have shown anti-metastatic and anti-invasion activity and many of them deserve to be tested in well-planned clinical trials as adjunct therapies for solid tumors and as anti-metastatic agents. Antiepileptic drugs like phenytoin, carbamazepine and valproate and the vasodilator flunarizine emerged as particularly useful for anti-metastatic purposes.

  5. 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.

  6. Volume-selective proton MR spectroscopy for in-vitro quantification of anticonvulsants

    International Nuclear Information System (INIS)

    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.)

  7. 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.

  8. Rejection of pharmaceuticals by forward osmosis membranes.

    Science.gov (United States)

    Jin, Xue; Shan, Junhong; Wang, Can; Wei, Jing; Tang, Chuyang Y

    2012-08-15

    Rejection of four pharmaceutical compounds, carbamazepine, diclofenac, ibuprofen and naproxen, by forward osmosis (FO) membranes was investigated in this study. For the first time, the rejection efficiency of the pharmaceutical compounds was compared between commercial cellulose triacetate (CTA) based membranes and thin film composite (TFC) polyamide based membranes. The rejection behavior was related to membrane interfacial properties, physicochemical characteristics of the pharmaceutical molecules and feed solution pH. TFC polyamide membranes exhibited excellent overall performance, with high water flux, excellent pH stability and great rejection of all pharmaceuticals investigated (>94%). For commercial CTA based FO membranes, hydrophobic interaction between the compounds and membranes exhibited strong influence on their rejection under acidic conditions. The pharmaceuticals rejection was well correlated to their hydrophobicity (log D). Under alkaline conditions, both electrostatic repulsion and size exclusion contributed to the removal of deprotonated molecules. The pharmaceuticals rejection by CTA-HW membrane at pH 8 followed the order: diclofenac (99%)>carbamazepine (95%)>ibuprofen (93%) ≈ naproxen (93%). These results can be important for FO membrane synthesis, modification and their application in water purification. PMID:22640821

  9. 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. PMID:26364268

  10. Mood stabilisers and pregnancy outcomes: a review

    Directory of Open Access Journals (Sweden)

    Costoloni, Giulia

    2014-10-01

    Full Text Available The purpose of this review is to give useful information to guide clinicians when treating pregnant women affected by bipolar disorder. This review focuses on mood stabilizers including lithium, sodium valproate, carbamazepine, oxcarbazepine, gabapentin, lamotrigine and topiramate. Data have been extracted from a MEDLINE search. Data from prospective, retrospective and case-control studies as well as systematic reviews, meta-analysis and data from Pregnancy Registry were included. Major congenital malformations as well as specific malformations were reported for each drug. Preliminary findings seem to identify lamotrigine as one of the safest antiepileptic drugs to be used in pregnancy. Teratogenity risk of topiramate is still largely unknown and there are not enough studies to draw even preliminary conclusions. Preliminary studies failed to report an increased risk for major congenital malformations among gabapentin or oxcarbazepine exposed pregnancies. Even if raising less concern when compared to valproate, carbamazepine should be avoided for its documented teratogenity risk. Valproate seems to be the worst considering major congenital malformations, specific malformations as well as its detrimental effects on neurodevelopment. On the other hand, lithium might be considered a good option when treating pregnant women affected by bipolar disorder. Given the limited research on mood stabilizers in pregnancy, clinicians need to be very careful when treating child bearing age women. Clinicians have to balance the potential teratogenity risk against that of untreated mental illness considering individual circumstances such as severity of illness and risk of relapse.

  11. [Mood stabilisers and pregnancy outcomes - a review].

    Science.gov (United States)

    Costoloni, Giulia; Pierantozzi, Elisa; Goracci, Arianna; Bolognesi, Simone; Fagiolini, Andrea

    2014-01-01

    The purpose of this review is to give useful information to guide clinicians when treating pregnant women affected by bipolar disorder. This review focuses on mood stabilizers including lithium, sodium valproate, carbamazepine, oxcarbazepine, gabapentin, lamotrigine and topiramate. Data have been extracted from a MEDLINE search. Data from prospective, retrospective and case-control studies as well as systematic reviews, meta-analysis and data from Pregnancy Registry were included. Major congenital malformations as well as specific malformations were reported for each drug. Preliminary findings seem to identify lamotrigine as one ofthe safest antiepileptic drugs to be used in pregnancy. Teratogenity risk oftopiramate is still largely unknown and there are not enough studies to draw even preliminary conclusions. Preliminary studies failed to report an increased risk for major congenital malformations among gabapentin or.oxcarbazepine exposed pregnancies. Even if raising less concern when compared to valproate, carbamazepine should be avoided for its documented teratogenity risk. Valproate seems to be the worst considering major congenital malformations, specific malformations as,well as its detrimental effects on neurodevelopment. On the other hand, lithium might be considered a good option when treating pregnant women affected by bipolar disorder. Given the limited research on mood stabilizers in pregnancy, clinicians need to be very careful when treating child bearing age women. Clinicians have to balance the potential teratogenityrisk against that of untreated mental illness considering individual circumstances such as severity of illness and risk of relapse. PMID:25639010

  12. 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.

  13. Transport of four pharmaceuticals in different horizons of three soil types

    Science.gov (United States)

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

    2015-04-01

    Soil structure, which varies in different soil types and the horizons of these soil types, has a significant impact on water flow and contaminant transport in soils. Transport of many contaminants is in addition strongly influenced by their sorption on soil particles. Transport of four pharmaceuticals (sulfamethoxazole, trimethoprim, atenolol and carbamazepine) was studied in soil columns (a diameter of 10.5 cm and a height of 13 cm) taken from all diagnostic horizons of three different soil types (Haplic Luvisol, Greyic Phaeozem and Haplic Cambisol). The irrigation by water contaminated by a mixture of all four compounds followed by ponding infiltration of distilled water was simulated and water outflow and solute concentrations from the bottom of the soil sample was monitored in time. The highest infiltration rates were observed for soil samples from the Bt horizons of the Greyic Phaeozem that exhibited prismatic structure, followed by rates observed in the Ap horizons of the Haplic Luvisol, Greyic Phaeozem and Haplic Cambisol (due to their granular soil structure and presence of root channels). The lowest infiltration rate was measured for the Bw horizon of the Haplic Cambisol, which had a poorly developed soil structure and a low fraction of macropores. Compound discharge was however also highly affected by their sorption on solids. The highest mobility was observed for sulfamethoxazole followed by carbamazepine atenolol and trimethoprim, which corresponds to measured sorption isotherms. Mobility of ionizable compounds in different soil samples was influenced by pH (i.e. degree and form of their ionization) and sites available for absorption. Mobility of sulfamethoxazole decreased with decreasing pH (i.e. the largest sorption measured in horizons of the Haplic Cambisol). While mobility of atenolol and trimethoprim decreased with increasing base cation saturation, and with increasing organic matter content for carbamazepine. As result of both affects (i.e. soil

  14. An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarian, Hydra attenuata.

    Science.gov (United States)

    Quinn, Brian; Gagné, François; Blaise, Christian

    2008-01-25

    Pharmaceuticals previously identified in the effluent from the wastewater treatment plant (WWTP) in Montreal discharging into the St. Lawrence river, were tested for acute and chronic toxicity using the cnidarian Hydra attenuata. Acute toxicity was based on the established technique looking at morphological changes in the Hydra, while recently developed endpoints of feeding behaviour, attachment and growth (hydranth number) were used to measure chronic effects. The compounds under investigation (ibuprofen, naproxen, gemfibrozil, bezafibrate, carbamazepine, sulfamethoxazole, sulfapyridine, oxytetracycline, novobiocin, trimethoprim and caffeine) were tested individually in controlled laboratory exposures with LC(50) and EC(50) results calculated. All compounds tested had relatively high LC(50) values with gemfibrozil, ibuprofen and naproxen having the lowest at 22.36 mg/L and EC(50) values based on morphology of 1.18 to 2.62 mg/L (all concentrations are nominal). The EC(50) values based on feeding were similar to those based on morphology but with increased sensitivity for carbamazepine, bezafibrate and novobiocin. A trend of a reduction in feeding with deterioration in morphology was observed in the Hydra, with the exception of novobiocin, where a lower than expected EC(50) of 13.53 mg/L was found with no negative effect on morphology. Significant reductions in attachment and hydranth number were seen at concentrations of 1 and 5 mg/L for gemfibrozil and ibuprofen respectively. A toxicity threshold (TT) of 320 microg/L was calculated for ibuprofen, only a factor of 10(2) or 10 higher than the concentration found in the effluent in the present study (1.19 mug/L) and in other Canadian effluents studied (22 microg/L [Brun GL, Bernier M, Losier R, Doe K, Jackman P, Lee HB, Pharmaceutically active compounds in Atlantic Canadian sewage treatment plant effluents and receiving waters and potential for environmental effects as measured by acute and chronic aquatic toxicity

  15. 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

  16. 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

  17. 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.

  18. Cocrystal formation in solution: Inducing phase transition by manipulating the amount of cocrystallizing agent

    Science.gov (United States)

    Gagniere, Emilie; Mangin, Denis; Puel, François; Valour, Jean-Pierre; Klein, Jean-Paul; Monnier, Olivier

    2011-02-01

    The purpose of this work was to assess the possibility of inducing solution mediated phase transition (SMPT) by manipulating the amount of the cocrystallizing agent. The cocrystal, composed of an active pharmaceutical ingredient (carbamazepine, CBZ) and its cocrystallizing agent (a vitamin—nicotinamide, NCT), was selected as a model compound. Batch experiments were performed in a stirred vessel. The solute concentrations of both CBZ and NCT were monitored using in situ ATR-FTIR spectroscopy. The introduction of NCT in dry form allowed a shift in the phase diagram, leading to an SMPT from CBZ crystals toward cocrystals. The concentration profiles gave information on the phase transition kinetics, i.e., the kinetics of nucleation, growth and dissolution mechanisms of the solid phases involved. Several situations were analyzed. This procedure could also be used to correct a process deviation that led to CBZ crystals instead of cocrystals.

  19. Follow-up findings in regional cerebral blood flow (r-CBF)-SPECT in a case of idiopathic childhood hemidystonia. Functional neuroimaging and pathophysiological implications

    International Nuclear Information System (INIS)

    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.)

  20. Amino acids as co-amorphous stabilizers for poorly water-soluble drugs - Part 2

    DEFF Research Database (Denmark)

    Löbmann, K.; Laitinen, R.; Strachan, C.;

    2013-01-01

    spectroscopy. Molecular interactions of the drugs carbamazepine and indomethacin with the amino acids arginine, phenylalanine, and tryptophan were investigated. The amino acids were chosen from the biological target site of both drugs and prepared as co-amorphous formulations together with the drugs...... by vibrational ball milling. A detailed analysis of the FTIR spectra of these formulations revealed specific peak shifts in the vibrational modes of functional groups of drug and amino acid, as long as one amino acid from the biological target site was present in the blends. These peak shifts indicate...... that the drugs formed specific molecular interactions (hydrogen bonding and π-π interactions) with the amino acids. In the drug-amino acid mixtures that contained amino acids which were not present at the biological target site, no such interactions were identified. This study shows the potential of amino acids...

  1. 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

    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....... 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...

  2. 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.

  3. [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.

  4. Pharmacogenomic Testing for Neuropsychiatric Drugs: Current Status of Drug Labeling, Guidelines for Using Genetic Information, and Test Options

    Science.gov (United States)

    Drozda, Katarzyna; Müller, Daniel J.; Bishop, Jeffrey R.

    2014-01-01

    Advancements in pharmacogenomics have introduced an increasing number of opportunities to bring personalized medicine into clinical practice. Understanding how and when to use this technology to help guide pharmacotherapy used to treat neuropsychiatric conditions remains a challenge for many clinicians. Currently, guidelines exist to assist clinicians in the use of genetic information for drug selection and/or dosing for the tricyclic antidepressants, carbamazepine, and phenytoin. Additional language in the product labeling suggests that genetic information may also be useful for assessing the starting and target doses, as well as drug interaction potential, for a number of other medications used to treat psychiatric and neurological conditions. In this review, we outline the current status of pharmacogenomic testing for neuropsychiatric drugs as it pertains to information contained in drug labeling, consensus guidelines, and test panels, as well as considerations related to obtaining tests for patients. PMID:24523097

  5. 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

  6. 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.

  7. Decomposition of persistent pharmaceuticals in wastewater by ionizing radiation

    Science.gov (United States)

    Kimura, Atsushi; Osawa, Misako; Taguchi, Mitsumasa

    2012-09-01

    Pharmaceuticals in wastewater were treated by the combined method of activated sludge and ionizing radiation in laboratory scale. Oseltamivir, aspirin, and ibuprofen at 5 μmol dm-3 in wastewater were decomposed by the activated sludge at reaction time for 4 h. Carbamazepine, ketoprofen, mefenamic acid, clofibric acid, and diclofenac were not biodegraded completely, but were eliminated by γ-ray irradiation at 2 kGy. The rate constants of the reactions of these pharmaceuticals with hydroxyl radicals were estimated by the competition reaction method to be 4.0-10×109 mol-1 dm3 s-1. Decompositions of the pharmaceuticals in wastewater by ionizing radiation were simulated by use of the rate constants and the amount of total organic carbon as parameters. Simulation curves of concentrations of these pharmaceuticals as a function of dose described the experimental data, and the required dose for the elimination of them in wastewater by ionizing radiation can be estimated by this simulation.

  8. 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

  9. Quantitative dynamic nuclear polarization‐NMR on blood plasma for assays of drug metabolism

    DEFF Research Database (Denmark)

    Lerche, Mathilde Hauge; Meier, Sebastian; Jensen, Pernille Rose;

    2011-01-01

    ‐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. Copyright...... 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 13C‐carbamazepine and its pharmacologically active metabolite 13C‐carbamazepine‐10,11‐epoxide is 0.08 µg/mL in rabbit blood plasma analyzed by single......‐scan 13C 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...

  10. 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.

  11. [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.

  12. 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.

  13. Modeling Uptake of Selected Pharmaceuticals and Personal Care Products into Food Crops from Biosolids-Amended Soil

    DEFF Research Database (Denmark)

    Prosser, Ryan S.; Trapp, Stefan; Sibley, Paul K.

    2014-01-01

    Biosolids contain a variety of pharmaceuticals and personal care products (PPCPs). Studies have observed the uptake of PPCPs into plants grown in biosolids-amended soils. This study examined the ability of Dynamic Plant Uptake (DPU) model and Biosolids-amended Soil Level IV (BASL4) model to predict...... the concentration of eight PPCPs in the tissue of plants grown in biosolids-amended soil under a number of exposure scenarios. Concentrations in edible tissue predicted by the models were compared to concentrations reported in the literature by calculating estimated human daily intake values for both sets of data...... by a single order of magnitude. DPU predicted concentrations of triclosan, triclocarban, miconazole, carbamazepine, and diphenhydramine in plant tissues that were within an order of magnitude of concentrations reported in the literature. The study also found that more empirical data are needed on the uptake...

  14. 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.

  15. 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 J; Phillips, Patrick J; Colella, Kaitlyn M; Fisher, Shawn C; Tagliaferri, Tristen; Foreman, William T; Furlong, Edward T

    2016-06-30

    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. PMID:27261279

  16. 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.

  17. 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.

  18. Focal neuromyotonia as a presenting feature of lumbosacral radiculopathy

    Directory of Open Access Journals (Sweden)

    Tushar Premraj Raut

    2013-01-01

    Full Text Available Neuromyotonia is characterized by motor, sensory, and autonomic features along with characteristic electrophysiologic findings, resulting from hyperexcitability of the peripheral nerves. We describe the case of a 36-year-old man, who presented with the disabling symptoms suggestive of focal neuromyotonia involving both the lower limbs. His neurological examination revealed continuous rippling of both the calf muscles with normal power, reflexes, and sensory examination. Electrophysiology revealed spontaneous activity in the form of doublets, triplets, and neuromyotonic discharges along with the neurogenic motor unit potentials in bilateral L5, S1 innervated muscles. Magnetic resonance imaging lumbosacral spine revealed lumbar intervertebral disc protrusion with severe foraminal and spinal canal stenosis. Patient had good response to steroids and carbamazepine. The disabling focal neuromyotonia, occurring as a result of chronic active radiculopathy, brought the patient to medical attention. Patient responded to medical management.

  19. 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.

  20. Polar organic micropollutants in the coastal environment of different marine systems.

    Science.gov (United States)

    Nödler, Karsten; Voutsa, Dimitra; Licha, Tobias

    2014-08-15

    Polar anthropogenic organic micropollutants are frequently detected in freshwater and discharged on large scale into marine systems. In this work the results of 153 samples collected from the shorelines of the Baltic Sea (Germany), Northern Adriatic Sea (Italy), Aegean Sea and Dardanelles (Greece & Turkey), San Francisco Bay (USA), Pacific Ocean (USA), Mediterranean Sea (Israel), and Balearic Sea (Spain) are presented. The samples were analyzed for various classes of micropollutants such as pharmaceuticals, corrosion inhibitors, biocides, and stimulants. Caffeine, paraxanthine, theobromine, tolyltriazole, 1H-benzotriazole, and atrazine were detected in>50% of all samples. The detection frequencies of carbamazepine, iopamidol, diuron, sulfamethoxazole, paracetamol, theophylline, and atenolol were between 20% and 32%. As caffeine is linked to untreated wastewater, the widespread occurrence of raw sewage in marine environments and thus potentially elevated nutrient concentrations and risk for the presence of wastewater-related pathogens is remarkable. PMID:25015017

  1. Recent Development of Eslicarbazepine Acetate, a New Drug against Epilepsy%治疗癫痫新药醋酸艾司利卡西平研究进展

    Institute of Scientific and Technical Information of China (English)

    饶志方; 王婉钢

    2015-01-01

    查阅国内外关于醋酸艾司利卡西平治疗癫痫的最新文献。文献结果表明,醋酸艾司利平口服吸收快、半衰期长、药物动力学呈线性,无明显的药物相互关系。与卡马西平、奥卡西平相比较,醋酸艾司利平治疗效果更加显著。%The latest literatures on eslicarbazepine acetate in the treatment of epilepsy from home and abroad were referred. The results showed that the oral absorption of eslicarbazepine acetate is quick with long half life, linear pharmacokinetics and low potential of drug-drug interactions. Compared with carbamazepine and oxcarbazepine, eslicarbazepine acetate is more effective against epilepsy.

  2. Comments on the Eslicarbazepine Acetate Section of the Article ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’

    Directory of Open Access Journals (Sweden)

    Patricio Soares-da-Silva

    2010-12-01

    Full Text Available The recent review of Matthew D. Krasowski on ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’ is a useful foundation of comparative interpretations on our current knowledge about therapeutic drug monitoring. Within the review, the statement that therapeutic drug monitoring has a minimal role in the therapeutic use of eslicarbazepine acetate due to its relatively predictable pharmacokinetics reflects the existing body of evidence although some information such as eslicarbazepine acetate’s chemical structure, proportions of its metabolites, their pharmacokinetics and chiral method of plasma level measurement need to be revised. These critical characteristics differentiate the novel compound from former dibenzazepines such as carbamazepine and oxcarbazepine in its clinical effects and needs for therapeutic drug monitoring.

  3. Comments on the Eslicarbazepine Acetate Section of the Article ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’

    Science.gov (United States)

    Öztiryaki, Ahmet H.; Soares-da-Silva, Patricio

    2010-01-01

    The recent review of Matthew D. Krasowski on ‘Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications’ is a useful foundation of comparative interpretations on our current knowledge about therapeutic drug monitoring. Within the review, the statement that therapeutic drug monitoring has a minimal role in the therapeutic use of eslicarbazepine acetate due to its relatively predictable pharmacokinetics reflects the existing body of evidence although some information such as eslicarbazepine acetate’s chemical structure, proportions of its metabolites, their pharmacokinetics and chiral method of plasma level measurement need to be revised. These critical characteristics differentiate the novel compound from former dibenzazepines such as carbamazepine and oxcarbazepine in its clinical effects and needs for therapeutic drug monitoring.

  4. Occurrence and fate of pharmaceutically active compounds in the environment, a case study: Hoeje River in Sweden

    International Nuclear Information System (INIS)

    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 β-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 β-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-) and boron

  5. 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.

  6. Refractory epilepsy accompanying acute encephalitis with multifocal cortical lesions: possible autoimmune etiology.

    Science.gov (United States)

    Okanishi, Tohru; Mori, Yuka; Kibe, Tetsuya; Takahashi, Yukitoshi; Saito, Yoshiaki; Maegaki, Yoshihiro; Yokochi, Kenji

    2007-10-01

    We report on a 14-year-old male suffering from acute encephalitis, whose clinical course met the criteria for acute encephalopathy with refractory, repetitive partial seizures (AERRPS). He presented with extremely refractory partial and secondary generalized seizures, and required high-dose barbiturate infusion therapy for 57 days under mechanical ventilation. Seven weeks after onset, the seizures were ameliorated by treatment with sodium bromide, carbamazepine, clobazam, and high-dose phenobarbital. Magnetic resonance imaging on day 14 of admission showed multifocal cortical lesions scattered in the bilateral hemispheres; these disappeared on day 34. Diffuse and mild atrophy of the cerebral cortex, and moderate atrophy of the hippocampus, appeared by day 61. Serum anti-glutamate receptor epsilon2 autoantibodies were detected on day 2. The patient was discharged after 113 days of admission with intractable epilepsy, memory disability, and regression of intelligence. We discuss the etiological significance of the multifocal lesions, which are unusual findings on neuroimaging of AERRPS. PMID:17442514

  7. Antimanic efficacy of retigabine in a proposed mouse model of bipolar disorder

    DEFF Research Database (Denmark)

    Nielsen, Ditte Dencker; Bak-Jensen, Henriette Husum

    2010-01-01

    and an increase in severity with time. Recurrence of episodes in bipolar disorders is suggested to reflect a process of sensitization. Repeated intermittent administration of amphetamine in rodents gives rise to a behavioral sensitization phenomena argued to have similarities to the sensitization found in humans....... The aims were therefore to explore the predictive validity of the amphetamine sensitization model as a behavioral model of mania by testing the effect of a range of antimanic drugs and to evaluate the effect of retigabine on the sensitized amphetamine response. Furthermore, since withdrawal from prolonged...... use of amphetamine in humans can result in depression symptoms it was explored if a state of anhedonia could be assessed by testing saccharine preference before and during the withdrawal period of the model. The tested antimanic drugs (lithium, valproate, carbamazepine and lamotrigine) all attenuated...

  8. 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.

  9. The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.

    Science.gov (United States)

    Bromley, R

    2016-09-01

    A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research. PMID:27312074

  10. 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%.

  11. 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.

  12. The effect of medication adherence on health care utilization in bipolar disorder.

    Science.gov (United States)

    Lew, Kim H; Chang, Eunice Y; Rajagopalan, Krithika; Knoth, Russell L

    2006-09-01

    A retrospective analysis of electronic prescription and medical claims representing approximately 1.4 million managed care commercial health plan members with mental health benefits was conducted. The effect of patient adherence to traditional mood-stabilizer therapy (lithium, valproate, carbamazepine, lamotrigine, or oxcarbazepine) for bipolar disorder on mental health-related hospitalization was assessed among 1,399 patients (mean age, 42.9 yr; 66.3% female) studied. Reduced adherence to traditional mood-stabilizing therapy (< 80%) in patients with bipolar disorder was associated with significantly greater risk of mental health-related, emergency room visits (odds ratio, 1.98; 95% confidence interval, 1.38-2.84) and inpatient hospitalizations (odds ratio, 1.71; 95% confidence interval, 1.27-2.32), even after adjusting for age, gender, and comorbidity. PMID:17017312

  13. Acesulfame-K and pharmaceuticals as co-tracers of municipal wastewater in a receiving river.

    Science.gov (United States)

    Liu, YingYing; Blowes, David W; Groza, Laura; Sabourin, Michelle J; Ptacek, Carol J

    2014-12-01

    Wastewater treatment plant (WWTP) effluents are important sources of emerging contaminants at environmentally-relevant concentrations. In this study, water samples were collected from a river downstream of two WWTPs to identify practical tracers for tracking wastewater. The results of the study indicate elevated concentrations of Cl(-), nutrients (NH3-N and NO2(-)), the artificial sweetener acesulfame-K (ACE-K), and the pharmaceuticals carbamazepine (CBZ), caffeine (CAF), sulfamethoxazole (SMX), ibuprofen (IBU), gemfibrozil (GEM), and naproxen (NAP) in the river close to the WWTPs that decreased with distance downstream. A correlation analysis using the Spearman Rank method showed that ACE-K, CBZ, GEM, NAP, and Cl(-) were strongly correlated with each other over a 31 km stretch of the river in the study area. The strong correlations of these target compounds indicate that the artificial sweetener ACE-K and the pharmaceuticals CBZ, GEM, and NAP can potentially be used as co-tracers to track wastewater. PMID:25359282

  14. 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

  15. MRI 3D CISS- A Novel Imaging Modality in Diagnosing Trigeminal Neuralgia - A Review.

    Science.gov (United States)

    Besta, Radhika; Shankar, Y Uday; Kumar, Ashwini; Rajasekhar, E; Prakash, S Bhanu

    2016-03-01

    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

  16. Spontaneous periodic hypothermia and hyperhidrosis.

    Science.gov (United States)

    Dundar, Nihal Olgac; Boz, Adil; Duman, Ozgur; Aydin, Funda; Haspolat, Senay

    2008-12-01

    We present a patient diagnosed with Shapiro syndrome without corpus callosum agenesis. A 4-year-old-girl was admitted to the hospital with complaints of sweating, cooling, and drowsiness that continued during the last week of her admission. Attacks occurred almost daily, and lasted for about 1 hour. All laboratory findings, as well as Holter and echocardiography results, were normal. Cranial magnetic resonance imaging demonstrated an intact corpus callosum, and electroencephalography obtained during an attack revealed normal findings. However, technetium 99m-labeled hexamethylpropylene amine oxime brain single-photon emission computed tomography indicated increased perfusion in the right thalamus, basal ganglia, and inferior frontal areas during a hypothermic period. Although oxcarbazepine reduced the frequency of attacks, they were not halted completely. The patient responded better to carbamazepine. PMID:19027594

  17. Irrigation of treated wastewater in Braunschweig, Germany

    DEFF Research Database (Denmark)

    Ternes, T.A.; Bonerz, M.; Herrmann, N.;

    2007-01-01

    of digested sludge, because many polar compounds do not sorb to sludge and lipophilic compounds are not mobile in the soil-aquifer. Most of the selected PPCPs were never detected in any of the lysimeter or groundwater samples, although they were present in the treated wastewater irrigated onto the fields...... of the sewage treatment plant (STP) of Braunschweig is used for irrigation, while during summer digested sludge is mixed with the effluent. In the present case study six wells and four lysimeters located in one of the irrigated agricultural fields were monitored with regard to the occurrence of 52....... In the groundwater and lysimeter samples primarily the ICM diatrizoate and iopamidol, the antiepileptic carbamazepine and the antibiotic sulfamethoxazole were detected up to several mu g l(-1), while the acidic pharmaceuticals, musk fragrances, estrogens and betablockers were likely sorbed or transformed while...

  18. Evaluation of pre-treatments for inhibiting bromate formation during ozonation

    DEFF Research Database (Denmark)

    Antoniou, Maria; Andersen, Henrik Rasmus

    2011-01-01

    limit of 10 μg/L. Depression of solution pH to 6.0, reduced BrO3- formation to half, but it was still well above the water limit. Pre-treatment with NH4+ also reduced BrO3- formation by approximately 50%, though it reduced atrazine degradation to 65%. Pre-treatment with Cl2/NH4+ reduced BrO3- formation......This study compared several pre-treatment methods for inhibiting BrO3- formation during ozonation of tap water, from the DTU campus, including H2O2 addition (perozone), pH-depression, NH4+ and Cl2/NH4+ addition. At the same time, the inhibition of atrazine and carbamazepine removal was evaluated...

  19. Flecainide-Responsive Myotonia Permanens With SNEL Onset: A New Case and Literature Review.

    Science.gov (United States)

    Portaro, Simona; Rodolico, Carmelo; Sinicropi, Stefano; Musumeci, Olimpia; Valenzise, Mariella; Toscano, Antonio

    2016-04-01

    Sodium channel myotonias are inherited muscle diseases linked to mutations in the voltage-gated sodium channel. These diseases may also affect newborns with variable symptoms. More recently, severe neonatal episodic laryngospasm (SNEL) has been described in a small number of patients. A timely diagnosis of SNEL is crucial because a specific treatment is now available that will likely reduced laryngospasm and improve vital and cerebral outcomes. We report here on an 8-year-old girl who had presented, at birth, with SNEL who subsequently developed myotonia permanens starting at age 3 years. Results of molecular analysis revealed a de novo SCN4A G1306E mutation. The girl was treated with carbamazepine, acetazolamide, and mexiletine, with little improvement; after switching her treatment to flecainide, she experienced a dramatic reduction in muscle stiffness and myotonic symptoms as well as an improvement in behavior. PMID:26944947

  20. 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.

  1. Treatment of anorexia nervosa with antidepressants.

    Science.gov (United States)

    Hudson, J I; Pope, H G; Jonas, J M; Yurgelun-Todd, D

    1985-02-01

    Nine patients with anorexia nervosa were treated with antidepressant medications from three classes: tricyclics, monoamine oxidase inhibitors, and triazolopyridines. A tenth patient was treated with the combination of lithium carbonate and carbamazepine. With either the initial or a subsequent medication trial, four patients had displayed significant improvement in weight and in other anorexic and bulimic symptoms. Three additional patients had a marked or moderate improvement in bulimic symptoms, one with moderate and two without any weight gain. Two other patients had moderate weight gain. Side effects were a significant problem in many of the patients. These preliminary results suggest that antidepressants may be of benefit in the treatment of some patients with anorexia nervosa. PMID:3919068

  2. 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.

  3. 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

  4. 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.

  5. Evaluation of acute effects of four pharmaceuticals and their mixtures on the copepod Tisbe battagliai.

    Science.gov (United States)

    Trombini, Chiara; Hampel, Miriam; Blasco, Julián

    2016-07-01

    The individual and combined toxicities of acetaminophen, carbamazepine, diclofenac and ibuprofen have been examined in neonate nauplii (medium)/PNEC (predicted no effect concentration) ratios. Results suggest that, at environmental concentrations, none of the compounds is harmful for the aquatic environment (low or no risk). Toxicity data obtained for mixtures were compared with predictions derived from three different models: Concentration Addition (CA), Independent Action (IA) and Combination Index (CI). The classical modeling approaches CA and IA failed to predict the observed mixture toxicity, thus indicating that single compound toxicity data are not sufficient to predict toxicity of drug mixtures on Tisbe species. However, the use of the CI seems to provide better predictions of pharmaceutical toxicity. PMID:27135693

  6. 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.

  7. 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.

  8. 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.

  9. Biotransformation of pharmaceuticals under nitrification, nitratation and heterotrophic conditions.

    Science.gov (United States)

    Fernandez-Fontaina, E; Gomes, I B; Aga, D S; Omil, F; Lema, J M; Carballa, M

    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. PMID:26479917

  10. Objective assessment of autonomic signs during triggered first division trigeminal neuralgia.

    Science.gov (United States)

    Pareja, J A; Barón, M; Gili, P; Yangüela, J; Caminero, A B; Dobato, J L; Barriga, F J; Vela, L; Sánchez-del-Río, M

    2002-05-01

    A total of 26 episodes of V-1 trigeminal neuralgia attacks have been recorded in two female patients. Autonomic phenomena were assessed according to a semiquantitative scale. Attacks lasted 17 +/- 5 s. Mild lacrimation without conjunctival hyperaemia, rhinorrhea or ptosis was observed, even in relatively long lasting episodes. This is in clear contradiction with SUNCT (shortlasting, unilateral, neuralgiform headache with conjunctival injection, tearing and rhinorrhea) attacks that are always dramatically accompanied by both lacrimation and conjunctival injection of the symptomatic side from the very onset of symptoms. Carbamazepine provided complete and sustained relief of symptoms in both patients. Herein we will show differential autonomic features of V-1 trigeminal neuralgia vs. SUNCT that will both aid the clinician to distinguish both syndromes and stress that both entities are nosologicaly different. PMID:12100085

  11. Plant uptake of pharmaceutical chemicals detected in recycled organic manure and reclaimed wastewater.

    Science.gov (United States)

    Tanoue, Rumi; Sato, Yuri; Motoyama, Miki; Nakagawa, Shuhei; Shinohara, Ryota; Nomiyama, Kei

    2012-10-17

    Land application of recycled manure produced from biosolids and reclaimed wastewater can transfer pharmaceutical chemicals to terrestrial environments, giving rise to potential accumulation of these residues in edible plants. In this study, the potential for plant uptake of 13 pharmaceutical chemicals, and the relation between the accumulation features within the plant and the physicochemical properties were examined by exposing pea and cucumber to an aqueous solution containing pharmaceutical chemicals. Ten of 13 compounds tested were detected in plant leaves and stems. Comparison of the plant uptake characteristics and the octanol-water partition coefficient of pharmaceutical chemicals showed that compounds with an intermediate polarity such as carbamazepine and crotamiton could be easily transported to plant shoots. Moreover, these results suggest the possibility of highly hydrophilic pharmaceutical chemicals such as trimethoprim and sulfonamides to be accumulated in plant roots owing to their low permeability in root cell membranes. PMID:23003104

  12. 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.

  13. 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

  14. 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.)

  15. 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.

  16. Prioritizing research for trace pollutants and emerging contaminants in the freshwater environment

    International Nuclear Information System (INIS)

    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, βE2, DEET, triclosan, acetaminophen, and E1) because they occur frequently in the freshwater environment and pose a human health hazard at

  17. Poison-Induced Seizures in 66 Patients: Causes, Treatments and Outcomes

    Directory of Open Access Journals (Sweden)

    F Gheshlaghi

    2008-06-01

    Full Text Available Background: Poisoning is one of the major causes of seizure in emergency medicine. Because of the varying availability of drugs in different areas and insufficient control of the sale of some dangerous industrial substances, the causes of seizure in poisoned patients may be differ in our society. In this study, we examine the causes of seizures in poisoned patients in Iran, and their outcomes.Methods: This retrospective and analytical-descriptive study investigated the sex, age, type of poison, presence and type of seizure, seizure treatment and outcome from the records of 2,220 hospitalized poison victims from 2001 to 2003 in poison emergency departments in Noor Hospital. Data was analyzed by one-way analysis of variance and chi square tests using SPSS.Results: Of the 2,220 patient records examined, 66 patients developed seizure. Seizure was more common in men (33 patients, and most common in the 15-40 year age group (28 patients. The most common causes of seizure were tricyclic antidepressants (TCA (39.7%, organophosphates (17.5%, carbamazepine (7.9% and organochlorines (6.3%. However, status epilepticus was more common in organochlorine (25%, organophosphate, TCA (18.75%, and carbamazepine (12.5% poisoning. There was a negative relationship between age and type of seizures. Seizure was not related to previous history of seizure. Midazolam alone (25% was the most effective drug for controlling seizures. Death occurred in six patients with or without renal complication. The mortality rate among poisoned patients with seizure was 37.5%.Conclusion: The incidence of seizure in our study reflects the availability of certain drugs and toxins that require more steadfast control. Midazolam, with its low side effects, may be the drug of choice for the treatment of status epilepticus in poisoning.

  18. 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).

  19. Gabapentin reverses central pain sensitization following a collagenase-induced intrathalamic hemorrhage in rats

    Directory of Open Access Journals (Sweden)

    Castel A

    2013-12-01

    Full Text Available Aude Castel, Pascal VachonFaculty of Veterinary Medicine, Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, QC, CanadaPurpose: The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP, amitriptyline (AMI, and carbamazepine (CARBA for the treatment of a rodent central neuropathic pain model.Methods: Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug.Results: A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05. AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant.Conclusion: Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA.Keywords: central pain, thalamus, amitriptyline, carbamazepine

  20. A national survey of trace organic contaminants in Australian rivers.

    Science.gov (United States)

    Scott, Philip D; Bartkow, Michael; Blockwell, Stephen J; Coleman, Heather M; Khan, Stuart J; Lim, Richard; McDonald, James A; Nice, Helen; Nugegoda, Dayanthi; Pettigrove, Vincent; Tremblay, Louis A; Warne, Michael St J; Leusch, Frederic D L

    2014-09-01

    Trace organic contaminant (TrOC) studies in Australia have, to date, focused on wastewater effluents, leaving a knowledge gap of their occurrence and risk in freshwater environments. This study measured 42 TrOCs including industrial compounds, pesticides, and pharmaceuticals and personal care products by liquid chromatography tandem mass spectrometry at 73 river sites across Australia quarterly for 1 yr. Trace organic contaminants were found in 92% of samples, with a median of three compounds detected per sample (maximum 18). The five most commonly detected TrOCs were the pharmaceuticals salicylic acid (82%, maximum = 1530 ng/L), paracetamol (also known as acetaminophen; 45%, maximum = 7150 ng/L), and carbamazepine (27%, maximum = 682 ng/L), caffeine (65%, maximum = 3770 ng/L), and the flame retardant (2-chloroethyl) phosphate (44%, maximum = 184 ng/L). Pesticides were detected in 28% of the samples. To determine the risk posed by the detected TrOCs to the aquatic environment, hazard quotients were calculated by dividing the maximum concentration detected for each compound by the predicted no-effect concentrations. Three of the 42 compounds monitored (the pharmaceuticals carbamazepine and sulfamethoxazole and the herbicide simazine) had a hazard quotient >1, suggesting that they may be causing adverse effects at the most polluted sites. A further 10 compounds had hazard quotients >0.1, indicating a potential risk; these included four pharmaceuticals, three personal care products, and three pesticides. Most compounds had hazard quotients significantly <0.1. The number of TrOCs measured in this study was limited and further investigations are required to fully assess the risk posed by complex mixtures of TrOCs on exposed biota. PMID:25603256

  1. 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.

  2. LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Demétrio Frederico N

    2010-06-01

    Full Text Available Abstract Background The challenge of Bipolar Disorder (BD treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of LIthium and CArbamazepine compared to lithium and VALproic acid in the treatment of young bipolar patients study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs. Methods LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine. Patients will be followed up for 8 weeks in phase I (acute treatment, 6 months in phase II (continuation treatment and 12 months in phase III (maintenance treatment. Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study. Results LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012. Conclusions Trials comparing specific treatments efficacy in BD (head to head can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease. Trial registration ClinicalTrials.gov Identifier: NCT00976794

  3. P-glycoprotein alters blood–brain barrier penetration of antiepileptic drugs in rats with medically intractable epilepsy

    Directory of Open Access Journals (Sweden)

    Ma A

    2013-12-01

    Full Text Available Aimei Ma,1,* Cuicui Wang,2,3,* Yinghui Chen,2,3 Weien Yuan4 1Department of Neurology, The People's Hospital of Shanxi Province, Taiyuan, 2Department of Neurology, Jinshan Hospital, Fudan University, 3Department of Neurology, Shanghai Medical College, Shanghai, 4School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: P-glycoprotein is one of the earliest known multidrug transporters and plays an important role in resistance to chemotherapeutic drugs. In this study, we detected levels of P-glycoprotein and its mRNA expression in a rat brain model of medically intractable epilepsy established by amygdala kindling and drug selection. We investigated whether inhibition of P-glycoprotein affects the concentration of antiepileptic drugs in cortical extracellular fluid. We found that levels of P-glycoprotein and its mRNA expression were upregulated in epileptic cerebral tissue compared with cerebral tissue from normal rats. The concentrations of two antiepileptic drugs, carbamazepine and phenytoin, were very low in the cortical extracellular fluid of rats with medically intractable epilepsy, and were restored after blockade of P-glycoprotein by verapamil. These results show that increased P-glycoprotein levels alter the ability of carbamazepine and phenytoin to penetrate the blood–brain barrier and reduce the concentrations of these agents in extracellular cortical fluid. High P-glycoprotein levels may be involved in resistance to antiepileptic drugs in medically intractable epilepsy. Keywords: P-glycoprotein, medically intractable epilepsy, antiepileptic drugs, amygdala kindling, verapamil

  4. [Drug induced eosinophilic pleural effusion].

    Science.gov (United States)

    Vasilescu, Raluca

    2014-01-01

    The hypersensitivity reactions induced by drugs, some widely used, like central nervous system medication, can have various presentations. The lung is a frequent target for such events. We present the case of 40-year-old male patient, non-smoker, with infant encephalopaty, seizures since age of 6 with polimorphic crisis (mainly absences), with anticonvulsivant treatment since 2011 (carbamazepine, sodium valproate, levetiracetam), with no respiratory medical history. Current symptoms started two weeks before, with chest pain, dry cough. He received no antibiotics. Chest X-ray and thoracic CT scan (27 June 2013) showed a left pleral effusion. Left exploratory thoracocentesis extracted 20 ml reddish pleural fluid: eosinophilic exsudate (60%) with normal adenosin deaminase. He also presents moderate blood eosinophilia (13.7%-1780/mm3). Pulmonary infarction with secondary pleurisy, thoracic trauma, acute pancreatitis with secondary pleurisy were excluded. No Loeffler transient infiltrates were documented, serology for Toxocara is IgG positive (historical) and not significant for current episode, no symptoms suggestive for toxocarosis (characteristic to young children, patient had no liver enlargement etc.), no hidatidosis or trichinelosis were found. As an exclusion diagnosis, a hypersensitivity reaction to anticonvulsivant medication was considered (mentioned in literature) carbamazepine and sodium valproate (even if medication was taken for a longer time), with blood and pleural eosinophilia. Together with the neurologist, the mentioned drugs were stopped and he was started on lamotrigine 2 tb/day and levetiracetam 1 tb/day, well tolerated, no absences were noticed. Total remission of blood eosinophilia and partial remission of pleural effusion were noticed. Subsequent follow-ups confirm favourable evolution, with healing of pleurisy and normal blood cell count, which are stable at 7 months after changing anticonvulsivant treatment. PMID:25241560

  5. 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. PMID:23973619

  6. 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. PMID:25042244

  7. Super-fine powdered activated carbon (SPAC) for efficient removal of micropollutants from wastewater treatment plant effluent.

    Science.gov (United States)

    Bonvin, Florence; Jost, Livia; Randin, Lea; Bonvin, Emmanuel; Kohn, Tamar

    2016-03-01

    In an effort to mitigate the discharge of micropollutants to surface waters, adsorption of micropollutants onto powdered activated carbon (PAC) after conventional wastewater treatment has been identified as a promising technology for enhanced removal of pharmaceuticals and pesticides from wastewater. We investigated the effectiveness of super-fine powdered activated carbon, SPAC, (ca. 1 μm mean particle diameter) in comparison to regular-sized PAC (17-37 μm mean diameter) for the optimization of micropollutant removal from wastewater. Adsorption isotherms and batch kinetic experiments were performed for 10 representative micropollutants (bezafibrate, benzotriazole, carbamazepine, diclofenac, gabapentin, mecoprop, metoprolol, ofloxacin, sulfamethoxazole and trimethoprim) onto three commercial PACs and their super-fine variants in carbonate buffer and in wastewater effluent. SPAC showed substantially faster adsorption kinetics of all micropollutants than conventional PAC, regardless of the micropollutant adsorption affinity and the solution matrix. The total adsorptive capacities of SPAC were similar to those of PAC for two of the three tested carbon materials, in all tested waters. However, in effluent wastewater, the presence of effluent organic matter adversely affected micropollutant removal, resulting in lower removal efficiencies especially for micropollutants with low affinity for adsorbent particles in comparison to pure water. In comparison to PAC, SPAC application resulted in up to two-fold enhanced dissolved organic carbon (DOC) removal from effluent wastewater. The more efficient adsorption process using SPAC translates into a reduction of contact time and contact tank size as well as reduced carbon dosing for a targeted micropollutant removal. In the tested effluent wastewater (5 mg/L DOC), the necessary dose to achieve 80% average removal of indicator micropollutants (benzotriazole, diclofenac, carbamazepine, mecoprop and sulfamethoxazole) ranged

  8. Removal of persistent pharmaceutical micropollutants from sewage by addition of PAC in a sequential membrane bioreactor.

    Science.gov (United States)

    Serrano, D; Suárez, S; Lema, J M; Omil, F

    2011-10-15

    The performance of a membrane bioreactor operating in a sequential mode (SMBR) using an external flat-plate membrane was investigated. After 200 days of operation, a single addition of 1 g L(-1) Powdered Activated Carbon (PAC) was added directly into the mixed liquor in order to enhance the simultaneous removal of nutrients and pharmaceutical micropollutants from synthetic urban wastewater. Throughout the entire operation (288 days), Chemical Oxygen Demand (COD) removal efficiencies were up to 95%, ammonium nitrogen removal was maintained over 70-80%, whereas phosphorus removal achieved only high values (around 80%) after PAC addition. During the operation of the SMBR without PAC addition, micropollutants which exerted a more recalcitrant behaviour were carbamazepine, diazepam, diclofenac and trimethoprim, with no significant removal. On the other hand, moderate removals (42-64%) were observed for naproxen and erythromycin, whereas ibuprofen, roxithromycin and fluoxetine were removed in the range of 71-97%. The addition of PAC into the aeration tank was a successful tool to improve the removal of the more recalcitrant compounds up to 85%. The highest removal with PAC was observed for carbamazepine, trimethoprim as well as for roxithromycin, erythromycin and fluoxetine. The latter four compounds have amine groups and pKa in the range 6.7-10.1, thus the interaction between PAC and the positively charged amino groups might be the cause of their comparatively better results. Microbial ecology present in the biomass showed a higher abundance of Accumulibacter phosphatis as well as the ammonium oxidizing bacteria belonging to the genus Nitrosomonas after PAC addition. PMID:21864878

  9. 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. PMID:27049789

  10. The associations between idiosyncratic adverse drug reactions and HLA alleles and their underlying mechanism%遗传异质性药物毒副作用与HLA基因关联及分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    王青; 梅虎; 张亚兰; 潘显超; 谭文; 晁丽

    2013-01-01

    随着高通量基因测序技术的发展,全基因组关联分析(genome-wide association study,GWAS)被越来越多地应用到遗传异质性药物毒副作用(adverse drug reactions,ADRs)研究中.越来越多的研究发现:遗传异质性ADRs与人类白细胞抗原(human leukocyte antigen,HLA)密切相关,如阿巴卡韦(abacavir)与HLA-B*5701、别嘌醇(allopurinol)与HLA-B*5801、卡马西平(carbamazepine)与HLA-B*1502等基因关联.针对上述基因关联现象,相继提出半抗原理论、危险因子理论、“P-I”理论以及最新提出的自身免疫机制.本文就遗传异质性ADRs与HLA基因关联及其机制研究的最新进展进行了详细综述.%With the advent of Twenty-First century,more and more genome-wide association studies (GWAS)showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles,such as the associations of abacavir-HLA-B*5701,allopurinol-HLA-B*5801,and carbamazepineHLA-B*1502,etc.To explore the mechanisms of these idiosyncratic drug reactions,hapten hypothesis,danger signal hypothesis,pharmacological interaction (P-I) concept and autoimmune mechanism are proposed.In this paper,recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

  11. 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

  12. 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.

  13. 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.

  14. Fate of pharmaceuticals in rivers: Deriving a benchmark dataset at favorable attenuation conditions.

    Science.gov (United States)

    Kunkel, Uwe; Radke, Michael

    2012-11-01

    Pharmaceutical residues are commonly detected organic micropollutants in the aquatic environment. Their actual fate in rivers is still incompletely understood as their elimination is highly substance specific and studies often report contradictory results. To elucidate the ceiling of attenuation rates of pharmaceuticals in rivers we carried out a study at a river with favorable conditions for the elimination of organic micropollutants. Experiments were carried out at a small stream in Germany. Composite samples were taken at both ends of a 12.5 km long river stretch located downstream of a sewage treatment plant and analyzed for 10 pharmaceuticals. Moreover, pore water samples were taken and in situ photolysis experiments at several sites within the river stretch were performed to assess the importance of these individual elimination mechanisms. Pharmaceutical concentration in the surface water at the first sampling site ranged from 3.5 ng L(-1) for propranolol to 1400 ng L(-1) for diclofenac. In comparison to carbamazepine which was used as persistent tracer, all other pharmaceuticals were attenuated along the river stretch. Their elimination was higher in a sunny, dry weather period (period I) compared to a period with elevated discharge after a heavy rainfall (period II). Overall, the measured elimination rates ranged from 25% for sulfamethoxazole (period II) to 70% for propranolol (period I). Photolysis was only a relevant elimination process for diclofenac and potentially also for sotalol; for these compounds phototransformation half-life times of some hours were determined in the unshaded parts of the river. Biotransformation in the sediments was also an important attenuation process since the concentrations of the other pharmaceuticals in the sediments decreased relative to carbamazepine with depth. For the chiral betablocker metoprolol this biotransformation was also confirmed by a decrease in the enantiomer fractionation from 0.49 at site A to 0.43 at

  15. Pharmaceuticals and organic pollution mitigation in reclamation osmosis brines by UV/H2O2 and ozone.

    Science.gov (United States)

    Justo, A; González, O; Aceña, J; Pérez, S; Barceló, D; Sans, C; Esplugas, S

    2013-12-15

    One significant disadvantage of using reverse osmosis (RO) for reclamation purposes is the need to dispose of the RO retentates. These retentates contain a high concentration of micropollutants, effluent organic matter (EfOM) and other inorganic constituents, which are recalcitrant to biological treatment and may impact the environment. The occurrence of 11 pharmaceuticals (concentrations ranging from 0.2 to 1.6 μg L(-1)) and their mitigation in RO retentates by a UV/H2O2 process and ozonation was studied using a wide range of oxidant dosages. Eleven pharmaceuticals were identified at. Initial observed kinetic constants (kobs) were calculated for the different pharmaceuticals. Other typical wastewater parameters were also monitored during the UV/H2O2 and ozonation reactions. The range for kobs was found to be 0.8-12.8L mmol O3(-1) and 9.7-29.9 L mmol H2O2(-1) for the ozonation and UV/H2O2 process, respectively. For ozonation, Atenolol, Carbamazepine, Codeine, Trimethoprim and Diclofenac showed the lowest initial kobs (in the order mentioned). Atenolol and Carbamazepine appeared as the most ozone resistant pharmaceuticals, exhibiting the lowest percentage of elimination at low ozone doses. On the other hand, despite the non-selectivity of HO, differences in the initial kobs were also observed during the UV/H2O2 process. Trimethoprim, Paroxetine and Sulfamethoxazole exhibited the lowest initial kobs values (in the order mentioned). Trimethoprim and Paroxetine also exhibited the lowest percentage removal when low H2O2 doses were assayed. The compounds that were identified as problematic during ozonation were more efficiently removed by the UV/H2O2 process. UV/H2O2 generally appeared to be a more efficient technology for removing pharmaceuticals from RO brines compared to ozonation. PMID:23768786

  16. Quantification of emerging micropollutants in an amphipod crustacean by nanoliquid chromatography coupled to mass spectrometry using multiple reaction monitoring cubed mode.

    Science.gov (United States)

    Sordet, Martin; Berlioz-Barbier, Alexandra; Buleté, Audrey; Garric, Jeanne; Vulliet, Emmanuelle

    2016-07-22

    An innovative analytical method has been developed to quantify the bioaccumulation in an amphipod crustacean (Gammarus fossarum) of three micropollutants regarded as anthropic-pollution markers: carbamazepine, oxazepam, and testosterone. A liquid-liquid extraction assisted by salts, known as QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) was miniaturised and optimised, so it could be adapted to the low mass samples (approximatively 5mg dry weight). For this same reason and in order to obtain good sensitivity, ultra-trace analyses were carried out by means of nanoliquid chromatography. A preconcentration system by on-column trapping was optimised to increase the injection volume. In order to improve both sensitivity and selectivity, the multiple reaction monitoring cubed mode analyses (MRM(3)) were carried out, validated and compared to the classic MRM. To the best of our knowledge, this is the first time that MRM(3) is coupled to nanoliquid chromatography for the analysis and detection of organic micropollutants <300Da. The optimised extraction method exhibited recoveries superior to 80%. The limits of quantification of the target compounds were 0.3, 0.7 and 4.7ng/g (wet weight) for oxazepam, carbamazepine and testosterone, respectively and the limits of detection were 0.1, 0.3 and 2.2ng/g (wet weight), respectively. The intra- and inter-day precisions were inferior to 7.7% and 10.9%, respectively, for the three levels of concentration tested. The analytical strategy developed allowed to obtain limits of quantification lower than 1ng/g (wet weight) and to establish the kinetic bioconcentration of contaminants within G. fossarum. PMID:27324621

  17. The effects of eslicarbazepine on persistent Na⁺ current and the role of the Na⁺ channel β subunits.

    Science.gov (United States)

    Doeser, Anna; Soares-da-Silva, Patricio; Beck, Heinz; Uebachs, Mischa

    2014-02-01

    Eslicarbazepine is the major active metabolite of eslicarbazepine acetate, a once-daily antiepileptic drug approved in Europe as adjunctive therapy for refractory partial-onset seizures in adults. This study was aimed to determine the effects of eslicarbazepine on persistent Na(+) currents (INaP) and the role of β subunits in modulating these effects. To study the role of β subunits of the Na(+) channel we used a mouse line genetically lacking either the β1 or β2 subunit, encoded by the SCN1B or SCN2B gene, respectively. Whole cell patch-clamp recordings were performed on CA1 neurons in hippocampal slices under control conditions and application of 300 μM eslicarbazepine. We examined INaP in acutely isolated CA1 neurons and repetitive firing in hippocampal slices of mice lacking β subunits and corresponding wild-type littermates. We found that eslicarbazepine caused a significant reduction of maximal INaP conductance and an efficient reduction of the firing rate in wild-type mice. We have shown previously a paradoxical increase of conductance of INaP caused by carbamazepine in mice lacking β1 subunits in the subthreshold range, leading to a failure in affecting neuronal firing (Uebachs et al., 2010). In contrast, eslicarbazepine did not cause this paradoxical effect on INaP in SCN1B null mice. Consequently, the effects of eslicarbazepine on repetitive firing were maintained in these animals. These results indicate that eslicarbazepine exerts effects on INaP similar to those known for carbamazepine. However, in animals lacking the β1 Na(+) channel subunit these effects are maintained. Therefore, eslicarbazepine potentially overcomes a previously described putative mechanism of resistance to established Na(+) channel acting antiepileptic drugs. PMID:24368131

  18. Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs.

    Science.gov (United States)

    Zaccara, Gaetano; Perucca, Emilio

    2014-12-01

    Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P-glycoprotein) and can reduce the efficacy of co-administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of

  19. Surface characterisation and photocatalytic performance of N-doped TiO2 thin films deposited onto 200 nm pore size alumina membranes by sol–gel methods

    International Nuclear Information System (INIS)

    Membrane filtration is employed for water treatment and wastewater reclamation purposes, but membranes alone are unable to remove pollutant molecules and certain pathogens. Photocatalytically active N-doped TiO2 coatings have been deposited by sol–gel onto 200 nm pore size alumina membranes for water treatment applications using two different methods, via pipette droplets or spiral bar applicator. The uncoated and coated membranes were characterised by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X-ray spectrometry (EDX). Both coatings showed the presence of N-doped anatase, with a surface coverage between 84 and 92%, and nitrogen concentration (predominantly interstitial) of 0.9 at.%. The spiral bar applicator deposited coatings exhibit a thicker mud-cracked surface layer with limited penetration of the porous membrane, whilst the pipette deposited coatings have mostly penetrated into the bulk of the membrane and a thinner layer is present at the surface. The photocatalytic activity (PCA), measured through the degradation of carbamazepine (CBZ), under irradiation of a solar simulator was 58.6% for the pipette coating and 63.3% for the spiral bar coating. These photocatalytically active N-doped sol–gel coated membranes offer strong potential in forming the fundamental basis of a sunlight based water treatment system. - Highlights: • Sol gel N-doped TiO2 thin films were deposited on 200 nm pore size Al2O3 membranes. • Two sol–gel methods have been compared – pipette drop and spiral bar deposition. • The coatings showed a similar microstructure and composition but different morphology. • The PCA (degradation of carbamazepine) was ∼60% for both sol–gel coatings. • The coated membranes are promising for use in a membrane based water treatment system

  20. The diagnosis and treatment of epilepsia partialis continua(a report of 3 cases)%部分性癫痫间持续状态的诊治(附3例病例随访研究)

    Institute of Scientific and Technical Information of China (English)

    刘永红; 李力; 李小宁; 邓艳春; 黄远桂

    2013-01-01

    Objective To discuss the diagnosis and treatment of epilepsia partialis continua (EPC). Methods We presented the case description of 3 patients diagnosed as epilepsia partialis continua. Results Topiramate or carbamazepine is effective to the patients with EPC. Conclusions The video-EEG, epileptic seizure formerly, seizure in the sleep, and interictal epileptic discharge are helpful to diagnose EPC. Oral topiramate or carbamazepine may be an effective therapeutic option on EPC.%目的 探讨部分性癫痫间持续状态的诊断和治疗.方法 对本院癫痫间中心收治的3例部分性癫痫间持续状态的诊断和抗癫痫间药物的选择进行分析.结果 托吡酯、卡马西平对于部分性癫痫间持续状态疗效显著.结论 部分性癫痫间持续状态的诊断及鉴别诊断不仅依靠发作期的视频脑电监测,其他因素诸如以往确定的癫痫 间发作、睡眠中发作、发作间期痫间样放电等同样重要.部分性癫痫间持续状态的治疗要注意用药的风险和疗效平衡.口服抗癫痫间药物的合理选择可以完全控制部分性癫痫 间持续状态.

  1. Electrochemical Transformation of Trace Organic Contaminants in Latrine Wastewater.

    Science.gov (United States)

    Jasper, Justin T; Shafaat, Oliver S; Hoffmann, Michael R

    2016-09-20

    Solar-powered electrochemical systems have shown promise for onsite wastewater treatment in regions where basic infrastructure for conventional wastewater treatment is not available. To assess the applicability of these systems for trace organic contaminant treatment, test compound electrolysis rate constants were measured in authentic latrine wastewater using mixed-metal oxide anodes coupled with stainless steel cathodes. Complete removal of ranitidine and cimetidine was achieved within 30 min of electrolysis at an applied potential of 3.5 V (0.7 A L(-1)). Removal of acetaminophen, ciprofloxacin, trimethoprim, propranolol, and carbamazepine (>80%) was achieved within 3 h of electrolysis. Oxidation of ranitidine, cimetidine, and ciprofloxacin was primarily attributed to reaction with NH2Cl. Transformation of trimethoprim, propranolol, and carbamazepine was attributed to direct electron transfer and to reactions with surface-bound reactive chlorine species. Relative contributions of aqueous phase ·OH, ·Cl, ·Cl2(-), HOCl/OCl(-), and Cl2 were determined to be negligible based on measured second-order reaction rate constants, probe compound reaction rates, and experiments in buffered Cl(-) solutions. Electrical energy per order of removal (EEO) increased with increasing applied potentials and current densities. Test compound removal was most efficient at elevated Cl(-) concentrations present when treated wastewater is recycled for use as flushing water (i.e., ∼ 75 mM Cl(-); EEO = 0.2-6.9 kWh log(-1) m(-3)). Identified halogenated and oxygenated electrolysis products typically underwent further transformations to unidentifiable products within the 3 h treatment cycle. Identifiable halogenated byproduct formation and accumulation was minimized during electrolysis of wastewater containing 75 mM Cl(-). PMID:27564843

  2. Medical treatment of nystagmus and ocular motor disorders.

    Science.gov (United States)

    Carlow, T J

    1986-01-01

    An increased compendium of drugs useful in ocular motor system dysfunction has expanded our capacity to treat selected ocular motility disorders. Adjunctive therapeutic modes (e.g., Fresnel prisms and orthoptic exercises) can also be beneficial. PAN and see-saw nystagmus can be treated with baclofen. Downbeat nystagmus may respond to clonazepam therapy, and prisms may help if the nystagmus can be modified with convergence. Congenital nystagmus may respond minimally to drugs (e.g., baclofen), but prisms or surgical procedures, or both, are still the primary treatment modalities. Innovar may be helpful in patients with severe, incapacitating vestibular disorders, and scopolamine alone or in combination with promethazine may be beneficial in patients with milder ambulatory acute peripheral vestibular disorders. Benign positional vertigo is best treated initially with positional exercises before drug therapy is instituted. Opsoclonus and ocular flutter have been treated successfully with corticosteroids, propranolol, and clonazepam, while microflutter, an extremely rare disorder, can resolve with baclofen. Although therapy with carbamazepine, 5-hydroxtryptophan, and scopolamine has been useful in selected patients with ocular palatal myoclonus, most do not respond to drug treatment. It is not usually necessary to treat voluntary nystagmus, but Fresnel prism lenses should be remembered in refractory patients. Potentially reversible and pseudointernuclear ophthalmoplegias also were discussed. Orthoptic exercises can be beneficial in posttraumatic internuclear ophthalmoplegia. Selected supranuclear palsies can be improved completely with the proper drug regimen. Lastly, superior oblique myokymia can be treated successfully with carbamazepine, with tight surveillance for possible adverse side effects. Descriptive phenomenology and pathophysiological localization must be correlated with brain stem neurochemistry and neuropharmacology to medically treat additional ocular

  3. High-content screening identifies a role for Na(+) channels in insulin production.

    Science.gov (United States)

    Szabat, Marta; Modi, Honey; Ramracheya, Reshma; Girbinger, Vroni; Chan, Forson; Lee, Jason T C; Piske, Micah; Kamal, Sepehr; Carol Yang, Yu Hsuan; Welling, Andrea; Rorsman, Patrik; Johnson, James D

    2015-12-01

    Insulin production is the central feature of functionally mature and differentiated pancreatic β-cells. Reduced insulin transcription and dedifferentiation have been implicated in type 2 diabetes, making drugs that could reverse these processes potentially useful. We have previously established ratiometric live-cell imaging tools to identify factors that increase insulin promoter activity and promote β-cell differentiation. Here, we present a single vector imaging tool with eGFP and mRFP, driven by the Pdx1 and Ins1 promoters, respectively, targeted to the nucleus to enhance identification of individual cells in a high-throughput manner. Using this new approach, we screened 1120 off-patent drugs for factors that regulate Ins1 and Pdx1 promoter activity in MIN6 β-cells. We identified a number of compounds that positively modulate Ins1 promoter activity, including several drugs known to modulate ion channels. Carbamazepine was selected for extended follow-up, as our previous screen also identified this use-dependent sodium channel inhibitor as a positive modulator of β-cell survival. Indeed, carbamazepine increased Ins1 and Ins2 mRNA in primary mouse islets at lower doses than were required to protect β-cells. We validated the role of sodium channels in insulin production by examining Nav1.7 (Scn9a) knockout mice and remarkably islets from these animals had dramatically elevated insulin content relative to wild-type controls. Collectively, our experiments provide a starting point for additional studies aimed to identify drugs and molecular pathways that control insulin production and β-cell differentiation status. In particular, our unbiased screen identified a novel role for a β-cell sodium channel gene in insulin production. PMID:27019722

  4. 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.

  5. 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.

  6. Physical growth and psychomotor development of infants exposed to antiepileptic drugs in utero

    Directory of Open Access Journals (Sweden)

    Arulmozhi T

    2006-01-01

    Full Text Available Objective: To evaluates the physical growth and psychomotor development of infants born to women with epilepsy on regular Anti Epileptic Drugs (AEDs. Setting: Govt. Stanley Medical College and Hospital, Tertiary care referral centre, Chennai. Design: Open prospective cohort study with a control group. Materials and Methods: Consecutive women with epilepsy who were on regular anticonvulsants were followed up from their first trimester. Their babies were examined at birth and anthropometric measurements including anterior fontanelle size were noted. They were followed up till one year and periodically evaluated at 1st, 6th and 12th month of age. Development testing using Griffith scale was done at 2nd, 6th and 12th month. An equal number of control babies were also studied using the same scale for one year at the specified intervals. The results in both the groups were compared. Results : 30 babies were enrolled in the case and control group. The AEDs received by the mothers with epilepsy were Phenytoin, Carbamazepine, and Sodium valproate. At birth and 1st month the weight, head circumference and length of case and control babies were equal. At 6th and 12th month reduction in the above 3 parameters were noted in the case babies ( P P P P monotherapy had a negative impact on sitting progression. Conclusion : Among infants exposed to AEDs in utero physical growth was equal to that of control at birth but reduced at 6th and 12th month probably due to extraneous factors. The Locomotor scores showed reduction in all areas in 2nd, 6th and 12th month except prone progression which alone improved by 12th month. Phenytoin exposure in utero resulted in large AF and it had a negative impact on sitting progression in comparison with Carbamazepine and Sodium valproate.

  7. 神经性肌强直5例报告并文献复习%Cases report and literature review of isaacs' syndrome

    Institute of Scientific and Technical Information of China (English)

    俞英欣; 刘志国; 戚晓昆

    2013-01-01

    Objective To evaluate clinical manifestation, characteristic electromyography and prognosis of Isaacs' syndrome. Methods Clinical data,characteristic electromyography,diagnosis and treatment of five cases with Isaacs' syndrome were analyzed retrospectively while making a literature review. Results Five cases' clinical manifestation were myok-ymia and hyperhidrosis. Electromyography show typical bigeminy, trigeminy and multigeminy motor unit discharge. Carbamaz-epine could relieve most of clinical symptoms. Conclusion Isaacs' syndrome is a rare peripheral nerves disease. The spontaneous and consecutive musculation is main clinical manifestation. Electromyography show typical bigeminy,trigeminy and multigeminy motor unit discharge. Carbamazepine is preferred drugs for Isaacs' syndrome. Regular following-up is necessary.%目的 探讨Isaacs综合征临床表现、肌电图特点及临床转归.方法 分析5例神经性肌强直病例的临床症候、肌电图表现、诊断及治疗情况,并进行文献回顾.结果 5例病例临床主要表现为肌肉颤搐、多汗等;肌电图表现为持续快速的二联、三联或多联的运动单位放电活动;应用卡马西平可缓解临床症状.结论 神经性肌强直是一种少见的周围神经病变,白发性连续性肌肉活动为其主要表现;肌电图特点为持续快速的二联、三联或多联运动单位放点活动;应用卡马西平治疗有效,但仍需定期随访.

  8. Attenuation of pharmaceuticals and their transformation products in a wastewater treatment plant and its receiving river ecosystem.

    Science.gov (United States)

    Aymerich, I; Acuña, V; Barceló, D; García, M J; Petrovic, M; Poch, M; Rodriguez-Mozaz, S; Rodríguez-Roda, I; Sabater, S; von Schiller, D; Corominas, Ll

    2016-09-01

    Pharmaceuticals are designed to improve human and animal health, but may also be a threat to freshwater ecosystems, particularly after receiving urban or wastewater treatment plant (WWTP) effluents. Knowledge on the fate and attenuation of pharmaceuticals in engineered and natural ecosystems is rather fragmented, and comparable methods are needed to facilitate the comprehension of those processes amongst systems. In this study the dynamics of 8 pharmaceuticals (acetaminophen, sulfapyridine, sulfamethoxazole, carbamazepine, venlafaxine, ibuprofen, diclofenac, diazepam) and 11 of their transformation products were investigated in a WWTP and the associated receiving river ecosystem. During 3 days, concentrations of these compounds were quantified at the influents, effluents, and wastage of the WWTP, and at different distances downstream the effluent at the river. Attenuation (net balance between removal and release from and to the water column) was estimated in both engineered and natural systems using a comparable model-based approach by considering different uncertainty sources (e.g. chemical analysis, sampling, and flow measurements). Results showed that pharmaceuticals load reduction was higher in the WWTP, but attenuation efficiencies (as half-life times) were higher in the river. In particular, the load of only 5 out of the 19 pharmaceuticals was reduced by more than 90% at the WWTP, while the rest were only partially or non-attenuated (or released) and discharged into the receiving river. At the river, only the load of ibuprofen was reduced by more than 50% (out of the 6 parent compounds present in the river), while partial and non-attenuation (or release) was observed for some of their transformation products. Linkages in the routing of some pharmaceuticals (venlafaxine, carbamazepine, ibuprofen and diclofenac) and their corresponding transformation products were also identified at both WWTP and river. Finally, the followed procedure showed that dynamic

  9. 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

  10. SERUM ANTIOXIDANT PARAMETERS IN PATIENTS POISONED BY DIFFERENT XENOBIOTICS.

    Science.gov (United States)

    Hydzik, Piotr; Krośniak, Mirosław; Francik, Renata; Gomółka, Ewa; Ebru, Ebru Derici; Zagrodzki, Paweł

    2016-01-01

    There is a great diversity of the acute drugs overdose cases in clinical toxicology. Clinical situation is complicated by the coexistence of factors predisposing to the development of adverse drug reactions (chronic use of drugs, polypharmacy, alcohol or drugs dependence, nutritional disorders) and by the presence of chronic organ damage, especially the liver and the kidney. The aim of this study was to evaluate whether there are sensitive plasma markers belonging to the antioxidant system in patients exposed to various xenobiotics. We measured the activity of antioxidant parameters: catalase (CAT), glutathione peroxidase (GPX3), glutathione (GSH), sulfhydryl groups (-SH), carbonyl groups (=CO) and free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH, assay) in serum of 49 patients with acute intoxication caused by carbamazepine (CBZ, n = 9), mixed drug intoxication (MDI) (n = 9), alcohol withdrawal syndrome (AWS, n = 9), acetaminophen (APAP, n = 7), tricyclic antidepressants (TCAs) (n = 5), valproic acids (VA, n = 4), narcotics (N, n = 3), and three others (benzodiazepines, BZD, n = 2; barbiturates, n = 1). The results were compared with the parameters of not intoxicated patients (n = 39). All patients had lower catalase activity in comparison to the control group (41.9 ± 16.5 vs. 196.0 ± 82.2 U/mg protein, p = 0.000), while the increase of GSH level was particularly apparent only in patients with AWS (391.3 ± 257.9 μmol/mg protein) compared to the control group (171.4 ± 88.4 μmol/mg protein, p = 0.034) and to patients intoxicated with carbamazepine (152.8 ± 102.5 μmol/mg protein, p = 0.027). Some differences, but without statistical significance, were also observed in GPX3 activity between different groups of poisoned patients. PMID:27180426

  11. 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.

  12. Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs.

    Science.gov (United States)

    Desaphy, Jean-François; Carbonara, Roberta; Costanza, Teresa; Conte Camerino, Diana

    2014-05-01

    Although the sodium channel blocker mexiletine is considered the first-line drug in myotonia, some patients experiment adverse effects, while others do not gain any benefit. Other antimyotonic drugs are thus needed to offer mexiletine alternatives. In the present study, we used a previously-validated rat model of myotonia congenita to compare six marketed sodium channel blockers to mexiletine. Myotonia was induced in the rat by injection of anthracen-9-carboxylic acid, a muscle chloride channel blocker. The drugs were given orally and myotonia was evaluated by measuring the time of righting reflex. The drugs were also tested on sodium currents recorded in a cell line transfected with the human skeletal muscle sodium channel hNav1.4 using patch-clamp technique. In vivo, carbamazepine and propafenone showed antimyotonic activity at doses similar to mexiletine (ED50 close to 5mg/kg); flecainide and orphenadrine showed greater potency (ED50 near 1mg/kg); lubeluzole and riluzole were the more potent (ED50 near 0.1mg/kg). The antimyotonic activity of drugs in vivo was linearly correlated with their potency in blocking hNav1.4 channels in vitro. Deviation was observed for propafenone and carbamazepine, likely due to pharmacokinetics and multiple targets. The comparison of the antimyotonic dose calculated in rats with the current clinical dose in humans strongly suggests that all the tested drugs may be used safely for the treatment of human myotonia. Considering the limits of mexiletine tolerability and the occurrence of non-responders, this study proposes an arsenal of alternative drugs, which may prove useful to increase the quality of life of individuals suffering from non-dystrophic myotonia. Further clinical trials are warranted to confirm these results. PMID:24613829

  13. Occurrence and removal of selected micropollutants in a water treatment plant.

    Science.gov (United States)

    Nam, Seung-Woo; Jo, Byung-Il; Yoon, Yeomin; Zoh, Kyung-Duk

    2014-01-01

    The levels of 14 micropollutants including nine pharmaceuticals, two pesticides, and three endocrine disruptors were measured in a water treatment plant (WTP) in Seoul, Korea. Among the measured micropollutants, 12 (excluding atrazine and triclocarban) were found in the influent and effluent from the WTP, at levels ranging from 2 to 482 ng L(-1). The removal efficiencies of the detected micropollutants in the WTP ranged from 6% to 100%. Among them diclofenac, acetaminophen, caffeine, carbamazepine, and 2,4-D were effectively removed (>80%). Metoprolol was unlikely to be removed (6%) in the WTP process. Concentrations of acetaminophen, metoprolol, ibuprofen, and naproxen were higher in winter, while levels of herbicides of 2,4-dichloro-phenoxyacetic acid (2,4-D) were higher in summer. Metoprolol was hardly removed in the water treatment process. Laboratory experiments showed that compounds with logKow>2.5 (especially bisphenol-A, 2,4-D, carbamazepine, triclocarban and 4-nonylphenol) were effectively removed by coagulation process, and adsorption effect increased in proportion with hydrophobicity of micropollutants and the turbidity of water. Sunlight photodegradation also effectively removed sulfamethoxazole, sulfamethazine, caffeine, diclofenac, ibuprofen, and acetaminophen, which are photosensitizes. Chlorination was relatively not effective for the removal of micropollutants due to the lower chlorine dosage (2 mg L(-1)), lower contact time (1h), and already lower levels of micropollutants at the chlorination stage at WTP. Our results imply that micropollutants during coagulation stage at WTP can be removed not only by coagulation itself, but also by adsorption to clay particle especially for high turbidity water, and by sunlight photodegradation in the areas open to the atmosphere. PMID:24074880

  14. An analysis of the dissipation of pharmaceuticals under thirteen different soil conditions.

    Science.gov (United States)

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

    2016-02-15

    The presence of human and veterinary pharmaceuticals in the environment is recognized as a potential threat. Pharmaceuticals have the potential to contaminate soils and consequently surface and groundwater. Knowledge of contaminant behavior (e.g., sorption onto soil particles and degradation) is essential when assessing contaminant migration in the soil and groundwater environment. We evaluated the dissipation half-lives of 7 pharmaceuticals in 13 soils. The data were evaluated relative to the soil properties and the Freundlich sorption coefficients reported in our previous study. Of the tested pharmaceuticals, carbamazepine had the greatest persistence (which was mostly stable), followed by clarithromycin, trimethoprim, metoprolol, clindamycin, sulfamethoxazole and atenolol. Pharmaceutical persistence in soils was mostly dependent on the soil-type conditions. In general, lower average dissipation half-lives and variability (i.e., trimethoprim, sulfamethoxazole, clindamycin, metoprolol and atenolol) were found in soils of better quality (well-developed structure, high nutrition content etc.), and thus, probably better microbial conditions (i.e., Chernozems), than in lower quality soil (Cambisols). The impact of the compound sorption affinity onto soil particles on their dissipation rate was mostly negligible. Although there was a positive correlation between compound dissipation half-life and Freundlich sorption coefficient for clindamycin (R=0.604, psoil-type conditions. Based on the calculated dissipation and sorption data, carbamazepine would be expected to have the greatest potential to migrate in the soil water environment, followed by sulfamethoxazole, trimethoprim and metoprolol. The transport of clindamycin, clarithromycin and atenolol through the vadose zone seems less probable.

  15. 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.

  16. Anticonvulsant medications attenuate amphetamine-induced deficits in behavioral inhibition but not decision making under risk on a rat gambling task.

    Science.gov (United States)

    Tremblay, Melanie; Winstanley, Catharine A

    2016-11-01

    Impulsivity is a major component of mania in bipolar disorder (BD), and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are observed in some patients with temporal lobe epilepsy (TLE), and incidence of problem gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of BD. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioral aspect targeted by these drugs. This project explored the effect of the three anticonvulsant drugs currently also used as mood stabilizers- carbamazepine, valproate and lamotrigine on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). In this task, rats choose between four distinct, probabilistic reinforcement schedules. Sugar pellet profits are maximized by adopting a conservative strategy, avoiding tempting high-risk, high-reward options. Effects of the anticonvulsant agents were assessed on baseline performance and also in conjunction with amphetamine administration, in order to approximate a "mania-like" state. Carbamazepine appeared to slow processing speed, decreasing premature responses and increasing choice latency, whereas valproate and lamotrigine had no effect. When administered prior to amphetamine, lamotrigine was the only drug that failed to attenuate the pro-impulsive effect of the psychostimulant. Further studies looking at chronic administration of anticonvulsants may help us understand the impact of this medication class on decision-making and impulsivity in healthy rats and disease models. PMID:27515288

  17. Surface characterisation and photocatalytic performance of N-doped TiO{sub 2} thin films deposited onto 200 nm pore size alumina membranes by sol–gel methods

    Energy Technology Data Exchange (ETDEWEB)

    Grilli, R., E-mail: r.grilli@surrey.ac.uk [The Surface Analysis Laboratory, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom); Di Camillo, D.; Lozzi, L. [Dipartimento di Scienze Fisiche e Chimiche, Università degli Studi dell' Aquila, Via Vetoio, 67010 Coppito, L' Aquila (Italy); Horovitz, I.; Mamane, H.; Avisar, D. [School of Mechanical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); Baker, M.A. [The Surface Analysis Laboratory, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom)

    2015-06-01

    Membrane filtration is employed for water treatment and wastewater reclamation purposes, but membranes alone are unable to remove pollutant molecules and certain pathogens. Photocatalytically active N-doped TiO{sub 2} coatings have been deposited by sol–gel onto 200 nm pore size alumina membranes for water treatment applications using two different methods, via pipette droplets or spiral bar applicator. The uncoated and coated membranes were characterised by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X-ray spectrometry (EDX). Both coatings showed the presence of N-doped anatase, with a surface coverage between 84 and 92%, and nitrogen concentration (predominantly interstitial) of 0.9 at.%. The spiral bar applicator deposited coatings exhibit a thicker mud-cracked surface layer with limited penetration of the porous membrane, whilst the pipette deposited coatings have mostly penetrated into the bulk of the membrane and a thinner layer is present at the surface. The photocatalytic activity (PCA), measured through the degradation of carbamazepine (CBZ), under irradiation of a solar simulator was 58.6% for the pipette coating and 63.3% for the spiral bar coating. These photocatalytically active N-doped sol–gel coated membranes offer strong potential in forming the fundamental basis of a sunlight based water treatment system. - Highlights: • Sol gel N-doped TiO{sub 2} thin films were deposited on 200 nm pore size Al{sub 2}O{sub 3} membranes. • Two sol–gel methods have been compared – pipette drop and spiral bar deposition. • The coatings showed a similar microstructure and composition but different morphology. • The PCA (degradation of carbamazepine) was ∼60% for both sol–gel coatings. • The coated membranes are promising for use in a membrane based water treatment system.

  18. Pharmacological evaluation of rat dorsal root ganglion neurons as an in vitro model for diabetic neuropathy

    Directory of Open Access Journals (Sweden)

    Eve Peeraer

    2011-02-01

    Full Text Available Eve Peeraer1,2, An Van Lutsenborg3, An Verheyen1,4, Raf De Jongh5, Rony Nuydens1, Theo F Meert1,21Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium; 2University Hasselt, Hasselt, Belgium; 3Free University Brussels, Brussels, Belgium; 4The Vesalius Research Center, University of Leuven, Leuven, Belgium; 5Intensive Care and Emergency Care, Ziekenhuis Oost-Limburg, Genk, BelgiumBackground: Diabetic neuropathy is a complication of diabetes mellitus that develops in about 50% of people with diabetes. Despite its widespread occurrence and devastating effects, this complication is still not fully understood, and there is no treatment available to prevent its development.Methods: In this study, immunocytochemistry for activating transcription factor 3, a marker for cell injury, was used to investigate the stress response in dorsal root ganglion neurons in both in vitro and ex vivo models of diabetic neuropathy.Results: Our findings showed increased activating transcription factor 3 expression in hyperglycemic culture conditions and in dorsal root ganglion neurons isolated from diabetic rats. Glial cell line-derived neurotrophic factor, a substance with known neuroprotective properties, was able to reduce diabetes mellitus-induced neuronal stress in vitro, while gabapentin and carbamazepine, currently used to treat neuropathic pain, showed only limited effects.Conclusion: Growth factors may have a therapeutic benefit as neurotrophic agents in the treatment of diabetic peripheral neuropathy, but gabapentin and carbamazepine have no direct protective effect on sensory neurons. This research also indicates that immunocytochemistry for activating transcription factor 3 is a valuable tool for evaluation of pharmacological substances in dorsal root ganglion cultures.Keywords: diabetic peripheral neuropathy, dorsal root ganglion, activating transcription factor 3, glial cell line-derived neurotrophic factor, anticonvulsants

  19. Determination of micro-organic contaminants in groundwater (Maribor, Slovenia).

    Science.gov (United States)

    Koroša, A; Auersperger, P; Mali, N

    2016-11-15

    Micro-organic (MO) contaminants in groundwater can have adverse effects on both the environment and on human health. They enter the natural environment as a result of various processes, their presence in groundwater is the result of current anthropogenic activity and pollution loads from the past. A study on the occurrence and concentrations levels of selected contaminants in water was performed in the city of Maribor, Slovenia. A total of 56 groundwater and 4 surface water samples were collected in together four rounds in different hydrogeological periods (dry and wet seasons), and a total of 13 selected contaminants were analysed in this study. Carbamazepine, propyphenazone, caffeine, 2-methyl-2H-benzotriazole (2-MBT) and 2.4-dimethyl-2H-benzotriazole (2.4-DMBT) were determined as indicators of urban pollution, while pesticides and their metabolites (atrazine, desethylatrazine, deisopropylatrazine, terbuthylazine, desethylterbuthylazine, metolachlor, simazine, propazine) were mainly defined as indicators of crop production. All of the selected MO contaminants were detected both in the aquifer and Drava River. The most frequently detected MO compounds in groundwater were desethylatrazine (frequency of detection 98.2%; max. concentration 103.0ngL(-1)), atrazine (94.6%; 229ngL(-1)), 2.4-DMBT (92.9%; 273ngL(-1)), carbamazepine (80.4%; 88.00ngL(-1)), desethylterbuthylazine (76.8%; 7.0ngL(-1)) and simazine (76.8%; 29.6ngL(-1)), whereas propyphenazone (14.3%; 10.7ngL(-1)) was the least frequently detected. Detected MO concentrations in the study were compared with results published elsewhere around the world. Concentrations in groundwater indicate specific land use in their recharge areas. On the basis of correlations and the spatial distribution of selected MOs, groundwater origin for every sampling point was determined. Sampling sites were divided into three different groups for which indicative groundwater quality properties were defined. PMID:27395079

  20. Determining the isotopic abundance of a labeled compound by mass spectrometry and how correcting for natural abundance distribution using analogous data from the unlabeled compound leads to a systematic error.

    Science.gov (United States)

    Schenk, David J; Lockley, William J S; Elmore, Charles S; Hesk, Dave; Roberts, Drew

    2016-04-01

    When the isotopic abundance or specific activity of a labeled compound is determined by mass spectrometry (MS), it is necessary to correct the raw MS data to eliminate ion intensity contributions, which arise from the presence of heavy isotopes at natural abundance (e.g., a typical carbon compound contains ~1.1% (13) C per carbon atom). The most common approach is to employ a correction in which the mass-to-charge distribution of the corresponding unlabeled compound is used to subtract the natural abundance contributions from the raw mass-to-charge distribution pattern of the labeled compound. Following this correction, the residual intensities should be due to the presence of the newly introduced labeled atoms only. However, this will only be the case when the natural abundance mass isotopomer distribution of the unlabeled compound is the same as that of the labeled species. Although this may be a good approximation, it cannot be accurate in all cases. The implications of this approximation for the determination of isotopic abundance and specific activity have been examined in practice. Isotopically mixed stable-atom labeled valine batches were produced, and both these and [(14) C6 ]carbamazepine were analyzed by MS to determine the extent of the error introduced by the approach. Our studies revealed that significant errors are possible for small highly-labeled compounds, such as valine, under some circumstances. In the case with [(14) C6 ]carbamazepine, the errors introduced were minor but could be significant for (14) C-labeled compounds with particular isotopic distributions. This source of systematic error can be minimized, although not eliminated, by the selection of an appropriate isotopic correction pattern or by the use of a program that varies the natural abundance distribution throughout the correction. PMID:26916110