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Sample records for theophylline

  1. Extracorporeal treatment for theophylline poisoning

    DEFF Research Database (Denmark)

    Ghannoum, Marc; Wiegand, Timothy J; Liu, Kathleen D

    2015-01-01

    pharmacokinetic studies, yielding a low-to-very-low quality of evidence for all recommendations. Data on 143 patients were reviewed, including 10 deaths. The workgroup concluded that theophylline is dialyzable (level of evidence = A) and made the following recommendations: ECTR is recommended in severe...... theophylline poisoning (1C). Specific recommendations for ECTR include a theophylline concentration [theophylline] > 100 mg/L (555 μmol/L) in acute exposure (1C), the presence of seizures (1D), life-threatening dysrhythmias (1D) or shock (1D), a rising [theophylline] despite optimal therapy (1D), and clinical...

  2. Acute Theophylline Intoxication: Case Report

    Directory of Open Access Journals (Sweden)

    Zehra Baykal Tutal

    2016-01-01

    Full Text Available Theophylline is an efficient bronchodilatator, which is used in the treatment of the disease such like Chronic Obstructive Pulmoner Disease (COPD neonatal apnea, bradycardial syndrome. Blood levels of theophylline above 15 ug/ml have risk of intoxication. Acute and chronic intoxication can be seen. Nausea, vomitin, agitation, palpitation and metabolic abnormalities such as, hyperglisemia, hypokalemia, impairment in acid base equilibrium and leukocytosis can be seen in acute theophylline intoxication. Acute theophylline intoxications can result life threatening situations such as convulsions, ventricular arrhythmias and death. Theophylline intoxications are often iatrogenic. In this case, the clinical course of a patient with COPD who took theophylline with the intention of suicide attempt is to mentioned and discussion of diagnosis, treatment and clinical course of acute theophylline intoxication was to aimed.

  3. Evaluation of Controlled Release Theophylline Microspheres ...

    African Journals Online (AJOL)

    Erah

    Purpose: To formulate theophylline microspheres with cellulose acetate using solvent evaporation method and evaluate the effect of various processing factors on their characteristics. Methods: Microspheres containing theophylline were prepared with a hydrophilic, biocompatible polymer - cellulose acetate - by an ...

  4. Compound list: theophylline [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available theophylline TEO 00096 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/theophylline....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/theophylline....jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/theophylline.Rat.in_vivo.Liver.Repeat.zip ... ...vo/Liver/Single/theophylline.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi

  5. Doxofylline is not just another theophylline!

    Science.gov (United States)

    Matera, Maria Gabriella; Page, Clive; Cazzola, Mario

    2017-01-01

    Doxofylline, which differs from theophylline in containing the dioxalane group at position 7, has comparable efficacy to theophylline in the treatment of respiratory diseases, but with an improved tolerability profile and a favorable risk-to-benefit ratio. Furthermore, it does not have significant drug-drug interactions as exhibited with theophylline, which make using theophylline more challenging, especially in elderly patients with co-morbidities receiving multiple classes of drug. It is now clear that doxofylline also possesses a distinct pharmacological profile from theophylline (no significant effect on any of the known phosphodiesterase isoforms, no significant adenosine receptor antagonism, no direct effect on histone deacetylases, interaction with β2-adrenoceptors) and therefore, should not be considered as just a modified theophylline. Randomized clinical trials of doxofylline to investigate the use of this drug to reduce exacerbations and hospitalizations due to asthma or COPD as an alternative to expensive biologics, and certainly as an alternative to theophylline are to be encouraged.

  6. Evaluation of theophylline therapeutic drug monitoring service

    Directory of Open Access Journals (Sweden)

    Neža Rugelj

    2015-05-01

    Full Text Available BackgroundTherapeutic monitoring of theophylline serum levels is required due to its narrow therapeutic range and marked interindividual pharmacokinetic variability. We evaluated therapeutic drug monitoring service for theophylline in Slovenian clinical setting, which currently includes no pharmacokinetic evaluation of measured theophylline serum concentrations. MethodsWe  retrospectively evaluated 127 randomly selected theophylline serum level determinations performed in 2010 in a tertiary clinical setting in Slovenia. Demographic data, information on theophylline dosing and blood sampling was collected from patients’ data files. Authors evaluated the appropriateness of the following procedures: indications for theophylline serum concentration measurement, timing of blood sampling and dosage adjustments made after theophylline levels had been reported. On the basis of collected data, population pharmacokinetic model for theophylline was built and further used for the evaluation of dosage adjustments. ResultsOut of 127 cases, 107 (84.3% had clinically justified indication for theophylline serum level measurement. Near half of measurements (44.9% were performed before the steady state of theophylline concentrations was established. 65% of measured concentrations were subtherapeutic and the average measured concentration was below therapeutic range (53.1 μmol/L. Despite subtherapeutic concentrations the dose of theophylline was mainly not increased. Pharmacokinetic model enabled the calculation of average optimal daily dose which was significantly higher than the average actual daily dose used (876 mg vs. 572 mg, p < 0.001. ConclusionsTheophylline TDM service should be optimized and pharmacokinetic interpretation of theophylline serum levels should be integrated into clinical practice.

  7. Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects.

    Science.gov (United States)

    Gregoire, S L; Grasela, T H; Freer, J P; Tack, K J; Schentag, J J

    1987-01-01

    The influence of multiple doses of ofloxacin (ORF 18489) on the disposition of theophylline was studied in 15 male volunteers. Subjects were confined in the Clinical Research Unit for 13 days and given a xanthine-free diet. A single dose (3 mg/kg) of theophylline was given orally, and blood samples were collected at fixed time intervals for 36 h. The concentrations of theophylline were measured with TDX (Abbott Diagnostics, Irving, Tex.), and clearance was calculated. Theophylline clearance was used to individualize subsequent doses to achieve average steady-state theophylline concentrations in plasma of 10 mg/liter. Individualized theophylline doses were administered every 8 h until steady-state conditions were reached. Theophylline clearance was determined again at steady state and on days 7 and 8. On day 8, ofloxacin (400 mg every 12 h) was given concomitantly with theophylline. Theophylline clearance was measured again on day 12, after the last theophylline dose. Administration of ofloxacin for 1 day did not change theophylline clearance, but coadministration for 4 days significantly decreased theophylline clearance by 12.1% (P less than 0.05). The area under the concentration-time curve for theophylline increased 9.9% (P less than 0.05), and average steady-state concentrations in plasma increased 10.3% (P less than 0.05). Despite changes in clearance, adverse effects of theophylline did not increase during coadministration of ofloxacin. Although statistically significant, the interaction between ofloxacin and theophylline is unlikely to be of major clinical importance. PMID:3472488

  8. Doxofylline is not just another theophylline!

    Directory of Open Access Journals (Sweden)

    Matera MG

    2017-12-01

    Full Text Available Maria Gabriella Matera,1 Clive Page,2 Mario Cazzola3 1Department of Experimental Medicine, Unit of Pharmacology, University of Campania ‘Luigi Vanvitelli’, Naples, Italy; 2Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, King’s College London, London, UK; 3Department of Experimental Medicine and Surgery, Chair of Respiratory Medicine, University of Rome ‘Tor Vergata’, Rome, Italy Abstract: Doxofylline, which differs from theophylline in containing the dioxalane group at position 7, has comparable efficacy to theophylline in the treatment of respiratory diseases, but with an improved tolerability profile and a favorable risk-to-benefit ratio. Furthermore, it does not have significant drug–drug interactions as exhibited with theophylline, which make using theophylline more challenging, especially in elderly patients with co-morbidities receiving multiple classes of drug. It is now clear that doxofylline also possesses a distinct pharmacological profile from theophylline (no significant effect on any of the known phosphodiesterase isoforms, no significant adenosine receptor antagonism, no direct effect on histone deacetylases, interaction with β2-adrenoceptors and therefore, should not be considered as just a modified theophylline. Randomized clinical trials of doxofylline to investigate the use of this drug to reduce exacerbations and hospitalizations due to asthma or COPD as an alternative to expensive biologics, and certainly as an alternative to theophylline are to be encouraged. Keywords: doxofylline, theophylline, mechanisms of action, therapeutic effects, adverse effects

  9. Cyclosporine enhances theophylline neurotoxicity in rats.

    Science.gov (United States)

    Hoffman, A; Pinto, E; Afargan, M; Schattner, A

    1994-04-01

    Treatment with cyclosporine may be associated with adverse central nervous system (CNS) effects as well as with the potentiation of effects of certain other drugs. In particular, theophylline-induced seizures, which are often fatal and occur unpredictably over a wide range of serum theophylline concentrations, may be precipitated. To study this interaction, adult rats that were injected with cyclosporine or placebo (50 mg/kg in a single dose or on each of four consecutive days) received a constant infusion of theophylline (2 mg/min iv) until the onset of maximal seizures. At that time, blood, cerebrospinal fluid (CSF), and brain tissue samples were obtained for theophylline concentration determinations by HPLC, as well as for measurement of several biochemical parameters in the serum. Consecutive cyclosporine administration (but not a single dose) reduced serum protein levels. There was a small increase in theophylline sensitivity after a single dose of cyclosporine. The CSF theophylline concentrations at the onset of seizures were 215 +/- 10 vs 202 +/- 5 mg/L (P theophylline concentrations required to produce convulsions (231 +/- 8 vs 191 +/- 10, P theophylline toxicity and increase the risk for generalized seizures.

  10. Theophylline: Adverse Effects, Poisoning and Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Muhammed Charehsaz

    2011-09-01

    Full Text Available Abstract: Theophylline, which is a methylxanthine derivative, has been commonly used in all over the world for many years due to its cheapness and effectiveness in treatment of asthma and chronic obstructive pulmonary disease (COPD. There is a close relationship between its bronchodilator effect and blood levels of theophylline. Maintenance of its blood level between 10-20 μg/ml is important to obtain a maximum bronchodilator effect. Besides having a narrow therapeutic range, its alteration of pharmacokinetic characteristics due to individually factors, drugs, diet, and habits such as smoking and alcohol has led to requirement of more carefully use of theophylline for patients at every age. In the present review article, in addition to pharmacokinetic/ dynamic properties of theophylline, its adverse effects, poisoning with over dose of theophylline and approaches of its treatment have been given.

  11. Study of theophylline stability on polymer matrix

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Kiriaki M.S.; Parra, Duclerc F.; Oliveira, Maria Jose A.; Bustillos, Oscar V.; Lugao, Ademar B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], E-mail: strassacapa@uol.com.br

    2007-07-01

    Theophylline is a bronchodilator, commonly known and used as a drug model in the development of pharmaceutical formulations. The stability of the drug and the matrix, scope of this study, was evaluated in the solid formulation. Polymeric matrix based on PHB containing the drug (theophylline) was prepared and submitted to radiation sterilization at different doses of: 5, 10, 20 and 25 kGy using a Cobalt- 60 source. The modified drug release of theophylline sterilized tablets has been studied. Modern techniques of HPLC (High Pressure Liquid Chromatography), DSC (Differential scanning calorimetry) and TGA (Thermogravimetry analysis) were employed. The results have shown the influence of sterilization by radiation process in both the theophylline and the polymeric drug delivery matrix samples. The increasing of polymeric matrix crosslinking under radiation conditions retards the drug release while the theophylline structure is stable under the radiation (author)

  12. Are phosphodiesterase 4 inhibitors just more theophylline?

    Science.gov (United States)

    Boswell-Smith, Victoria; Cazzola, Mario; Page, Clive P

    2006-06-01

    Theophylline has been relegated to a second- or even third-line therapy in the treatment of asthma and chronic obstructive pulmonary disease (COPD), behind glucocorticosteroids and beta2-agonists, although recent findings have suggested that theophylline possesses anti-inflammatory and immunomodulatory effects in addition to its well-recognized effects as a bronchodilator. In part, theophylline has fallen out of favor because of its adverse side-effect profile, and this has led to the search for more effective and safer drugs based on the knowledge that theophylline is orally active and that it is a nonselective phosphodiesterase (PDE) inhibitor. This has led to the development of selective PDE4 inhibitors, originally designed for depression, for the treatment of both COPD and asthma. Such drugs have shown clinical efficacy in the treatment of respiratory disease while having a considerably safer side-effect profile in comparison with theophylline, particularly because there are no reported drug interactions with PDE4 inhibitors, a feature that complicates the use of theophylline. In addition, it is also becoming increasingly apparent that theophylline is not working solely through PDE inhibition, as formerly assumed, and that this drug has other relevant pharmacologic activities that are likely to contribute to its efficacy, such as adenosine receptor antagonism and induction of histone deacetylase. Thus, the introduction of PDE4 inhibitors represents an entirely new class of drugs for the treatment of respiratory disease.

  13. Theophylline in the Treatment of Cancer

    Directory of Open Access Journals (Sweden)

    Tanseli Efeoğlu Gönlügür

    2007-01-01

    Full Text Available Theophylline is a drug used for the treatment of obstructive airway diseases. It inhibits the enzyme phosphodiesterase, thereby preventing the intracellular break-down of cyclic AMP. Potentially beneficial therapeutic effects of theophylline include bronchial smooth-muscle relaxation, enhanced mucociliary transport, decrease in pulmonary hypertension, improved diaphragmatic contractility, and central stimulation of ventilation. On the other hand, theophylline evokes a concentration- and time-dependent decrease in DNA synthesis in human breast cancer cells. Theophylline-treated melanoma cells exhibit low adhesion to laminin/collagen type IV. Consequently, theophylline possesses the capacity to inhibit not only cell proliferation, but also the metastatic behaviour of melanoma cells. This drug prevents neovascularization of the tumor by blocking endothelial cell proliferation. The combination of theophylline with cytotoxic drugs may permit a reduction in the effective dose needed in chemotherapy treatment of lung cancer patients. It has also a prophylactic effect on the nephrotoxicity due to cisplatin. However, this drug may inhibit small cell lung cancer cells but stimulate pulmonary adenocarcinoma cells. It is necessary to perform large, prospective studies for the exact role of theophylline on each type of lung cancer.

  14. Theophylline

    Science.gov (United States)

    ... and other lung diseases. It relaxes and opens air passages in the lungs, making it easier to ... cimetidine (Tagamet), ciprofloxacin (Cipro), clarithromycin (Biaxin), diuretics ('water pills'), erythromycin, lithium (Eskalith, Lithobid), oral contraceptives, phenytoin (Dilantin), ...

  15. Theophylline: a review of population pharmacokinetic analyses.

    Science.gov (United States)

    Ma, Y J; Jiang, D Q; Meng, J X; Li, M X; Zhao, H H; Wang, Y; Wang, L Q

    2016-12-01

    Numerous population pharmacokinetic studies of theophylline have been conducted in paediatric and adult patients. The purpose of this review was to summarize the published studies concerning population pharmacokinetics of theophylline in patients of different ages and discuss factors that might cause the large variability in the pharmacokinetics of theophylline. A literature search was conducted in PubMed using the following keywords: 'theophylline', 'population pharmacokinetic(s)' and 'nonlinear mixed effect model'. Additionally, the relevant references listed in the retrieved articles were manually reviewed. All of the studies that reported the population pharmacokinetics of theophylline in humans were included in this review. However, articles were excluded if they were not written in English. Sixteen articles were included in this review. Among them, 11 were conducted on paediatric patients, and five were conducted on adults. A one-compartment model with first-order elimination was employed in most of the included articles. A nonlinear mixed effect modelling approach (NONMEM) was the most commonly used software to develop a population pharmacokinetic model. Body weight and age (post-conceptional age and post-natal age) were the most important factors associated with the clearance (CL) of theophylline in paediatric patients. Body weight (ideal body weight and lean body mass), age and smoking status were most frequently used to estimate the CL of theophylline in adults. The median (range) estimate values of CL for paediatric and adult patients were 0·062 (0·0056-0·0949) L/h/kg and 0·053 (0·0493-0·0517) L/h/kg, respectively. The median values of the interindividual variability of CL were 33·5% in adults and 25·8% in paediatric patients. The mean values of the residual variability were 21% in paediatric patients and 14·3% in adults. This review concludes that body weight and age were the most important factors associated with the clearance of theophylline

  16. Treatment of theophylline intoxication using continuous venovenous haemofiltration

    NARCIS (Netherlands)

    Koeijers, J.J.; Verhoeven, C.L.; Boersma, H.H.; van Mook, W.N.K.A

    2008-01-01

    Theophylline intoxication can cause serious complications such as seizures, cardiac arrhythmias and eventually cardiac arrest. Because of these potentially life-threatening clinical manifestations of theophylline intoxication, treatment methods that rapidly eliminate the drug are essential. These

  17. differential pulse voltammetric determination of theophylline at poly ...

    African Journals Online (AJOL)

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    DIFFERENTIAL PULSE VOLTAMMETRIC DETERMINATION OF. THEOPHYLLINE AT ... KEY WORDS: Cyclic voltammetry, Differential pulse voltammetry, Theophylline, 4-Amino-3- hydroxynaphthalene sulfonic acid ... serious toxicity, including vomiting, tachycardia, seizures and central nervous system excitation [1, 4, 5].

  18. Luminescence characteristics of caffeine and theophylline1

    Science.gov (United States)

    Andino, M. M.; De Lima, C. G.; Winefordner, J. D.

    The luminescence properties of solutions of caffeine and theophylline in methanol are observed. The effects of the solvent pH, the presence of a heavy atom and the matrix or substrate on the fluorescence and phosphorescence properties of the compounds are evaluated. Caffeine and theophylline fluorescence can be observed at room temperature from dilute methanolic solutions and strong phosphorescence is observed at low temperature when the matrix is in a polycrystalline state. Acidic and basic media cause spectral changes and reduce the intensity of the low temperature phosphorescence. Iodide is a good heavy-atom enhancer of both the low temperature and room temperature phosphorescence of caffeine and theophylline. The intensity of the phosphorescence at room temperature and when spotted on filter paper depends on the type of filter paper and the pH of the spotting solution and/or the pH of the wet surface at the moment of spotting. Theophylline is more sensitive than caffeine to the microenvironment. Under the appropriate experimental conditions, both low temperature and room temperature phosphorescence could be used as analytical tools for the determination of caffeine and theophylline.

  19. Evaluation of Controlled Release Theophylline Microspheres ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research ... Methods: Microspheres containing theophylline were prepared with a hydrophilic, biocompatible polymer - cellulose acetate - by an emulsion solvent evaporation technique using an acetone/liquid paraffin system containing Span 80 as a surfactant. The effect of processing ...

  20. Effects of theophylline administration and intracranial abnormalities ...

    African Journals Online (AJOL)

    Objective: To determine effects of theophylline therapy for recurrent apnoea of prematurity and abnormal early (within the first 24 hours) cranial ultrasound abnormalities on protective neck turning response in preterm infants. Design: A cross sectional descriptive study. Setting: The Neonatal Unit of Hammersmith Hospital, ...

  1. Theophylline effects in patients with syndrome X

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    Sadeghian H

    2000-08-01

    Full Text Available A role of adenosine in pathogenesis of syndrome X has recently been postulated. Previous studies suggest that aminophylline (An adenosine receptor blocker improves exercise tolerance in this disorder. Present study was performed to examine the efficacy of Theophylline in syndrome X and to determine the incidence of cardiovascular risk factors and clinical, ECG and angiographic findings in these patients. 31 patients were studied. The first 16 patients received Theophylline. Other 15 cases received placebo. Exercise tolerance test was repeated after 1-2 weeks. Patients who received Theophylline had increase in rate-pressure product at peak exercise and decrease in symptoms during exercise, but stage of st depression, global and peak st depression, exercise tolerance and persistence of st depression more than 3 minutes in recovery and symptoms of patients in general were not significant different. Theophylline has a favorable effect on exercise, reduces chest pain and rate-pressure product at peak exercise in patients with syndrome X, but not on other variables of exercise test.

  2. Theophylline and dyphylline pharmacokinetics in the horse.

    Science.gov (United States)

    Ayres, J W; Pearson, E G; Riebold, T W; Chang, S F

    1985-12-01

    The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 hours. Clearance was 42.3 to 69.2 ml/hr/kg. The initial distribution phase was rapid (t1/2 approx 3.5 to 4 minutes); a 2nd distribution phase was slower (t1/2 approx 1.5 to 2 hours). Plasma concentrations of theophylline were in the assumed effective range (10 to 20 micrograms/ml) from 15 minutes until 40 minutes after time zero. The mean apparent volume of distribution was 1.02 L/kg. After bolus IV injection of dyphylline (20 mg/kg), pharmacokinetics were best described by a 2-compartment open model in 2 horses and by a 3-compartment open model in 4 horses. In the 6 horses, elimination half-life of dyphylline was 1.9 to 2.9 hours, and clearance was 200 to 320 ml/hr/kg. Plasma concentrations (approx 50 micrograms/ml) were observed at 10 minutes after injection without adverse effects. Concentrations greater than 10 micrograms/ml were observed from time zero to about 1.5 hours after injection. Theophylline induced significant increases in heart rate, but dyphylline did not affect heart rate significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Molecularly Imprinted Polymer Based Sensor for the Detection of Theophylline

    Science.gov (United States)

    Braga, Guilherme S.; Paterno, Leonardo G.; Fonseca, Fernando J.; del Valle, Manel

    2011-11-01

    A molecularly imprinted polymer (MIP) impedance-based sensor was employed to detect theophylline in distilled water. To evaluate its sensibility, impedance measurements were carried out in a diluted solution of theophylline (1 mM) and distilled water using MIP and NIP (reference non-imprinted polymer) sensors. MIP showed higher sensitivity to theophylline than the NIP. This feature shows their suitability for developing an electronic tongue system for determination of methylxanthines.

  4. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study.

    Science.gov (United States)

    Henkin, Robert I; Schultz, Michael; Minnick-Poppe, Laura

    2012-11-01

    To determine whether intranasal theophylline methylpropyl paraben can correct hyposmia and hypogeusia. We performed an open-label pilot study in patients with hyposmia and hypogeusia under the following 3 conditions: (1) before treatment, (2) after oral theophylline anhydrous treatment, and (3) after intranasal theophylline treatment. Under each condition, we performed subjective evaluations of taste and smell functions, quantitative measurements of taste (gustometry) and smell (olfactometry), and measurements of serum theophylline level and body weight. The Taste and Smell Clinic in Washington, DC. Ten patients with hyposmia and hypogeusia clinically related to the effects of viral illness, allergic rhinitis, traumatic brain injury, congenital hyposmia, and other chronic disease processes were selected. Oral theophylline anhydrous, 200 to 800 mg/d for 2 to 12 months, was administered to each patient. This treatment was discontinued for 3 weeks to 4 months when intranasal theophylline methylpropyl paraben, 20 μg/d in each naris, was administered for 4 weeks. At termination of each condition, taste and smell function was determined subjectively, by means of gustometry and olfactometry, with measurement of serum theophylline levels and body weight. Oral theophylline treatment improved taste and smell acuity in 6 patients after 2 to 12 months of treatment. Intranasal theophylline treatment improved taste and smell acuity in 8 patients after 4 weeks, with improvement greater than after oral administration. No adverse effects accompanied intranasal drug use. Body weight increased with each treatment but was greater after intranasal than after oral administration. Intranasal theophylline treatment is safer and more effective in improving hyposmia and hypogeusia than oral theophylline anhydrous treatment.

  5. Theophylline-nicotinamide cocrystal formation in physical mixture during storage.

    Science.gov (United States)

    Ervasti, Tuomas; Aaltonen, Jaakko; Ketolainen, Jarkko

    2015-01-01

    Pharmaceutically relevant properties, such as solubility and dissolution rate, of active pharmaceutical ingredients can be enhanced by cocrystal formation. Theophylline and nicotinamide are known to form cocrystals, for example if subjected to solid-state grinding. However, under appropriate conditions, cocrystals can also form in physical mixtures without any mechanical activation. The purpose of this work was to study whether theophylline and nicotinamide could form cocrystals spontaneously, without mechanical activation. Crystalline theophylline and nicotinamide powders were gently mixed manually in a 1:1 molar ratio and stored at different relative humidity and temperature conditions. The solid state of the samples was analyzed by differential scanning calorimetry, Raman spectroscopy and X-ray powder diffractometry. Three different variations of theophylline were used as starting materials, e.g., two size fractions of theophylline anhydrate (large 710 μm-1 mm and small 180-355 μm), and monohydrate (recrystallized from water). As a reference, anhydrous theophylline-nicotinamide cocrystals were prepared by solid-state grinding. The results of this study indicate that theophylline-nicotinamide cocrystals can form without any mechanical activation from physical mixtures of theophylline and nicotinamide during storage. For anhydrous samples, storage humidity was found to be a critical parameter for cocrystal formation. Increasing temperature was also found to have an accelerating effect on the transformation. The effect of particle size of anhydrous theophylline on the transformation rate could not be completely resolved; DSC and Raman indicated slightly faster transformation with a physical mixture prepared from large size fraction of anhydrous theophylline, but the differences were only minor. Cocrystal formation was also observed in the physical mixture prepared from theophylline monohydrate, but the rate was not as high as with samples prepared from anhydrous

  6. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    during the early hours of the morning and nocturnal asthma attacks are therefore not always prevented.2 However, improved control of nocturnal asthma has been reported with the use of once-daily, sustained-release, evening- administered theophylline.1. The influence of theophylline on sleep is not clear and.

  7. Structural features of DNA interaction with caffeine and theophylline

    Science.gov (United States)

    Nafisi, Shohreh; Manouchehri, Firouzeh; Tajmir-Riahi, Heidar-Ali; Varavipour, Maryam

    2008-03-01

    Caffeine and theophylline are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. However, there has been no information on the interactions of these xanthine derivatives with individual DNA at molecular level. The aim of this study was to examine the stability and structural features of calf-thymus DNA complexes with caffeine and theophylline in aqueous solution, using constant DNA concentration (6.25 mM) and various caffeine or theophylline/DNA(P) ratios of 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. FTIR, UV-visible spectroscopic methods were used to determine the ligand external binding modes, the binding constant and the stability of caffeine, theophylline-DNA complexes in aqueous solution. Spectroscopic evidence showed that the complexation of caffeine and theophylline with DNA occurred via G-C and A-T and PO 2 group with overall binding constants of K(caffeine-DNA) = 9.7 × 10 3 M -1 and K(theophylline-DNA) = 1.7 × 10 4 M -1. The affinity of ligand-DNA binding is in the order of theophylline > caffeine. A partial B to A-DNA transition occurs upon caffeine and theophylline complexation.

  8. Interaction of Ketotifen Fumarate with Anhydrous Theophylline in ...

    African Journals Online (AJOL)

    Purpose: The purpose of the present study was to investigate interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH. Methods: By using Job's continuous-variation analysis and Ardon's spectrophotomeric methods, the values of stability constants of theophylline with ketotifen ...

  9. Theophylline Increases the Uptake of Radioiodine by Mouse Thyroid

    Science.gov (United States)

    Caturegli, Patrizio; Ladenson, Paul W.

    2004-01-01

    Diagnostic and therapeutic use of radioiodine in the management of thyroid disorders depends on the ability of thyroid cells to concentrate radioiodine, a process that is regulated by the intracellular increase in cAMP. We hypothesized that theophylline, a drug known to increase intracellular cAMP via inhibition of phosphodiesterase, could increase thyroidal radioiodine uptake. We tested this effect in vivo, using C57BL/6j mice, and in vitro, using Fisher rat thyroid (FRTL-5) cells. One mouse received 2.5mg theophylline i.p., whereas a control mouse received only saline. Twenty-hours after theophylline, mice were injected with 10 µCi Na125I in 0.1 mL saline through the tail vein. Mean thyroidal 125I activity was 3.3-fold higher in theophylline-treated mice than in their respective controls. Radioiodine uptake and intracellular cAMP production of FRTL-5 cells were increased by a relatively low concentration of theophylline (1 µM). Intracellular cAMP increased up to 30 min and then declined in response to 1 µM theophylline. Sera from theophylline-treated mice stimulated 125I uptake and intracellular cAMP production by FRTL-5 cells. These findings show that theophylline can enhance radioiodine uptake by thyrocytes in vivo and in vitro. The in vitro effects of theophylline on both radioiodine uptake and cAMP production in a dose-dependent manner are consistent with an action mediated by phosphodiesterase inhibition. PMID:15483348

  10. Theophylline potentiates lipopolysaccharide-induced NO production in cultured astrocytes.

    Science.gov (United States)

    Ogawa, Mizue; Takano, Katsura; Kawabe, Kenji; Moriyama, Mitsuaki; Ihara, Hideshi; Nakamura, Yoichi

    2014-01-01

    Elucidation of the functions of astrocytes is important for understanding of the pathogenic mechanism of various neurodegenerative diseases. Theophylline is a common drug for bronchial asthma and occasionally develops side-effects, such as acute encephalopathy; although the pathogenic mechanism of the side-effects is unknown. The lipopolysaccharide (LPS)-induced nitricoxide (NO) production is generally used for an index of the activation of astrocyte in vitro. In this study, in order to elucidate the effect of theophylline on the astrocytic functions, we examined the LPS-induced NO production and the expression of iNOS in cultured rat cortex astrocytes.Theophylline alone could not induce the NO production; however, NO production induced by LPS was enhanced by theophylline in a dose-dependent manner; and by isobutylmethylxanthine, a phosphodiesterase inhibitor. The theophylline enhancement of LPS-induced NO production was further increased by dibutyryl cyclic AMP, a membrane-permeable cAMP analog; and by forskolin, an adenylate cyclase activator. When the cells were preincubated with Rp-8-Br-cAMP, an inhibitor of protein kinase A, the theophylline enhancement of LPS-induced NO production was decreased. The extent of iNOS protein expression induced by LPS was also enhanced by theophylline.It is likely that phosphodiesterase inhibition is a major action mechanism for the theophylline enhancement of LPS-induced NO production in astrocytes. Theophylline-induced acute encephalopathy might be due to the hyper-activation of astrocytes via cAMP signaling to produce excess amount of NO.

  11. The interaction of the theophylline metastable phase with water vapor

    Science.gov (United States)

    Matvienko, A. A.; Boldyrev, V. V.; Sidel'Nikov, A. A.; Chizhik, S. A.

    2008-07-01

    The conditions of hydration of the stable and metastable theophylline phases were determined. Two-phase metastable phase/monohydrate and stable phase/monohydrate equilibrium pressures were measured at 25, 30, and 35°C. The metastable phase began to react with water vapor at lower relative humidities than the stable phase. Processes that occurred with the metastable and stable theophylline phases over various water pressure ranges were considered. The metastable phase exhibited an unusual behavior at 25°C and relative humidity 47%. At constant water vapor pressure and temperature, theophylline was initially hydrated and then lost water and again became anhydrous. Two consecutive processes occurred in the system, the formation of theophylline monohydrate from the metastable phase and its decomposition to the stable phase. The ratio between the rates of these processes determined the content of the monohydrate at the given time moment.

  12. Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

    Science.gov (United States)

    Trépanier, Eric F.; Nafziger, Anne N.; Amsden, Guy W.

    1998-01-01

    Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident. PMID:9517954

  13. Re-evaluation of saliva for monitoring theophylline concentrations.

    OpenAIRE

    Rylance, G W; Beswick, D T; Cullen, R. E.; Roberts, D G

    1985-01-01

    Variability of the mixed saliva/plasma theophylline relation was examined in seven children aged 2 to 13 years. Good correlation between plasma and saliva concentrations was found, but on the three occasions there was considerable inter- and intrapatient variability. There was no significant or consistent relation between unstimulated and stimulated saliva concentrations or between saliva concentrations and sample volumes. Plasma theophylline concentrations cannot be predicted accurately from...

  14. Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline

    Science.gov (United States)

    Dilger, Karin; Zheng, Zhichang; Klotz, Ulrich

    1999-01-01

    Aims Theophylline is a model substrate of cytochrome P4501A2. The ability of the proton pump inhibitors (PPI) omeprazole, lansoprazole and pantoprazole to induce cytochrome P4501A2 has not yet been unequivocally resolved. The aim of this comprehensive study was to compare directly the effect of the three PPI on the absorption and disposition of theophylline. Methods Twenty healthy, nonsmoking, male and female volunteers (extensive metabolisers of cytochrome P4502C19 and Helicobacter pylori negative) participated in a randomized, double-blind, four-period, placebo-controlled crossover study. In each of the four periods they received either omeprazole (40 mg), lansoprazole (60 mg), pantoprazole (80 mg) or placebo once daily for 10 days. Sustained release theophylline (350 mg twice daily) was coadministered from day 8–10. Pharmacokinetics of theophylline as well as of all three PPI were determined at steady-state (day 10). Results In all periods, point estimates and 90% confidence intervals of the area under the concentration-time curves (AUC), maximum steady-state concentrations and peak-trough fluctuations of theophylline were not altered by PPI pretreatment and met the required limits for bioequivalence. Point estimates (90% confidence intervals) of the AUC ratios of theophylline plus PPI to theophylline alone were 0.92 (0.87–0.97), 0.90 (0.85–0.95) and 1.00 (0.95–1.06) for omeprazole, lansoprazole and pantoprazole, respectively. Conclusions Concomitant intake of omeprazole, lansoprazole or pantoprazole at high therapeutic doses does not affect the absorption and disposition of theophylline. PMID:10510158

  15. Effects of Theophylline on Anesthetized Malignant Hyperthermia-Susceptible Pigs

    Directory of Open Access Journals (Sweden)

    Marko Fiege

    2011-01-01

    Full Text Available Background. Theophylline was shown to induce contracture development in porcine malignant hyperthermia (MH susceptible (MHS skeletal muscles in vitro. The purpose of the current study was to investigate the in vivo effects of theophylline in MHS and MH normal (MHN swine. Methods. MH-trigger-free general anesthesia was performed in MHS and MHN swine. Theophylline was administered intravenously in cumulative doses up to 93.5 mg⋅kg-1. The clinical occurrence of MH was defined by changes of central-venous pCO2, central-venous pH, and body core temperature. Results. Theophylline induced comparable clinical alterations in the anesthetized MHS and MHN swine, especially in regard to hemodynamic data. No pig developed hypermetabolism and/or MH according to defined criteria. All animals died with tachycardia followed by ventricular fibrillation. Conclusions. The cumulative theophylline doses used in this study were much higher than doses used therapeutically in humans, as demonstrated by measured blood concentrations. Theophylline is thus not a trigger of MH in genetically determined swine.

  16. Acute theophylline exposure modulates breathing activity through a cervical contusion.

    Science.gov (United States)

    Hoy, Kevin C; Alilain, Warren J

    2015-09-01

    Cervical spinal contusion injuries are the most common form of spinal cord injury (>50%) observed in humans. These injuries can result in the impaired ability to breathe. In this study we examine the role of theophylline in the rescue of breathing behavior after a cervical spinal contusion. Previous research in the C2 hemisection model has shown that acute administration of theophylline can rescue phrenic nerve activity and diaphragmatic EMG on the side ipsilateral to injury. However, this effect is dependent on intact and uninjured pathways. In this study we utilized a cervical contusion injury model that more closely mimics the human condition. This injury model can determine the effectiveness of therapeutic interventions, in this case theophylline, on the isolated contused pathways of the spinal cord. Three weeks after a 150 kD C3/4 unilateral contusion subjects received a 15 mg/kg dose of theophylline prior to a contralateral C2 hemisection. Subjects that received theophylline were able to effectively utilize damaged pathways to breathe for up to 2 min, while subjects treated with saline were unable to support ventilation. Through these experiments, we demonstrate that theophylline can make injured pathways that mediate breathing more effective and therefore, suggest a potential therapeutic role in the critical time points immediately after injury. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Urinary excretion of methylated purines in man and in the rat after the administration of theophylline

    NARCIS (Netherlands)

    Gennip, A.H. van; Grift, J.; Bree-Blom, E.J. van; Ketting, D.; Wadman, S.K.

    1979-01-01

    Chromatographic characteristics of urinary metabolites of theophylline were studied by two-dimensional thin-layer chromatography, high-performance liquid chromatography and gas chromatography—mass spectrometry. Quantitative data for the urinary metabolites of theophylline in asthmatic children are

  18. Effects of Theophylline on Chronic Inflammatory Lung Injury Induced by LPS Exposure in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Yoshio Kaneko

    2007-01-01

    Conclusions: Theophylline improved airway injury as well as airway hyperreactivity induced by repetitive exposure of the guinea pigs to LPS. These results suggest that theophylline treatment has ameliorative effects on airway disease with chronic inflammation.

  19. Effect of theophylline on ventilator-induced diaphragmatic dysfunction.

    Science.gov (United States)

    Kim, Won-Young; Park, So Hee; Kim, Won Young; Huh, Jin Won; Hong, Sang-Bum; Koh, Younsuck; Lim, Chae-Man

    2016-06-01

    To evaluate the effect of theophylline in patients with ventilator-induced diaphragmatic dysfunction (VIDD). Patients who required mechanical ventilation at least 72 hours, met the criteria for a spontaneous breathing trial, and had evidence of VIDD by ultrasonography were included in the study. Of the 40 patients, 21 received theophylline and 19 did not. Clinical characteristics were similar in the 2 groups. Assessment of VIDD showed no between-group differences in baseline diaphragmatic excursion (DE) of both hemidiaphragms. Changes in DE from baseline to 72 hours (ΔDE) were significantly higher in the theophylline group than in the nontheophylline group in the right (3.5 ± 4.5 mm vs 0.4 ± 2.1 mm; P = .004) and left (3.2 ± 5.1 mm vs 0.1 ± 4.0 mm; P = .03) hemidiaphragms and in the total DE of both diaphragms (6.9 ± 9.1 mm vs 0.5 ± 5.7 mm; P = .02). In the theophylline group, theophylline was effective for the diaphragms with VIDD, whereas it was not effective for the diaphragms without VIDD. ΔDE in the right (rs = -0.49, P = .006) hemidiaphragm and total Δ DE in both diaphragms (rs = -0.46, P = .01) correlated negatively with weaning time. Theophylline significantly improved diaphragmatic movements in patients with VIDD. Our results warrant a larger study to determine whether theophylline use has benefits during weaning from mechanical ventilation. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Use of dika fat in the formulation of sustained release theophylline ...

    African Journals Online (AJOL)

    Sustained release theophylline tablets and capsules were prepared with dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonesis var gabonesis and var excelsia. Anhydrous theophylline was incorporated into dika fat by the fusion method. The in vitro release of the theophylline was monitored by the ...

  1. Quantification of theophylline-induced eosinopenia and hypokalaemia in healthy volunteers

    NARCIS (Netherlands)

    Braat, M. C.; Jonkers, R. E.; Bel, E. H.; van Boxtel, C. J.

    1992-01-01

    The relationship between theophylline pharmacokinetics and its eosinopenic and hypokalaemic effects were studied in 6 healthy volunteers after an oral dose of theophylline 250 mg. The mean peak theophylline concentration (Cmax) of 8.33 +/- 2.16 mg/L occurred 1.02 +/- 0.26 h after ingestion. The

  2. Low-dose theophylline reduces symptoms of acute mountain sickness.

    Science.gov (United States)

    Küpper, Thomas E A H; Strohl, Kingman P; Hoefer, Markus; Gieseler, Ulf; Netzer, Cordula M; Netzer, Nikolaus C

    2008-01-01

    Headache, nausea, and sleeplessness at altitude [acute mountain sickness (AMS)] are major health problems for several million mountain recreationists who ascend to high altitudes each year. We aimed to test the efficacy of low-dose, slow-release theophylline for the prevention of AMS in a placebo-controlled, double-blind, randomized trial. Twenty healthy male volunteers (mean age 34.7 y) were randomized (random allocation) to receive either 300 mg theophylline daily or placebo 5 days prior, during ascent, and during a stay at 4,559 m altitude. AMS symptoms were collected using the Lake Louise Score on each day during ascent and at high altitude. A 12-channel sleep recorder recorded sleep and breathing parameters during the first night at 4,559 m. Theophylline serum levels were drawn prior to the sleep study. Seventeen completed the entire study. Theophylline (n = 9) compared to placebo (n = 8) significantly reduced AMS symptoms at 4,559 m (Lake Louise Score: 1.5 +/- 0.5 vs placebo 2.3 +/- 2.37; p adverse drug effects were reported. Low-dose, slow-release theophylline reduces symptoms of AMS in association with alleviation of events of periodic breathing and oxygen desaturations.

  3. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline.

    Science.gov (United States)

    Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

    2006-08-24

    Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced through the use of this novel drug delivery

  4. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

    Directory of Open Access Journals (Sweden)

    Mohapatra Shyam S

    2006-08-01

    Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

  5. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

    Science.gov (United States)

    Lee, Dong-Won; Shirley, Shawna A; Lockey, Richard F; Mohapatra, Shyam S

    2006-01-01

    Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs) can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA) and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL) fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in treating asthma may be enhanced

  6. Thermochemical parameters of caffeine, theophylline, and xanthine

    Energy Technology Data Exchange (ETDEWEB)

    Ngo Tuan Cuong; Truong Ba Tai [Department of Chemistry, and Mathematical Modeling and Computational Science Center (LMCC), Katholieke Universiteit Leuven, B-3001 Leuven (Belgium); Vu Thi Thu Ha [Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi (Viet Nam); Minh Tho Nguyen, E-mail: minh.nguyen@chem.kuleuven.b [Department of Chemistry, and Mathematical Modeling and Computational Science Center (LMCC), Katholieke Universiteit Leuven, B-3001 Leuven (Belgium)

    2010-04-15

    Thermochemical parameters of caffeine 1, theophylline 2, xanthine 3, uracil, and imidazole derivatives are determined by quantum chemical calculations. Using the composite G3B3 method, the standard heat of formation of caffeine in the gaseous phase amounts to DELTA{sub f}H{sub g}{sup 0}(1)=-243+-8kJ.mol{sup -1}, which lends a support for the recent experimental value of -237.0 +- 2.5 kcal . mol{sup -1}. We also obtain DELTA{sub f}H{sub g}{sup 0}(2)=-232+-8kJ.mol{sup -1}andDELTA{sub f}H{sub g}{sup 0}(3)=-209+-8kJ.mol{sup -1}. The adiabatic ionization energies are IE{sub a}(1) = 7.9 eV, IE{sub a}(2) = 8.1 eV, and IE{sub a}(3) = 8.5 eV using B3LYP calculations. The enhanced ability of caffeine to eject electron, as compared to the parent compounds and cyclic components, is of interest with regard to its potential use as a corrosion inhibitor.

  7. Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients

    DEFF Research Database (Denmark)

    Hvidberg, A; Rasmussen, M H; Christensen, N J

    1994-01-01

    The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery......). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma...

  8. Effects of oral theophylline and oral salbutamol in the treatment of asthma.

    Science.gov (United States)

    Dawson, K P; Fergusson, D M

    1982-01-01

    A double-blind randomised controlled trial was conducted to study the effects of oral theophylline alone compared with oral theophylline and salbutamol in a sample of asthmatic children. Each treatment was administered at maximum recommended dosage. Children treated with the theophylline and salbutamol combination had higher pulse rates, lower peak flow measurements, and depressed blood theophylline levels. These results suggest that when given at maximum oral dosage, theophylline and salbutamol in combination, tend to interact negatively producing tachycardia and reduced therapeutic function. PMID:6751238

  9. The challenging case of the theophylline-benzamide cocrystal.

    Science.gov (United States)

    Fischer, Franziska; Schmidt, Martin U; Greiser, Sebastian; Emmerling, Franziska

    2016-03-01

    Theophylline has been used as an active pharmaceutical ingredient (API) in the treatment of pulmonary diseases, but due to its low water solubility reveals very poor bioavailability. Based on its different hydrogen-bond donor and acceptor groups, theophylline is an ideal candidate for the formation of cocrystals. The crystal structure of the 1:1 benzamide cocrystal of theophylline, C7H8N4O2·C7H7NO, was determined from synchrotron X-ray powder diffraction data. The compound crystallizes in the tetragonal space group P41 with four independent molecules in the asymmetric unit. The molecules form a hunter's fence packing. The crystal structure was confirmed by dispersion-corrected DFT calculations. The possibility of salt formation was excluded by the results of Raman and (1)H solid-state NMR spectroscopic analyses.

  10. Plants to Polyelectrolytes: Theophylline Polymers and Their Microsphere Synthesis.

    Science.gov (United States)

    Guterman, Ryan; Antonietti, Markus; Yuan, Jiayin

    2017-04-01

    To extend fossil oil supplies, sustainable feed stocks for the production of useful reagents and polymers should be harnessed. In this regard, chemicals derived from plants are excellent candidates. While the vast majority of plant sources used for polymer science only contain C x H y O z , alkaloids such as caffeine, nicotine, and theophylline possess nitrogen functionality that can provide new functions for bioderived polymers and their synthesis. In this context, the chemistry of theophylline, a natural product found in chocolate and tea, is exploited to create a cationic "poly(theophylline)" in a straightforward fashion for the first time. This work demonstrates how this new polymer can be synthesized and used for the creation of narrowly disperse cationic microspheres. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Severe theophylline poisoning treated with continuous venovenous hemodialysis in a child.

    Science.gov (United States)

    Yaman, Ayhan; Kendirli, Tanıl; Ödek, Çağlar; Azapağası, Ebru; Erkol, Hatice; Pişkin, İbrahim Etem; Teber-Tıraş, Serap; Yalçınkaya, Fatoş

    2016-01-01

    Theophylline poisoning generally occurs due to acute high dose intake as well as chronic intake of the medication. Toxicity symptoms can be seen with a plasma concentration of theophylline over 20 μg/ml. The consequences of theophylline toxicity include metabolic disturbances (hypokalemia, hyperglycemia, and metabolic acidosis), nausea, vomiting, and in severe cases seizures, cardiac arrhythmias, and death. Theophylline poisoning in children is rarely described in the literature. A 3-year-old girl was referred from another hospital to our pediatric intensive care unit (PICU) due to prolonged refractory status epilepticus and respiratory failure linked with severe theophylline poisoning. The patient was admitted to our PICU 24 hours after the patient took theophylline. The referring center could not measure the serum theophylline level. The patient's first serum theophylline level that was checked at admission was 54 μg/ml. We started continuous venovenous hemodialysis (CVVHD) 3 hours after PICU admission and the patient's theophylline level successfully decreased within 9 hours. The patient was discharged at the 40th day of admission from our hospital with severe neurological disability. In conclusion, severe theophylline poisoning may be seen in children. We must consider CVVHD in critically ill children with severe theophylline poisoning.

  12. Clinical pharmacology of theophylline in preterm infants: effects, metabolism and pharmacokinetics.

    Science.gov (United States)

    Pacifici, Gian Maria

    2014-01-01

    Recurrent apnea is common in preterm infants with consequent episodes of loss of effective breathing and the bronchodilator theophylline prevents apnea and reduces the number of apneic attacks. This drug also reduces hypoxaemic episodes. Theophylline acts on the lungs, kidneys and brain. Theophylline inhibits solute reabsorption in various segments of the nephron and a marked diuresis which occurs immediately after the administration of theophylline. This drug ameliorates kidney dysfunction and prophylaxis given early after birth, preventing vasomotor nephropathy. Theophylline reduces brain activity and reduces the spontaneous activity transients and alters the sleep-wake state in pre-term infants. Theophylline is extensively metabolized in premature infants and its major metabolic product is caffeine. The demethylation pathway occurring predominantly in adults is substituted by N-methylation to caffeine in premature infants. The halflife of theophylline is 5-fold longer in neonates than in adults and reaches the adult value at the age of 55 weeks. Theophylline may be administered trans-cutaneously by applying this drug to the back or abdomen of the infants and the mean fractional absorbance at 30 hours is 0.25. Theophylline is present in saliva and the concentration of this drug in saliva is similar to that in plasma, saliva may be used to monitor theophylline concentration. In conclusion, theophylline is a useful drug to treat apnea and ameliorate kidney dysfunction.

  13. Caffeine versus theophylline for apnea in preterm infants.

    Science.gov (United States)

    Henderson-Smart, David J; Steer, Peter A

    2010-01-20

    Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia, which may be severe enough to require resuscitation including use of positive pressure ventilation. Two forms of methylxanthine (caffeine and theophylline) have been used to stimulate breathing in order to prevent apnea and its consequences. To evaluate the effect of caffeine compared with theophylline treatment on the risk of apnea and use of mechanical ventilation in preterm infants with recurrent apnea. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases in August 2009: Oxford Database of Perinatal Trials; Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2009); MEDLINE (1966 to April 2009); and EMBASE Drugs and Pharmacology (1990 to April 2009), previous reviews including cross references. Randomized and quasi-randomized trials comparing caffeine to theophylline for treating apnea in preterm infants and reporting effects on apnea event rates. Each author assessed eligibility and trial quality, extracted data separately and compared and resolved differences. Study authors were contacted for additional information. Five trials involving a total of 108 infants were included. The quality of most of these small trials was fair to good. No difference in treatment failure rate (less than 50% reduction in apnea/bradycardia) was found between caffeine and theophylline after one to three days treatment (based on two studies) or five to seven days treatment (based on one study). There was no difference in mean apnea rate between caffeine and theophylline groups after one to three days treatment (based on five trials) and five to seven days treatment (based on four trials).Adverse effects, indicated by tachycardia or feed intolerance leading to change in dosing, were lower in the caffeine

  14. Synthesis and hypoglycemic activity of some new theophylline derivatives.

    Science.gov (United States)

    Alafeefy, Ahmed M; Alqasoumi, Saleh I; Abdel Hamid, Sami G; El-Tahir, Kamal E H; Mohamed, Menshawy; Zain, Mohamed E; Awaad, Amani S

    2014-06-01

    Thirty-one new theophylline derivatives have been synthesized and evaluated for their hypoglycemic activity. Compounds 24 (56% reduction) and 31 (57% reduction) showed better hypoglycemic activity than the standard drug glibenclamide which showed 52% reduction in serum glucose level. Compound 27 remarkably reduced serum glucose level by 53%. Ten compounds showed varying degrees of hypoglycemic activity ranging from 20 to 37% reduction in serum glucose level compared to the standard drug. The aromatic amide functionality is the common feature of these theophylline hypoglycemic derivatives. However, anthranilamide and or aliphatic amides proved to be the least active compounds in the present series.

  15. Transmission electron microscopy of a model crystalline organic, theophylline

    Science.gov (United States)

    Cattle, J.; S'ari, M.; Hondow, N.; Abellán, P.; Brown, A. P.; Brydson, R. M. D.

    2015-10-01

    We report on the use of transmission electron microscopy (TEM) to analyse the diffraction patterns of the model crystalline organic theophylline to investigate beam damage in relation to changing accelerating voltage, sample temperature and TEM grid support films. We find that samples deposited on graphene film grids have the longest lifetimes when also held at -190 °C and imaged at 200 kV accelerating voltage. Finally, atomic lattice images are obtained in bright field STEM by working close to the estimated critical electron dose for theophylline.

  16. Monitoring Theophylline Concentrations in Saline Using Terahertz ATR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Kei Takeya

    2016-03-01

    Full Text Available To assess the possibility of terahertz technology for the determination of drug concentration in blood, we endeavored to apply a terahertz (THz attenuated total reflection (ATR method to measure the levels of theophylline in saline. A change in reflected THz wave amplitude was observed in a theophylline concentration-dependent manner. This result was obtained with simple measurements of comparisons of the amplitude of the reflected wave, and suggests that it is possible to monitor concentration changes of drugs in liquid material using THz ATR measurements.

  17. Poly(acrylic acid) to induce competitive crystallization of a theophylline/oxalic acid cocrystal and a theophylline polymorph

    Science.gov (United States)

    Jang, Jisun; Kim, Il Won

    2016-01-01

    Polymeric additives to induce competitive crystallization of pharmaceutical compounds were explored. A cocrystal of theophylline and oxalic acid was used as a model system, and poly(acrylic acid), poly(caprolactone), and poly(ethylene glycol) were the additives. The cocrystal formation was selectively hindered with addition of poly(acrylic acid). First the size of the cocrystals were reduced, and eventually the cocrystallization was inhibited to generate neat theophylline crystals. The theophylline crystals were of a distinctively different crystal structure from known polymorphs, based on powder X-ray diffraction. They were also obtained in nanoscale size, when millimeter-scale crystals formed without poly(acrylic acid). Polymeric additives that could form specific interactions with crystallizing compounds seem to be useful tools for the phase and size control of pharmaceutical crystals.

  18. Partial agonism of theophylline-7-riboside on adenosine receptors

    NARCIS (Netherlands)

    IJzerman, A. P.; van der Wenden, E. M.; von Frijtag Drabbe Künzel, J. K.; Mathôt, R. A.; Danhof, M.; Borea, P. A.; Varani, K.

    1994-01-01

    Theophylline-7-riboside was evaluated as a partial agonist for rat adenosine receptors. Radioligand binding experiments were performed on both A1 and A2a adenosine receptors, using several methodologies to discriminate between agonists and antagonists. Mainly from thermodynamic data it was concluded

  19. Interaction of Ketotifen Fumarate with Anhydrous Theophylline in ...

    African Journals Online (AJOL)

    HP

    pH of main extracellular body fluids such as serum and lymph). The values of the stability constant, which varied between 5.07 and 6.35, indicate not only that complexation occured between ketotifen and theophylline but also that the interaction ...

  20. Pharmacokinetics of an extended-release theophylline product in cats.

    Science.gov (United States)

    Guenther-Yenke, Christine L; McKiernan, Brendan C; Papich, Mark G; Powell, Elizabeth

    2007-09-15

    To evaluate the pharmacokinetics of a brand of extended-release theophylline tablets and capsules in healthy cats. Randomized 3-way crossover study. 6 healthy cats. A single dose of aminophylline (10 mg/kg [4.5 mg/lb], IV), a 100-mg extended-release theophylline tablet, or a 125-mg extended-release theophylline capsule was administered to all cats. Plasma samples were collected via preplaced central catheters throughout a 36-hour period. Plasma samples were frozen until analyzed by use of a fluorescence polarization monoclonal immunoassay. All cats tolerated drug administration and plasma collection with no adverse effects. Peak concentrations were reached for both orally administered products between 8 and 12 hours after administration. Bioavailability was excellent. Plasma concentrations were within the human therapeutic concentration of 5 to 20 microg/mL. Daily administration of the brand of theophylline tablets and capsules used in this study at 15 mg/kg (6.8 mg/lb) and 19 mg/kg (8.6 mg/lb), respectively, maintained plasma concentrations within the desired therapeutic range in healthy cats.

  1. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    To examine the effects of once-daily, sustained- release theophylline on sleep patterns in nocturnal asthmatics. Design. Double-blind, randomised, cross-over, placebo- controlled trial ... 22-day trial, 3 patients having withdrawn due to adverse events. During the initial 7 days of the stUdy, serum was obtained at 07hOO and ...

  2. 21 CFR 862.3880 - Theophylline test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Theophylline test system. 862.3880 Section 862.3880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862...

  3. Voltammetric determination of theophylline at a Nafion/multi-wall ...

    Indian Academy of Sciences (India)

    A Nafion/multi-wall carbon nanotubes (MWNTs) composite film-modified electrode was fabricated and applied to the sensitive and convenient determination of theophylline (TP). Multi-wall carbon nanotubes (MWNTs) were easily dispersed homogeneously into 0.1% Nafion methanol solution by sonication. Appropriate ...

  4. Voltammetric determination of theophylline at a Nafion/multi-wall ...

    Indian Academy of Sciences (India)

    Administrator

    Abstract. A Nafion/multi-wall carbon nanotubes (MWNTs) composite film-modified electrode was fabricated and applied to the sensitive and convenient determination of theophylline (TP). Multi-wall carbon nanotubes (MWNTs) were easily dispersed homogeneously into 0.1% Nafion methanol solution by sonication.

  5. Intravenous theophylline rapidly decreases post-lumbar puncture headaches.

    Science.gov (United States)

    Ergün, Ufuk; Ünal-Artık, H Aybüke; İnan, Leven E; Yoldaş, Tahir

    2016-09-01

    When managing therapy for the post-lumbar puncture headaches (PLPHs), an efficacious, fast-acting, practical and safe method is preferred. Invasive methods have known complications and oral medications might be problematic when nausea and vomiting occurs with severe headaches. The aim of this study was to highlight the brief initial time for a remarkable decrease of PLPH pain levels after the administration of IV theophylline infusion. We observed that IV theophylline infusion has a rapid and marked effect on decreasing pain in PLPHs. At 30 min of theophylline infusion, mean VAS levels were decreased by 47.1 % and at 60 min of infusion, the decrease of pain was 61.9 %. We conclude that IV theophylline infusion is a rapidly effective, noninvasive, practical and low-cost way to treat PLPHs. To the best of our knowledge, this is the first study to highlight both the efficacy and the speed of the effect of pain relief in PLPHs.

  6. Theophylline improves lipopolysaccharide-induced alveolarization arrest through inflammatory regulation.

    Science.gov (United States)

    He, Hua; Chen, Fei; Ni, Wensi; Li, Jianhui; Zhang, Yongjun

    2014-07-01

    Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased numbers of alveoli and increased airspace. BPD, frequently suffered by very low birth weight infants, has been closely associated with intrauterine infection. However, the underlying mechanisms of BPD remain unclear. In the present study, it was identified that administration of intra-amniotic lipopolysaccharide (LPS) to pregnant rats on embryonal day 16.5 (E16.5) induced significant alveolarization arrest similar to that of BPD in neonatal pups, and theophylline injected subcutaneously into the newborns improved the pathological changes. To further investigate the underlying mechanism of the morphogenesis amelioration of theophylline, cytokine antibody arrays were performed with the lung lysates of neonatal rats. The results indicated that LPS upregulated a series of pro-inflammatory cytokines and theophylline significantly attenuated the expression levels of pro-inflammatory cytokines tumor necrosis factor‑α, macrophage inflammatory protein (MIP)-1α and MIP-2, and markedly elevated the production of tumor growth factor (TGF)-β family members TGF-β1, TGF-β2 and TGF-β3, which are anti‑inflammatory cytokines. Accordingly, it was hypothesized that theophylline may protect against BPD and improve chorioamnionitis‑induced alveolar arrest by regulating the balance between pro‑and anti-inflammatory cytokine expression.

  7. The "shrinking lung syndrome" in SLE, treatment with theophylline

    NARCIS (Netherlands)

    van Veen, S.; Peeters, A. J.; Sterk, P. J.; Breedveld, F. C.

    1993-01-01

    We report on a patient with systemic lupus erythematosus who developed a shrinking lung syndrome. The dyspnoea of the patient and the results of pulmonary function tests significantly improved during treatment with theophylline 750 mg daily. This is the first report of a successful treatment of the

  8. Methods of theophylline assay and therapeutic monitoring of this drug.

    Science.gov (United States)

    Mounié, J; Richard, L; Ribon, B; Hersant, J; Sarmini, H; Houin, G; Mouine, J

    1990-01-01

    The purpose of this article is to review various analytical methods of monitoring plasma theophylline. This article was investigated by the "Drug Commission" of SFBC (Société Française de Biologie Clinique). The primary objective is to provide the "know-how", particular for this analysis, which allows the choice between various analytical methods available: immunochemical or physiochemical ones. The techniques described are not necessarily the best, they are approved and tested methods which are the most frequently used in routine practice. The proposed immunochemical methods are: absorption spectroscopy methods: Enzyme ImmunoAssay (EIA), Enzyme Multiplied ImmunoAssay Technique (EMIT); Reflectance spectroscopy method: Apoenzyme Reactivation Immunoassay System (ARIS); Fluorometry spectroscopy method: Substrate Labeled FluoroImmunoAssay (SLFIA); Fluorometry spectroscopy on solid base; Polarization fluorescence spectroscopy ImmunoAssay (FPIA); Turbidimetric measurements: Particle Enhanced Turbidimetric Inhibition ImmunoAssay (PETINIA); Nephelometric measurement: Nephelometric Inhibition ImmunoAssay (NIIA). And the proposed physicochemical methods are: High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC). The second objective is a review of pharmacological properties of theophylline, necessary for a good understanding of therapeutic drug monitoring: intestinal resorption, distribution, metabolism and elimination, drug interactions, dose/response relationship, physiopathological variations and proposed "predictive" "theophylline test". The authors conclude that because of the multiplicity of methodologies used in theophylline therapeutic monitoring the choice of one of them is not easy. The best way to compare different techniques available would be the use of a "reference material" for theophylline monitoring and a quality control network between different clinical pharmacological laboratories.

  9. Serum theophylline concentrations during multiple dosing with two sustained release methylxanthine preparations in normal subjects.

    Science.gov (United States)

    Prior, J. G.; Berry, D.; Cochrane, G. M.

    1980-01-01

    In normal subjects, receiving multiple dosing regimens with Slophyllin and Phyllocontin in does calculated to give either 4 mg/kg or 6mg/kg theophylline free acid twice daily, serum theophylline concentrations were frequently less than 8 mg/l. Accumulation of the serum theophylline trough concentration occurred during the first 3 days of multiple dosing, and was followed by subsequent stabilization or even decline in serum theophylline trough concentrations. Side effects were noted with both Slophyllin and Phyllocontin, but only on the higher dosage regimens; they occurred within 24--48 hr of starting the drug, and tended to diminish if dosing was continued. The accumulation effect of serum theophylline concentrations may explain the timing of adverse effects, and should be avoided by starting methylxanthine therapy at a low dose. This may be increased after a few days. Further dosage adjustment may be necessary in some patients and should be facilitated by measurement of serum theophylline trough concentrations. PMID:7465472

  10. A Prospective Survey on Safety of Sustained-Release Theophylline in Treatment of Asthma and COPD

    Directory of Open Access Journals (Sweden)

    Sohei Makino

    2006-01-01

    Conclusions: The present survey demonstrates that sustained-release theophylline is safe, as long as used appropriately, although adverse reactions tend to develop early after initiation of administration.

  11. [Quantitative analysis of theophylline and its metabolites in urine of Chinese healthy subjects after oral administration of theophylline sustained-release tablets].

    Science.gov (United States)

    Liu, Ying; Zhan, Yan; Zhang, Yi-Fan; Chen, Xiao-Yan; Zhong, Da-Fang

    2014-07-01

    To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.

  12. Extracorporeal treatment for theophylline poisoning: systematic review and recommendations from the EXTRIP workgroup.

    Science.gov (United States)

    Ghannoum, Marc; Wiegand, Timothy J; Liu, Kathleen D; Calello, Diane P; Godin, Melanie; Lavergne, Valery; Gosselin, Sophie; Nolin, Thomas D; Hoffman, Robert S

    2015-05-01

    The Extracorporeal Treatments in Poisoning workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Here, the workgroup presents its systematic review and recommendations for theophylline. After a systematic review of the literature, a subgroup reviewed articles, extracted data, summarized findings, and proposed structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed. A second vote determined the final recommendations. 141 articles were included: 6 in vitro studies, 4 animal studies, 101 case reports/case series, 7 descriptive cohorts, 4 observational studies, and 19 pharmacokinetic studies, yielding a low-to-very-low quality of evidence for all recommendations. Data on 143 patients were reviewed, including 10 deaths. The workgroup concluded that theophylline is dialyzable (level of evidence = A) and made the following recommendations: ECTR is recommended in severe theophylline poisoning (1C). Specific recommendations for ECTR include a theophylline concentration [theophylline] > 100 mg/L (555 μmol/L) in acute exposure (1C), the presence of seizures (1D), life-threatening dysrhythmias (1D) or shock (1D), a rising [theophylline] despite optimal therapy (1D), and clinical deterioration despite optimal care (1D). In chronic poisoning, ECTR is suggested if [theophylline] > 60 mg/L (333 μmol/L) (2D) or if the [theophylline] > 50 mg/L (278 μmol/L) and the patient is either less than 6 months of age or older than 60 years of age (2D). ECTR is also suggested if gastrointestinal decontamination cannot be administered (2D). ECTR should be continued until clinical improvement is apparent or the [theophylline] is Theophylline poisoning is amenable to ECTRs. The workgroup recommended

  13. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Nielsen, M K; Eriksen, P B; Fenger, M

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... theophylline concentration....

  14. RNA binding efficacy of theophylline, theobromine and caffeine.

    Science.gov (United States)

    Johnson, I Maria; Kumar, S G Bhuvan; Malathi, R

    2003-04-01

    The binding of naturally occurring methylxanthines such as theophylline, theobromine and caffeine to nucleic acids are reckoned to be pivotal as they are able to modulate the cellular activities. We explore the interaction of yeast RNA binding efficacy of the above xanthine derivatives by using UV absorption differential spectroscopy and Fourier Transform Infrared (FTIR) spectroscopy. Both the analyses show discrimination in their binding affinity to RNA. The differential UV-spectrum at P/D 3.3 reveals the greater RNA binding activity for theophylline (85 +/- 5%), whereas moderate and comparatively less binding activity for theobromine (45 +/- 5%) and caffeine (30 +/- 5%) and the binding activity was found to depend on concentration of the drugs. In FTIR analysis we observed changes in the amino group (NH) of RNA complexed by drugs, where the NH band is found to become very broad, indicating hydrogen bonding (H-bonding) with theophylline (3343.4 cm(-1)), theobromine (3379.8 cm(-1)) and caffeine (3343 cm(-1)) as compared to the free RNA (3341.6 cm(-1)). Furthermore in RNA-theophylline complex, it is observed that the carbonyl (C=O) vibration frequency (nu(C=O)) of both drug (nu(C=O)=1718, 1666 cm(-1)) as well as RNA (nu(C=O)=1699, 1658 cm(-1)) disappeared and a new vibration band appeared around 1703 cm(-1), indicating that the C=O and NH groups of drug and RNA are effectively involved in H-bonding. Whereas in RNA-theobromine and RNA-caffeine complexes, we found very little changes in C=O frequency and only broadening of the NH band of RNA due to complexation is observed in these groups. The changes in the vibrations of G-C/A-U bands and other bending frequencies are discussed. Thus the discrimination in the binding affinity of methylxanthines with RNA molecule shows that strong RNA binding drugs like theophylline can selectively be delivered to RNA targets of microbial pathogens having the mechanism of RNA catalysis.

  15. Theophylline toxicity leading to suicidal ideation in a patient with no prior psychiatric illness

    Directory of Open Access Journals (Sweden)

    Sumit Kapoor

    2015-04-01

    Full Text Available Suicidal behavior is a common psychiatric emergency and is associated with psychiatric illness and history of prior suicide attempts. Neuropsychiatric manifestations related to theophylline toxicity are well described in literature. We report a case of theophylline toxicity manifesting as suicidal ideation in a patient with no prior psychiatric illness.

  16. Comparison of gastroretentive microspheres and sustained-release preparations using theophylline pharmacokinetics.

    Science.gov (United States)

    Miyazaki, Yasunori; Yakou, Shigeru; Takayama, Kozo

    2008-06-01

    The objective of this study was to use the pharmacokinetics of theophylline to compare various gastroretentive microspheres. Three types of theophylline microspheres prepared from a hydrophobic dextran derivative were characterized in terms of drug release in-vitro and floating and mucoadhesive properties. Theophylline pharmacokinetic studies were conducted in Beagle dogs, comparing bulk powder, commercial sustained-release granules (Theodur), sustained-release microspheres, floatable microspheres and mucoadhesive microspheres. Theodur and sustained-release microspheres resulted in a lower maximum concentration (Cmax) (P mucoadhesive microspheres indicated an increase in AUC without decreasing the rate of bioavailability. Overall, the gastroretentive microspheres improved the extent of bioavailability of theophylline, which is absorbable from the entire gastrointestinal tract. The mucoadhesive microsphere showed a prolonged serum drug level, indicating a superior sustained-release delivery system for theophylline.

  17. Comparative study of the binding of trypsin to caffeine and theophylline by spectrofluorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruiyong, E-mail: wangry@zzu.edu.cn [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China); Kang, Xiaohui [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China); Wang, Ruiqiang [The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wang, Rui; Dou, Huanjing; Wu, Jing; Song, Chuanjun [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China); Chang, Junbiao, E-mail: changjunbiao@zzu.edu.cn [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China)

    2013-06-15

    The interactions between trypsin and caffeine/theophylline were investigated by fluorescence spectroscopy, UV–visible absorption spectroscopy, resonance light scattering and synchronous fluorescence spectroscopy under mimic physiological conditions. The results revealed that the fluorescence quenching of trypsin by caffeine and theophylline was the result of the formed complex of caffeine–trypsin and theophylline–trypsin. The binding constants and thermodynamic parameters at three different temperatures were obtained. The hydrophobic interaction was the predominant intermolecular forces to stabilize the complex. Results showed that caffeine was the stronger quencher and bound to trypsin with higher affinity than theophylline. -- Highlights: ► The fluorescence of trypsin can be quenched by caffeine or theophylline via hydrophobic contacts. ► Caffeine binds to trypsin with higher affinity than theophylline. ► The influence of molecular structure on the binding aspects is reported.

  18. Absence of Effect of Rufloxacin on Theophylline Pharmacokinetics in Steady State†

    Science.gov (United States)

    Kinzig-Schippers, Martina; Fuhr, Uwe; Cesana, Marina; Müller, Carola; Staib, A. Horst; Rietbrock, S.; Sörgel, Fritz

    1998-01-01

    Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1.02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events. PMID:9736563

  19. Reversal of acute theophylline toxicity by calcium channel blockers in dogs and rats.

    Science.gov (United States)

    Whitehurst, V E; Joseph, X; Vick, J A; Alleva, F R; Zhang, J; Balazs, T

    1996-06-17

    Theophylline, widely used in the treatment of pulmonary diseases, has a narrow therapeutic index; the recommended plasma levels being 10-20 micrograms/ml in humans. The misuse or abuse of theophylline can cause life-threatening central nervous system and cardiovascular effects. Increased intracellular Ca2+ levels are thought to play an important role in theophylline toxicity and death. The objective of this study was to determine whether Ca2+ channel blockers, e.g. verapamil, nifedipine, or diltiazem, prevent sudden death caused by theophylline treatment in rats and dogs. Groups of Sprague-Dawley rats were treated with theophylline alone (150 mg/kg i.p.) or with theophylline pretreatment followed by administration of verapamil (0.25 to 0.5 mg/kg i.p.), nifedipine (0.25 to 1.0 mg/kg i.p.), or diltiazem (0.5 to 1.0 mg/kg i.p.), 2.5 to 15 min later. The rats were observed for toxic signs and survival over a period of 15 days. All three calcium channel blockers significantly reduced the theophylline-induced sudden death in rats. In a separate study, neither verapamil (0.5 mg/kg i.p.) nor nifedipine (1.0 mg/kg i.p.) prevented the theophylline-induced myocardial necrosis in the rat. In beagle dogs, verapamil (0.5 mg/kg i.v.) prevented theophylline (15 mg/kg/min i.v. for 10 min)-induced hypotension, arrhythmias, and sudden death. Our results support previously reported findings that calcium plays a major role in theophylline-induced toxicity and death.

  20. Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs.

    Science.gov (United States)

    Al-Jenoobi, Fahad I; Ahad, Abdul; Mahrous, Gamal M; Al-Mohizea, Abdullah M; AlKharfy, Khalid M; Al-Suwayeh, Saleh A

    2015-02-01

    Herb-drug interactions are a serious problem especially for drugs with a narrow therapeutic index, taking into consideration that herbal medicines are commonly used in various parts of the world. The present study investigates the effect of fenugreek, garden cress, and black seed on the pharmacokinetics of theophylline in beagle dogs. Beagle dogs received theophylline (200 mg) orally and blood samples were withdrawn at different time intervals (0.33, 0.66, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, and 30 h). After a suitable washout period, each herb was given orally at doses of 25, 7.5, and 2.5 g, twice daily for 7 d. On the eighth day, theophylline was re-administrated orally and blood samples were collected. Plasma concentrations of theophylline were determined using HPLC and pharmacokinetic parameters were calculated using a non-compartmental analysis. Treatment with fenugreek (25 g, orally) lead to a decrease in Cmax and AUC0-t of theophylline of about 28% (p theophylline (2.10 ± 0.24 h versus 3.40 ± 0.74 h), while AUC0-∞ increased by 37.44%. No significant effect was observed for the black seed treatment on theophylline disposition as measured by Cmax, Tmax, AUC0-∞, and CL/F. The concurrent use of fenugreek or garden cress alters theophylline pharmacokinetic behavior in an animal model. This could represent a modulation in cytochrome P450 activity, which is responsible for theophylline metabolism in beagle dogs. Further confirmation of these results in humans will warrant changes in theophylline dosing before the co-administration of such herbs.

  1. Use of Bosentan, Theophylline and Vardenafil in Treatment of Priapism

    Directory of Open Access Journals (Sweden)

    Ihsan Unus

    2016-03-01

    Full Text Available Objective: To evaluate the early therapeutic alternatives such as Bosentan an Endothelin receptor blocker, The­ophylline and Adenosin receptor blocker and Vardenafil a non-selective Phosphodiesterase 5 enzyme inhibitor for the therapy of ischemic priapism in the rat models. Methods: Twenty-four Sprague-Dawley rats were ran­domly divided into 4 equal groups. Control group, Var­denafil group, Bosentan group and Theophylline group. Erection was provided by vacuum constriction method and it was maintained for 4 hours for achieving the pria­pism in all groups. Then, Six rats from each group were sacrificed by cervical dislocation. Consequently, cavern­ous tissue samples were collected and placed in the tis­sue bath. Tissue samples were prepared as 0.5-0.2 cm. strips and put into heat jacketed double walled organ bath containing 37°C krebs solution which is constantly bubbled with 95% O2 and 5 % CO2 and mounted at a resting tension of 1000 mg. After taking the 1 hour record of the three groups except the control group, Bosentan, Theophylline and Vardenafil were admitted in increasing doses. Consequently the alterations of the contractions in the strips due to the drugs and their increasing doses are observed. Results: In this study we detected that Bosentan in­creased the frequency and amplitude of the contractions of the cavernous tissue in the Priapism status in a sta­tistically significant manner, Theophylline decreased the frequency and the amplitude significantly and Vardenafil had statistically no effect on the frequency and amplitude. Conclusion: Inhibition of priapism induced apoptosis with Bosentan, seems promising on preserving erectile function.

  2. Temporal reduction in size of salivary acinus in rats induced by theophylline.

    Science.gov (United States)

    Kajikawa, Satoru; Takeuchi, Ayano; Nii, Aisuke; Nakayama, Hiroyuki; Doi, Kunio

    2005-01-01

    Repeated administration of theophylline, a phosphodiesterase inhibitor, induces the enlargement of the salivary glands in rats. Time-course changes after a single administration of theophylline were examined in the salivary glands, including phosphodiesterase enzyme activity, and the expression of aquaporin 5 (AQP5), a water channel. We also examined the contribution of beta-adrenergic receptors to theophylline-induced salivary changes. Male F344 rats were given 50 mg/kg of theophylline intraperitoneally either alone or concurrently with a 10 mg/kg subcutaneous injection of propranolol. After treatment with theophylline alone, the weight and histology of the submaxillary and parotid glands were examined. Phosphodiesterase activity and AQP5 were detected by enzyme- and immuno-histochemistry, respectively. At 4 hours, 8 hours, or both, organ weights were decreased with depletion of secretory vesicles in the acinar cells. In the submaxillary glands, reduced activity of phosphodiesterase and increased expression of AQP5 in the intercalated ducts were observed at 4 hours. When co-administered, propranolol partially abolished theophylline-induced glandular reduction. These results suggest that the theophylline-induced transient reduction in size of the salivary glands is attributable not only to phosphodiesterase inhibition but also to beta-adrenergic receptor activation and that the intercalated ducts in submaxillary glands play a role in the production of saliva.

  3. To study the efficacy and safety of doxophylline and theophylline in bronchial asthma.

    Science.gov (United States)

    Margay, Sami Manzoor; Farhat, Samina; Kaur, Sharanjit; Teli, Hilal Ahmad

    2015-04-01

    Asthma is a non communicable chronic disease prevalent all over the world. Two commonly used methylxanthines, theophylline and doxofylline were compared in the study in stable asthmatic patients at recommended doses by various spirometric lung function tests with forced expiratory volume at second one (FEVI) between 50 to 80% of predicted FEVI. A total of 100 patients were divided in two groups. Group I was administered 300 mg theophylline twice a day and Group II was administered doxofylline 400 mg twice a day orally for six weeks. Spirometric variables symptom score, and adverse effects were recorded at the baseline level and after six weeks of therapy. Data was compared and analysed statistically. The spirometric values of forced expiratory volume in 1 second (FEVI), forced vital capacity (FVC), and FEV1/FVC showed a statistically significant improvement over base line with the use of both theophylline as well as doxophylline, but were not statistically different from each other. There was a statistically significant improvement in peak expiratory flow rate (PEFR) after six weeks of treatment with doxophylline compared to theophylline. It was found that the doxophylline has a better safety profile as compared to theophylline. Adverse events occurred in a greater proportion of patients in the theophylline group. In the study it was concluded that both theophylline and doxofylline improved the lung function tests and symptoms in patients of mild Bronchial Asthma, but doxofylline has a better profile in terms of safety.

  4. The effect of theophylline on acetic acid induced ulcerative colitis in rats.

    Science.gov (United States)

    Ghasemi-Pirbaluti, Masoumeh; Motaghi, Ehsan; Najafi, Ali; Hosseini, Mohammad Javad

    2017-06-01

    Ulcerative colitis is a relapsing inflammatory disorder of the colon. There is a need to explore the new treatments for this disorder. Theophylline, a competitive inhibitor of phosphodiesterase, is shown to have anti-inflammatory properties. However, the effect of theophylline on ulcerative colitis has not yet been investigated. The present study evaluated the effect of theophylline on acetic acid induced ulcerative colitis in rats. Colitis was induced by instillation of 2ml of acetic acid solution (3%). Colon samples were evaluated grossly and microscopically and assayed for myeloperoxidase (MPO) activity and proinflammatory cytokine concentrations. Treatment with theophylline at the doses of 20 and 50mg/kg attenuated acetic acid induced ulcerative colitis as shown by improvement in body weight loss, macroscopic score, ulcer area, hematocrit and histopathological score. Theophylline treatment also reduced MPO activity and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1 β) and interleukin 6 (IL-6) concentrations in inflamed colon. Theophylline has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities. Therefore, theophylline has the potential to be used for successful treatment of ulcerative colitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Use of theophylline in chronic obstructive pulmonary disease: examining the evidence.

    Science.gov (United States)

    Ram, Felix S F

    2006-03-01

    The role of theophylline in the management of chronic obstructive pulmonary disease remains controversial. This review was undertaken to determine the efficacy of theophylline in patients with stable disease. Twenty-two good quality randomized controlled trials were included in this systematic review. The review showed that theophylline significantly improved forced expiratory volume in 1 s and forced vital capacity (weighted mean difference 0.10 L; 95% confidence interval 0.04-0.16 and weighted mean difference 0.21 L; 95% confidence interval 0.10-0.31, respectively). V also improved with theophylline (weighted mean difference 195.27 mL/min; 95% confidence interval 112.71-277.83), as did Pa and Pa (weighted mean difference 1.45 mmHg; 95% confidence interval 0.26-2.65 and weighted mean difference -1.09 mmHg; 95% confidence interval -1.83 to -0.35, respectively). Patients preferred theophylline over placebo (relative risk 2.27; 95% confidence interval 1.26-4.11). Theophylline increased the risk of nausea, however, compared with placebo (relative risk 7.67; 95% confidence interval 1.47-39.94). This review has shown that oral theophylline plays an important role in the management of patients with stable chronic obstructive pulmonary disease by improving lung function, arterial blood gas tensions and ventilatory capacity. Patients also preferred treatment with theophylline when compared with placebo. The benefits of theophylline in stable chronic obstructive pulmonary disease, however, have to be weighed against the risk of adverse effects, particularly nausea.

  6. Theophylline attenuates Ca2+ sensitivity and modulates BK channels in porcine tracheal smooth muscle

    Science.gov (United States)

    Ise, Shinji; Nishimura, Junji; Hirano, Katsuya; Hara, Nobuyuki; Kanaide, Hideo

    2003-01-01

    Theophylline, a nonselective phosphodiesterase inhibitor, has long been regarded as a major bronchodilator in the treatment of human asthma. Using front-surface fluorometry with fura-2 and α-toxin permeabilization, the effects of theophylline on intracellular Ca2+ concentration ([Ca2+]i), tension development and Ca2+ sensitivity of the contractile apparatus were investigated in porcine tracheal smooth muscle strips. Application of theophylline induced a relaxation without a significant decrease in [Ca2+]i when strips were precontracted by 40 mM K+ depolarization, while theophylline significantly decreased both [Ca2+]i and tension induced by carbachol. The effects of theophylline on the increases in [Ca2+]i and tension induced by carbachol were significantly inhibited by iberiotoxin, an inhibitor of large-conductance Ca2+-activated K+ channels. In the absence of extracellular Ca2+, theophylline significantly attenuated carbachol-induced transient increases in tension development, while it did not affect carbachol-induced transient increase in [Ca2+]i. The [Ca2+]i–force relationship, which was determined by cumulative applications of extracellular Ca2+ (0–5 mM) during 40 mM K+ depolarization, was significantly shifted to the right by theophylline. In α-toxin permeabilized strips, theophylline significantly increased the EC50 value of [Ca2+]i for contraction and enhanced the effect of cAMP, but not of cGMP. These results indicate that theophylline induces relaxation of the porcine tracheal smooth muscle through an activation of BK channels, and a resultant decrease in [Ca2+]i and an attenuation of Ca2+ sensitivity, presumably through the action of cAMP. PMID:14517178

  7. Theophylline inhibits the cough reflex through a novel mechanism of action.

    Science.gov (United States)

    Dubuis, Eric; Wortley, Michael A; Grace, Megan S; Maher, Sarah A; Adcock, John J; Birrell, Mark A; Belvisi, Maria G

    2014-06-01

    Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds. We sought to investigate the inhibitory activity of theophylline on vagal sensory nerve activity and the cough reflex. Using a range of techniques, we investigated the effect of theophylline on human and guinea pig vagal sensory nerve activity in vitro and on the cough reflex in guinea pig challenge models. Theophylline was antitussive in a guinea pig model, inhibited activation of single C-fiber afferents in vivo and depolarization of human and guinea pig vagus in vitro, and inhibited calcium influx in airway-specific neurons in vitro. A sequence of pharmacological studies on the isolated vagus and patch clamp and single-channel inside-out experiments showed that the effect of theophylline was due to an increase in the open probability of calcium-activated potassium channels. Finally, we demonstrated the antitussive activity of theophylline in a cigarette smoke exposure model that exhibited enhanced tussive responses to capsaicin. Theophylline inhibits capsaicin-induced cough under both normal and "disease" conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. These findings could lead to the development of optimized antitussive compounds with a reduced side effect potential. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  8. Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity.

    Science.gov (United States)

    Fisher, Julia; Graudins, Andis

    2015-09-01

    Theophylline overdose can result in significant cardiovascular and neurologic toxicity and is potentially fatal. Clearance of theophylline can be enhanced by the administration of multiple-dose activated charcoal (MDAC) and extracorporeal elimination techniques. We report a case of severe theophylline toxicity initially treated with MDAC and intermittent haemodialysis. Subsequent to this, sustained low-efficiency dialysis (SLED) was undertaken. This is a prolonged renal replacement therapy that uses blood and dialysate flow rates between those of intermittent haemodialysis and continuous renal replacement therapy. A 61-year-old man presented following ingestion of 24 g of theophylline SR (300 mg/kg), 240 mg of diazepam and 2 g of gabapentin. He required intubation and developed a supraventricular tachycardia treated with esmolol, but suffered no seizures. Serum theophylline concentration peaked at 636 μmol/L (55-110) at 9.5 h post-ingestion. Intermittent haemodialysis was performed for 4 h and resulted in a theophylline extraction ratio of 0.57 with elimination half-life of 2.3 h. SLED was subsequently performed on two occasions for 7 h. Theophylline extraction ratio ranged from 0.46 (half-life 5.3 h during the first cycle) to 0.61 (half-life 10.6 h during the second cycle). After cessation of SLED, elimination half-life was 26 h. The patient made an uneventful recovery. Intermittent haemodialysis is the current recommended extracorporeal technique for enhancing theophylline elimination in the absence of charcoal haemoperfusion. However, SLED produced similar apparent extraction ratios with longer associated elimination half-life for theophylline than for intermittent haemodialysis. SLED is undertaken by intensive care unit (ICU) staff and may be a useful extracorporeal elimination technique in cases where access to intermittent haemodialysis, requiring specialist dialysis nursing staff, is limited or may be delayed.

  9. Theophylline inhibits the cough reflex through a novel mechanism of action☆

    Science.gov (United States)

    Dubuis, Eric; Wortley, Michael A.; Grace, Megan S.; Maher, Sarah A.; Adcock, John J.; Birrell, Mark A.; Belvisi, Maria G.

    2014-01-01

    Background Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds. Objective We sought to investigate the inhibitory activity of theophylline on vagal sensory nerve activity and the cough reflex. Methods Using a range of techniques, we investigated the effect of theophylline on human and guinea pig vagal sensory nerve activity in vitro and on the cough reflex in guinea pig challenge models. Results Theophylline was antitussive in a guinea pig model, inhibited activation of single C-fiber afferents in vivo and depolarization of human and guinea pig vagus in vitro, and inhibited calcium influx in airway-specific neurons in vitro. A sequence of pharmacological studies on the isolated vagus and patch clamp and single-channel inside-out experiments showed that the effect of theophylline was due to an increase in the open probability of calcium-activated potassium channels. Finally, we demonstrated the antitussive activity of theophylline in a cigarette smoke exposure model that exhibited enhanced tussive responses to capsaicin. Conclusion Theophylline inhibits capsaicin-induced cough under both normal and “disease” conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. These findings could lead to the development of optimized antitussive compounds with a reduced side effect potential. PMID:24406072

  10. Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation

    Science.gov (United States)

    Yao, Pei-Li; Tsai, Meng-Feng; Lin, Yi-Chen; Wang, Chien-Hsun; Liao, Wei-Yu; Chen, Jeremy JW; Yang, Pan-Chyr

    2005-01-01

    Background Theophylline has been used widely as a bronchodilator for the treatment of bronchial asthma and has been suggested to modulate immune response. While the importance of macrophages in asthma has been reappraised and emphasized, their significance has not been well investigated. We conducted a genome-wide profiling of the gene expressions of macrophages in response to theophylline. Methods Microarray technology was used to profile the gene expression patterns of macrophages modulated by theophylline. Northern blot and real-time quantitative RT-PCR were also used to validate the microarray data, while Western blot and ELISA were used to measure the levels of IL-13 and LTC4. Results We identified dozens of genes in macrophages that were dose-dependently down- or up-regulated by theophylline. These included genes related to inflammation, cytokines, signaling transduction, cell adhesion and motility, cell cycle regulators, and metabolism. We observed that IL-13, a central mediator of airway inflammation, was dramatically suppressed by theophylline. Real-time quantitative RT-PCR and ELISA analyses also confirmed these results, without respect to PMA-treated THP-1 cells or isolated human alveolar macrophages. Theophylline, rolipram, etazolate, db-cAMP and forskolin suppressed both IL-13 mRNA expression (~25%, 2.73%, 8.12%, 5.28%, and 18.41%, respectively) and protein secretion (theophylline may be through cAMP mediation and may decrease LTC4 production. This study supports the role of theophylline as a signal regulator of inflammation, and that down regulation of IL-13 by theophylline may have beneficial effects in inflammatory airway diseases. PMID:16083514

  11. Influences of Pyrexia and Age on Theophylline Clearance in Young Children with Asthma

    OpenAIRE

    Imai, Keisuke; Munehisa, Yumiko; Yoshikuni, Yoshiko; Morita, Tadayuki; Nomura, Hiroaki; Kimura, Yasuhiro; Mimaki, Yuichi; Kihira, Kenji

    2012-01-01

    Fifty hospitalized children with asthmatic bronchitis and bronchial asthma were treated with a continuous intravenous drip infusion of aminophylline. To investigate the pharmacokinetics of theophylline in the presence of pyrexia, patients were divided into two groups based on body temperature: a pyrexia group (≥ 38°C) and a non-pyrexia group (< 38°C). Theophylline clearance was 0.064 ± 0.017 liters/kg/hr in the non-pyrexia group and 0.049 ± 0.010 liters/kg/hr in the pyrexia group. Theophyllin...

  12. Effect of drug-polymer interaction on the release characteristics of methacrylic acid copolymer microcapsules containing theophylline.

    Science.gov (United States)

    Hsiue, G H; Liao, C M; Lin, S Y

    1998-08-01

    Theophylline anhydrate microcapsules with different amounts of MA/MMA copolymer (Eudragit L) were prepared by the solvent evaporation method. Qualitative as well as quantitative investigation of the drug-polymer interaction by Fourier transform infrared (FTIR) spectroscopy with a curve fitting program was undertaken. The release mechanisms of theophylline in pH 1.2 and pH 6.8 media were also studied to elucidate the effect of drug-polymer interaction on the release characteristics of microcapsules. Direct evidence for a hydrogen bonding interaction between theophylline and Eudragit L in microcapsules was obtained. Moreover, the fraction of hydrogen bonded theophylline increased with the increase of Eudragit L. The dissolution of theophylline from microcapsules exhibited an enteric-coated release property. The drug release mechanism was found to fit the Higuchi matrix model in the simulated gastric acid condition, but drug release was much more rapid in the pH 6.8 buffer solution. The drug release rate decreased as the composition of theophylline increased, and it was proportional to the fraction of hydrogen bonded theophylline. These results suggest that the increased fraction of hydrogen bonded theophylline in microencapsulation might improve the mixing and dispersibility of theophylline in the Eudragit L matrix, thus resulting in the increase of the release rate of theophylline from microcapsules.

  13. CYP1A2 polymorphism and theophylline clearance in Korean non-smoking asthmatics

    National Research Council Canada - National Science Library

    Yim, Eun-Young; Kang, Hye-Ryun; Jung, Jae-Woo; Sohn, Seong-Wook; Cho, Sang-Heon

    2013-01-01

    .... However, the underlying mechanism remains unknown in humans. We investigated the relationship between differences in theophylline clearance and genetic polymorphisms in the CYP1A2 and CYP2E1 gene in 89 Korean asthmatic patients...

  14. Comparison of the effects of two drying methods on polymorphism of theophylline

    DEFF Research Database (Denmark)

    Airaksinen, Sari; Karjalainen, Milja; Räsänen, Eetu

    2004-01-01

    Processing-induced transformations in drug formulation may induce adverse biopharmaceutical changes in the finished product. During the drying phase of wet granulation, theophylline monohydrate transforms either the stable (form I), or a polymorphic, metastable (form I(*)) form of anhydrous...... theophylline. We investigated the effect of two drying methods (multichamber microscale fluid bed dryer MMFD) or variable temperature X-ray powder diffractometer (VT-XRPD) on the relative amounts of the different theophylline forms remaining in the dried granules. Granules were analyzed using XRPD and near......-infrared spectroscopy. Form I(*) was the predominant form of theophylline after drying at 40-50 degrees C with both drying techniques. Although drying at temperatures over 50 degrees C produced mostly form I, more than 20% of form I(*) remained even at 90 degrees C when drying in MMFD. In these conditions, humidity had...

  15. Theophylline is able to partially revert cachexia in tumour-bearing rats

    Directory of Open Access Journals (Sweden)

    Olivan Mireia

    2012-08-01

    Full Text Available Abstract Background and aims The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves on a rat model of cancer cachexia. Methods The in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. Results Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart, which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. Conclusion Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.

  16. Theophylline Cocrystals Prepared by Spray Drying: Physicochemical Properties and Aerosolization Performance

    National Research Council Canada - National Science Library

    Alhalaweh, Amjad; Kaialy, Waseem; Buckton, Graham; Gill, Hardyal; Nokhodchi, Ali; Velaga, Sitaram P

    2013-01-01

    The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler...

  17. Invivo absorption behaviour of theophylline from starch-methyl methacrylate matrix tablets in beagle dogs.

    Science.gov (United States)

    Fernández-Campos, F; Ferrero, C; Colom, H; Jiménez-Castellanos, M R

    2015-01-30

    This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices(*) using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters. The principle of superposition was applied to predict multiple dose plasma concentrations from experimental single dose data. An in vitro-in vivo correlation (IVIVC) was also assessed. The sustained absorption kinetics of theophylline from these formulations was demonstrated by comparison with two commercially available oral sustained-release theophylline products (Theo-Dur(®) and Theolair(®)). A one-compartment model with first order kinetics without lag-time best describes the absorption/disposition of theophylline from the formulations. Results revealed a theophylline absorption rate in the order FD-HSMMA≥Theo-Dur(®)≥OD-CSMMA>Theolair(®)≥FD-CSMMA. On the basis of simulated plasma theophylline levels, a twice daily dosage (every 12h) with the FD-CSMMA tablets should be recommended. A Level C IVIVC was found between the in vitrot50% and the in vivo AUC/D, although further optimization of the in vitro dissolution test would be needed to adequately correlate with in vivo data. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. [Effect of EUDRAGIT® RS on the release behaviour of theophylline solid dispersions].

    Science.gov (United States)

    Orugun, Oluwaseun; Oyi, Avosuahi; Olowosulu, Adeniji; Apeji, Yonni; Olayemi, Olubunmi

    The purpose of this study was to extend the release of theophylline using Eudragit® RS 100 and Eudragit® RSPO as carriers. Solid dispersions of theophylline were prepared by the solvent evaporation technique using Eudragit® RS 100, Eudragit® RSPO and their blend in various drug : polymer ratios. The prepared solid dispersions were characterized with respect to entrapment efficiency, solubility and recovery yield. In vitro drug release of theophylline from the solid dispersions was evaluated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. Solubility studies demonstrated a decrease in the solubility of the drug from the solid dispersions. The solubilities of pure drug and solid dispersions were lowered in SGF compared to SIF. Solid dispersions prepared with Eudragit® RS 100 entrapped a greater amount of theophylline in comparison to those with Eudragit® RSPO or the polymer blends and were able to extend the release of theophylline over 24 hrs. Formulation SD4 released 95.52% of the drug in SIF and 93.56% in SGF. Hence, it was selected as the optimized formulation because it was able to extend the release of theophylline over 24 hrs.Key words: solid dispersion extended release Eudragit® drug release.

  19. The airway effects of stopping regular oral theophylline in patients with asthma

    Science.gov (United States)

    Bennett, J A; Thompson Coon, J; Pavord, I D; Wilding, P J; Tattersfield, A E

    1998-01-01

    Aims We investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. Methods Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg−1 day−1 or placebo for 2 weeks in a double-blind crossover study. FEV1 and PD20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose. PD20 AMP was measured before treatment and 9 h after the final dose. Results Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD20 histamine or FEV1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV1 (mean difference 0.15 l, 95% CI 0.03, 026) and PD20 AMP compared to placebo but no difference in other end points. Conclusions The small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance. PMID:9578190

  20. A meta-analysis on the efficacy of oral theophylline in patients with stable COPD

    Science.gov (United States)

    Molfino, Néstor A; Zhang, Peter

    2006-01-01

    Background Theophylline is a nonspecific inhibitor of phosphodiesterases that, despite exerting bronchodilator and anti-inflammatory effects, is a third-line therapy rarely used to treat chronic airflow limitation. We wished to evaluate the efficacy of oral theophylline as measured by improvements in trough (pre-dose) or peak (post-dose) FEV1 and FVC in patients with clinically stable COPD. Design Meta-analysis of randomized, placebo-controlled trials reported as of June 2005 in which theophylline was orally administered to stable COPD patients and the functional evaluations included pre- and post-theophylline values for FEV1 and FVC. Results A total of 18 trials were included in the meta-analysis. The weighted mean differences (WMD) with 95% confidence intervals (95% CI) for improvement over placebo in trough FEV1 and FVC were 0.108L (0.053–0.163) and 0.186L (0.036–0.336), respectively, while peak FEV1 and FVC improved by 0.096L (0.044–0.147) and 0.242L (0.11–0.374), respectively. Conclusions Treatment with oral theophylline improves both trough and peak FEV1 and FVC in clinically stable COPD patients. These results support previously reported benefits of theophylline in COPD. PMID:18046863

  1. Effect of Moisture on Powder Flow Properties of Theophylline

    Directory of Open Access Journals (Sweden)

    Niklas Sandler

    2010-07-01

    Full Text Available Powder flow is influenced by environmental factors, such as moisture and static electricity, as well as powder related factors, such as morphology, size, size distribution, density, and surface area. Pharmaceutical solids may be exposed to water during storage in an atmosphere containing water vapor, or in a dosage form consisting of materials (e.g., excipients that contain water and are capable of transferring in to other ingredients. The effect of moisture on powder flowability depends on the amount of water and its distribution. The aim of this work was to examine the effect of humidity on the flow properties of theophylline using information derived from solid-state analysis of the systems investigated.

  2. Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats.

    Science.gov (United States)

    Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal; Mittal, Monika; Porwal, Konica; Shrivastava, Richa; Taneja, Isha; Hossain, Zakir; Mandalapu, Dhanaraju; Gayen, Jiaur R; Wahajuddin, Muhammad; Sharma, Vishnu Lal; Trivedi, Arun K; Sanyal, Sabyasachi; Bhadauria, Smrati; Godbole, Madan M; Gupta, Sushil K; Chattopadhyay, Naibedya

    2016-03-15

    The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH)2 vitamin D3 (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Predictive Factors for Efficacy and Safety of Prophylactic Theophylline for Extubation in Infants with Apnea of Prematurity.

    Science.gov (United States)

    Kondo, Tomoko; Kondo, Yuki; Orita, Yuji; Mitarai, Fumi; Ishitsuka, Yoichi; Irikura, Mitsuru; Shimodozono, Yoshihiro; Douchi, Tsutomu; Takeda, Yasuo; Irie, Tetsumi

    2016-01-01

    This study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP) after weaning from mechanical ventilation. We retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine) for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013. A total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0%) infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p theophylline (specificity, 66.7%; sensitivity, 86.6%; p Adverse reactions were identified in 21 (21.0%) infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01). Physicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth.

  4. Predictive Factors for Efficacy and Safety of Prophylactic Theophylline for Extubation in Infants with Apnea of Prematurity.

    Directory of Open Access Journals (Sweden)

    Tomoko Kondo

    Full Text Available This study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP after weaning from mechanical ventilation.We retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013.A total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0% infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p < 0.001. Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline (specificity, 66.7%; sensitivity, 86.6%; p < 0.001; area under the curve, 0.750; 95% confidence interval, 0.45-0.74. Adverse reactions were identified in 21 (21.0% infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01.Physicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth.

  5. Efficacy of theophylline in people with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Ram, F S F; Jardin, J R; Atallah, A; Castro, A A; Mazzini, R; Goldstein, R; Lacasse, Y; Cendon, S

    2005-02-01

    To determine the efficacy of oral theophylline compared with placebo in people with stable chronic obstructive pulmonary disease (COPD). Systematic review of randomized-controlled trials comparing oral theophylline with placebo for a minimum of 7 days in people with stable COPD. Twenty randomized-controlled trials were included in this review. The following outcomes showed significant improvement with theophylline compared with placebo: FEV1 and FVC both improved with theophylline (weighted mean difference [WMD] 0.10 L; 95% confidence interval [95% CI] 0.04-0.16 and WMD 0.21 L; 95% CI 0.10-0.32, respectively). VO2 max also improved with theophylline (WMD 195.27mL/ min; 95% CI 112.71-277.83), as did PaO2 and PaCO2 (WMD 3.18 mmHg; 95% CI 1.23-5.13 and WMD -2.36mmHg; 95% CI -3.52 to -1.21, respectively). Patients preferred theophylline over placebo (relative risk 2.27; 95% CI 1.26-4.11). Theophylline increased the risk of nausea compared with placebo (RR 7.67; 95% CI 1.47-39.94). This review has shown that theophylline still has a role in the management of stable COPD, and is preferred by patients over placebo. However, the benefits of theophylline in stable COPD have to be weighed against the risk of adverse effects.

  6. Two Distinct Pathways for Metabolism of Theophylline and Caffeine Are Coexpressed in Pseudomonas putida CBB5▿ †

    Science.gov (United States)

    Yu, Chi Li; Louie, Tai Man; Summers, Ryan; Kale, Yogesh; Gopishetty, Sridhar; Subramanian, Mani

    2009-01-01

    Pseudomonas putida CBB5 was isolated from soil by enrichment on caffeine. This strain used not only caffeine, theobromine, paraxanthine, and 7-methylxanthine as sole carbon and nitrogen sources but also theophylline and 3-methylxanthine. Analyses of metabolites in spent media and resting cell suspensions confirmed that CBB5 initially N demethylated theophylline via a hitherto unreported pathway to 1- and 3-methylxanthines. NAD(P)H-dependent conversion of theophylline to 1- and 3-methylxanthines was also detected in the crude cell extracts of theophylline-grown CBB5. 1-Methylxanthine and 3-methylxanthine were subsequently N demethylated to xanthine. CBB5 also oxidized theophylline and 1- and 3-methylxanthines to 1,3-dimethyluric acid and 1- and 3-methyluric acids, respectively. However, these methyluric acids were not metabolized further. A broad-substrate-range xanthine-oxidizing enzyme was responsible for the formation of these methyluric acids. In contrast, CBB5 metabolized caffeine to theobromine (major metabolite) and paraxanthine (minor metabolite). These dimethylxanthines were further N demethylated to xanthine via 7-methylxanthine. Theobromine-, paraxanthine-, and 7-methylxanthine-grown cells also metabolized all of the methylxanthines mentioned above via the same pathway. Thus, the theophylline and caffeine N-demethylation pathways converged at xanthine via different methylxanthine intermediates. Xanthine was eventually oxidized to uric acid. Enzymes involved in theophylline and caffeine degradation were coexpressed when CBB5 was grown on theophylline or on caffeine or its metabolites. However, 3-methylxanthine-grown CBB5 cells did not metabolize caffeine, whereas theophylline was metabolized at much reduced levels to only methyluric acids. To our knowledge, this is the first report of theophylline N demethylation and coexpression of distinct pathways for caffeine and theophylline degradation in bacteria. PMID:19447909

  7. Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives.

    Science.gov (United States)

    Ruddarraju, Radhakrishnam Raju; Murugulla, Adharvana Chari; Kotla, Ravindar; Chandra Babu Tirumalasetty, Muni; Wudayagiri, Rajendra; Donthabakthuni, Shobha; Maroju, Ravichandar; Baburao, K; Parasa, Lakshmana Swamy

    2016-11-10

    A new series of theophylline containing acetylene derivatives (6a-6b and 7-13) and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives (20-32) have been designed and synthesized. These compounds were screened for anticancer and antimicrobial activity. Further the computational docking and 2D QSAR were performed using MOE software to identify novel scaffolds. The results showed that compound 29 and 30 exhibit significant cytotoxic effect on all four cancer cells such as lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375) with IC50 values of 2.56, 2.19, 1.89, 4.89 μM and 3.57, 2.90, 2.10, 5.81 μM respectively. Whereas quite different results were observed for these compounds in antimicrobial studies. Compounds 11, 21 and 26 have exhibited significant minimum inhibitory concentrations (MIC) against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The docking studies demonstrate that compound 27, 28, 29 and 30 have good dock score and binding affinities with various therapeutic targets in cancer cell proliferation. In addition these compounds have shown acceptable correlation with bioassay results in the regression plots generated in 2D QSAR models. This is the first report to demonstrate the theophylline containing acetylene derivatives and theophylline containing 1,2,3-triazole nucleoside hybrids as potential anticancer and antimicrobial agents with comprehensive in silico analysis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Effect of theophylline on sleep-disordered breathing in heart failure.

    Science.gov (United States)

    Javaheri, S; Parker, T J; Wexler, L; Liming, J D; Lindower, P; Roselle, G A

    1996-08-22

    Theophylline has been used to treat central apnea associated with Cheyne-Stokes respiration (periodic breathing). We studied the effect of short-term oral theophylline therapy on periodic breathing associated with stable heart failure due to systolic dysfunction. Fifteen men with compensated heart failure (left ventricular ejection fraction, 45 percent or less) participated in the study. Their base-line polysomnograms showed periodic breathing, with more than 10 episodes of apnea and hypopnea per hour. In a double-blind crossover study, the patients received theophylline or placebo orally twice daily for five days, with one week of washout between the two periods. After five days of treatment, the mean (+/-SD) plasma theophylline concentration was 11 +/- 2 microgram per milliliter. Theophylline therapy resulted in significant decreases in the number of episodes of apnea and hypopnea per hour (18 +/- 17, vs. 37 +/- 23 with placebo and 47 +/- 21 at base line; Parterial oxyhemoglobin saturation was less than 90 percent (6 +/- 11 percent, vs., 23 +/- 37 and 14 +/- 14 percent, respectively; Parterial oxyhemoglobin desaturation during sleep.

  9. The effect of coenzyme Q10 on the pharmacokinetic parameters of theophylline.

    Science.gov (United States)

    Baskaran, Rengarajan; Shanmugam, Srinivasan; Nagayya-Sriraman, Santhoshkumar; Kim, Ju Hyun; Jeong, Tae Chun; Yong, Chul Soon; Choi, Han-Gon; Yoo, Bong Kyu

    2008-07-01

    Interaction of a drug with other drugs and dietary supplements is becoming an emerging issue for patients and health insurance authorities due to awareness of adverse drug event. In this study, we examined the effects of coenzyme Q10 (CoQ10), one of the most popular dietary supplements, on the pharmacokinetic parameters of theophylline in rats. The pharmacokinetic parameters of theophylline changed significantly when the drug was administered after five consecutive days of pretreatment with CoQ10. Time to reach maximum plasma concentration of theophylline delayed when the drug was administered after the pretreatment with CoQ10. Maximum plasma concentration and area under the curve of theophylline were about two-fold increased and other pharmacokinetic parameters such as half-life and volume of distribution were also changed significantly. Therefore, although CoQ10 is generally considered a safe dietary supplement, it appears that patients on theophylline therapy should use caution when they take CoQ10.

  10. Theophylline versus acetaminophen in the treatment of post-dural puncture headache (PDPH).

    Science.gov (United States)

    Mahoori, Alireza; Hassani, Ebrahim; Noroozinia, Heydar; Javaheri, Negin; Hatami, Sanaz

    2013-10-01

    Post-dural puncture headache (PDPH) is the most frequent complication of procedures associated with dural puncture for spinal anesthesia or following accidental dural puncture during epidural anesthesia. Since invasive treatments have known complications, pharmacologic management may be preferable. The aim of this study was to evaluate and compare the efficacy of theophylline and Acetaminophen in treatment of PDPH. In this single-blind randomized clinical trial, 60 patients with Class I physical status according to ASA classification system, who suffered from PDPH were enrolled. Patients in Theophylline group were received theophylline tablet 250 mg three times per day, and in the other group acetaminophen 500 mg three times per day was administered. Pain intensity was assessed 2, 6, and 12 hour after drug administration using 0-10 cm Visual Analog Scale. The main VAS values is significantly lower in theophylline group in comparison with the acetaminophen group at 2 (5 +/- 1.57 vs. 5.97 +/- 1.27), 6 (3.43 +/- 1.73 vs. 4.33 +/- 1.49), and 12 (2.67 +/- 2.35 vs. 4.24 +/- 1.97) hours after drug administration (p adverse effects were reported. Theophylline is a safe and effective treatment for PDPH. It may be tried in PDPH patients before using any invasive technique. Further investigations studying other Methylxanthines are recommended as well.

  11. The novel combination of theophylline and bambuterol as a potential treatment of hypoxemia in humans.

    Science.gov (United States)

    Strand, Trond-Eirik; Khiabani, Hasse Z; Boico, Alina; Radiloff, Daniel; Zhao, Yulin; Hamilton, Karyn L; Christians, Uwe; Klawitter, Jelena; Noveck, Robert J; Piantadosi, Claude A; Bell, Christopher; Irwin, David; Schroeder, Thies

    2017-09-01

    Hypoxemia can be life-threatening, both acutely and chronically. Because hypoxemia causes vascular dysregulation that further restricts oxygen availability to tissue, it can be pharmacologically addressed. We hypothesized that theophylline can be safely combined with the β2-adrenergic vasodilator bambuterol to improve oxygen availability in hypoxemic patients. Ergogenicity and hemodynamic effects of bambuterol and theophylline were measured in rats under hypobaric and normobaric hypoxia (12% O2). Feasibility in humans was assessed using randomized, double-blind testing of the influence of combined slow-release theophylline (300 mg) and bambuterol (20 mg) on adverse events (AEs), plasma K+, pulse, blood pressure, and drug interaction. Both drugs and their combination significantly improved hypoxic endurance in rats. In humans, common AEs were low K+ (theophylline: 4, combination: 13 episodes) and tremors (10, 0, 14 episodes). No exacerbation or serious AE occurred when drugs were combined. A drop in plasma K+ coincided with peak bambuterol plasma concentrations. Bambuterol increased heart rate by approximately 13 bpm. Drug interaction was present but small. We report promise, feasibility, and relative safety of combined theophylline and bambuterol as a treatment of hypoxemia in humans. Cardiac safety and blood K+ will be important safety endpoints when testing these drugs in hypoxemic subjects.

  12. Effects of Theophylline on Pulmonary Function in Patients With Traumatic Tetraplegia

    Science.gov (United States)

    Tzelepis, George E; Bascom, Amy T; Badr, M Safwan; Goshgarian, Harry G

    2006-01-01

    Background/Objective: To assess the effects of theophylline on pulmonary function in patients with chronic traumatic tetraplegia, we conducted a double-blind placebo-controlled crossover study in 10 patients. Methods: The patients (age: 41 ± 3 years; time from injury: 16 ± 3 years; neurological levels: C3 to C7-T1) were randomized to receive oral theophylline or placebo for 6 weeks. After 2 months of washout, the patients received the medication not taken in the first trial for an additional 6 weeks. We measured lung volumes, expiratory flow rates, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) at both baseline and at the end of each treatment arm. Theophylline blood serum assays were measured during the first week of the treatment and on the day of respiratory measurements. Results: Mean theophylline level on the day of treatment completion was 12.6 ± 1.4 μg/mL. In analyzing the data from the group of 10 patients, the percent changes from baseline in total lung capacity, forced vital capacity, forced expiratory volume at 1 second, MIP, and MEP did not differ significantly between the two treatment arms (P > 0.05 in all). Conclusions: These data show that in this small group of 10 subjects with chronic tetraplegia, administration of oral theophylline did not improve pulmonary function. PMID:16859226

  13. A highly sensitive gold nanoparticle-based electrochemical aptasensor for theophylline detection.

    Science.gov (United States)

    Chen, Xifeng; Guo, Zhenzhen; Tang, Yuguo; Shen, Ying; Miao, Peng

    2018-01-25

    Theophylline is a common bronchodilator for the treatment of diseases like asthma, bronchitis and emphysema. However, it should be strictly used and monitored due to its toxicity when the concentration is above certain levels. In this work, an electrochemical biosensor for theophylline detection is proposed by recognition of RNA aptamer and gold nanoparticle (AuNP)-based amplification technique. First, RNA aptamer is splitted into two single-stranded RNA probes. One is hybridized with DNA tetrahedron and the resulted nanostructure is then immobilized onto a gold electrode; the other is modified on the surface of AuNPs which is also labeled with methylene blue (MB) as electrochemical species. The recognition process between the two RNA probes and theophylline causes the localization of AuNPs and the enrichment of MB on the electrode interface. A significant electrochemical response is thus generated which is related to the concentration of initial theophylline. This proposed aptasensor shows excellent sensitivity and selectivity which could also be applied in quantitatively detection of theophylline in serums samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The role of theophylline in prevention of radiocontrast media-induced nephropathy

    Directory of Open Access Journals (Sweden)

    Malhis Mahmoud

    2010-01-01

    Full Text Available Contrast media induced nephropathy (CIN results in significant morbidity and mortality. We therefore investigated whether theophylline (adenosine antagonist reduces the inci-dence of contrast media induced nephropathy. Two hundred and eighty patients were randomly assigned to prophylactic administration of hydration with sodium bicarbonate plus theophylline (either orally or intravenously (n=128 or hydration with sodium bicarbonate only (n=152. Blood Urea, creatinine, and glomerular filtration rate (MDRD were measured before and after administration of contrast media. Both groups were similar in clinical characteristics and amount of contrast used. Theophylline prophylaxis significantly reduced the incidence of CIN (1.6% vs 7.9%; P= 0.015. Compared to low-risk patients, Theophylline prophylaxis significantly reduced the incidence of CIN in moderate and high-risk patients (0% vs 8.8%; P= 0.022 and 9.1% vs 42.1%; P= 0.014 respectively. In conclusion, prophylactic administration of theophylline re-duces the incidence of CIN in moderate and high-risk patients for CIN.

  15. The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in patients with cancer.

    Science.gov (United States)

    Karademir, Lutfiye Derya; Dogruel, Fatma; Kocyigit, Ismail; Yazici, Cevat; Unal, Aydin; Sipahioglu, Murat Hayri; Oymak, Oktay; Tokgoz, Bulent

    2016-06-01

    Cisplatin is a potent antineoplastic agent used and its major limiting side effect is nephrotoxicity. The aims of the study are early detection of acute kidney injury (AKI) with biomarkers and investigation of the potential nephron-protective effects of theophylline. Glomerular filtration rates (GFR), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C were measured at 5th day of treatment in all of the patients. In addition, these parameters were measured repeatedly after the administration of cisplatin, at 2nd hour, 5th and 20th days. Sixty patients who are planned to receive cisplatin for the first time were included in the study. Patients were divided into two groups as Group 1 (n = 30) (standard treatment arm) and Group II (n = 30) (theophylline arm). In both groups after the administration of cisplatin, GFR showed a significant decrease within time (p = 0.006). Urine NGAL levels were significantly high after 2 h of cisplatin administration (p theophylline (p = 0.025). After 5 days of cisplatin administration, urine protein levels were significantly higher in both groups (p Theophylline was found not to bring a complete protection for the kidneys, but less nephrotoxicity was developed when compared to the group not receiving theophylline.

  16. A theophylline quartz crystal microbalance biosensor based on recognition of RNA aptamer and amplification of signal.

    Science.gov (United States)

    Dong, Zong-Mu; Zhao, Guang-Chao

    2013-04-21

    A quartz crystal microbalance (QCM) biosensor for theophylline was developed by recognition of RNA aptamer and gold nanoparticle amplification technique. Firstly, a designed small single-stranded RNA, RNA1, was immobilized onto the QCM electrode through a thiol linker. Then, the complementary stranded RNA2, which can combine with RNA1 to form a double-stranded RNA with a recognition unit of theophylline, could be self-assembled on the QCM electrode surface through a hybrid reaction in the presence of theophylline. The recognition process could cause a frequency change of QCM to give the signal related to theophylline. When RNA2 was tethered to gold nanoparticles, the signal could be amplified to further enhance the sensitivity of the designed sensor. Under the optimal conditions, the QCM-based biosensor showed excellent sensitivity (limit of detection, 8.2 nM) and specificity with a dissociation constant of Kd = 5.26 × 10(-7) M. The sensor can be used to quantitatively detect theophylline in serum, suggesting that it can be applied in complex biological samples.

  17. A method for the determination of theophylline in serum by isotope dilution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Susanto, F.; Humfeld, S.; Niederau, C.M.; Reinauer, H. (Dept. of Clinical Biochemistry, Duesseldorf Univ. (Germany))

    1992-12-01

    A method for the determination of theophylline in human serum by the isotope dilution/mass spectrometric technique is described. As an internal standard labelled (1,3-[sup 15]N[sub 2]-2-[sup 13]C)theophylline is added to the serum sample. The analyte and internal standard are extracted with chloroform/2-propanol (90:10) and converted to the trimethylsilyl derivatives. The extraction and silylation procedures are checked by adding theophylline and internal standard in various concentrations to blank serum and determining the recovery. The trimethylsilyl derivatives of labelled and non-labelled theophylline are separated and detected by GC-MS with the mass spectrometer set to m/z 252 and 255. The amounts of theophylline in the serum are calculated from the isotope ratios measured by selected ion monitoring. The accuracy, precision and recovery of this GC-MS method are presented and discussed. The coefficient of variation determined from duplicate samples was less than 2.5%. The detection limit was 10 ng/ml at a signal-to-noise ratio of 3:1. (orig.).

  18. Pharmacokinetic interaction of Acacia catechu with CYP1A substrate theophylline in rabbits.

    Science.gov (United States)

    Al-Mohizea, Abdullah Mohammed; Raish, Mohammad; Ahad, Abdul; Al-Jenoobi, Fahad Ibrahim; Alam, Mohd Aftab

    2015-10-01

    To investigate the effect of black catechu (BC) on the pharmacokinetics of theophylline (CYP1A2 substrate, with narrow therapeutic index) in rabbits. In the present investigation the effect of BC on the pharmacokinetics of theophylline, a CYP1A2 substrate was determined. In the study, BC (264 mg/kg, p. o.) or saline (control group) was given to rabbits for 7 consecutive days and on the 8th day theophylline (16 mg/kg) was administered orally one hour after BC or saline treatment. Blood samples were withdrawn at different time intervals (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h) from the marginal ear vein. The pretreatment of rabbits with BC resulted in a significant increase in maximum blood concentration, time of peak concentration and area under the concentration time profile curve until last observation which was about 41.32%, 35.71% and 15.03%, respectively. While decreases in clearance, volume of distribution, and half-life were observed. It is suggested that BC pretreatment decreases the CYP1A metabolic activity leading to increase in bioavailability and decrease in oral clearance of theophylline, which may be due to inhibition of CYP1A. BC can significantly alter theophylline pharmacokinetics in vivo possibly due to inhibition of CYP1A and P-glycoprotein activity. Based on these results, precaution should be exercised when administering BC with CYP1A substrate.

  19. Protective effect of theophylline on renal functions in experimental pneumoperitoneum model.

    Science.gov (United States)

    Ozturk, Sefa Alperen; Ceylan, Cavit; Serel, Tekin Ahmet; Doluoglu, Omer Gokhan; Soyupek, Arap Sedat; Guzel, Ahmet; Özorak, Alper; Uz, Efkan; Savas, Hasan Basri; Baspinar, Sirin

    2015-07-01

    Our objective in this experimental study is to research the effect of the intra-abdominal pressure which rises following pneumoperitoneum and whether Theophylline has a possible protective activity on this situation. In our study, 24 Wistar Albino rats were used. Rats were divided into two groups. The first group was set for only pneumoperitoneum model. The second group was given 15 mg/kg of Theophylline intraperitoneally before setting pneumoperitoneum model. Then urea, creatinine, cystatin-C, tissue and serum total antioxidant capacity, total oxidant capacity and oxidative stress index in two groups were measured and compared with each other. Apoptosis and histopathological conditions in the renal tissues were examined. The differences between the groups were analyzed with the Mann-Whitney U test. Results were considered significant at p 0.05). The mean value of urea were similar in pneumoperitoneum and pneumoperitoneum + theophylline groups (p = 0.12). The mean cystatin-C value was 2.2 ± 0.3 µg/mL in pneumoperitoneum, 1.74 ± 0.33 µg/mL in pneumoperitoneum + theophylline (p = 0.002). According to our study, lower cystatin-C levels in the group, where Theophylline was given, are suggestive of lower renal injury in this group. However, this opinion is interrogated as there is no difference in terms of tissue and serum TAS, TOS, OSI and urea values between the groups.

  20. The effect of theophylline on the prevention of mechanical ventilation-induced diaphragm atrophy in rats.

    Science.gov (United States)

    Aydin, Nihal Bakirkalay; Teke, Turgut; Toy, Hatice; Uzun, Kursat

    2014-01-01

    Movement disorders and atrophy occur in the diaphragm, the most important muscle of respiration, because of mechanical ventilation (MV). In this animal model, we aimed to evaluate the effect of intravenous theophylline administration on the prevention of mechanical ventilation-induced diaphragmatic atrophy. In our study, 30 healthy male Sprague-dawley rats were used. They were divided into 3 equal groups. Group 1: the control group (no MV); group 2: the placebo group that received MV; Group 3: the theophylline group composed of rats that received both MV and theophylline therapy. In all 3 groups, the diaphragmatic atrophy was evaluated histopathologically. In the histopathological examination, no macroscopic thickening and microscopic atrophy were observed in the diaphragm in the control group. In the placebo group (group 2), macroscopically definite thickening was observed in all rats, and microscopically, heavy (+++) atrophy was observed. In the theophylline group (group 3), there was no atrophy in one rat. In 8 rats, light (+), and in 1 rat medium (++) atrophy was observed. In our study, it was shown that atrophy occurred in the diaphragms of rats after MV, and the atrophy was decreased after theophylline administration.

  1. The effects of mono- and divalent metal cations on the solution structure of caffeine and theophylline

    Science.gov (United States)

    Nafisi, Shohreh; Monajemi, Majid; Ebrahimi, Saeedeh

    2004-11-01

    The interactions of caffeine and theophylline with potassium +, cobalt 2+ and nickel 2+ ions were studied in aqueous solution at physiological pH with constant ligand concentration and various metal ion contents. Fourier Transform infrared spectroscopy and absorption spectra were used to determine the cation binding mode and association constants. Spectroscopic results showed direct and indirect cation interactions for Co 2+, Ni 2+ and K + through O6 and N9 atoms (caffeine) and O6, N9 and N7 atoms (theophylline). The overall binding constants were, K(Co-caffeine)=6.92×10 4 M -1, K(Ni-caffeine)=2.22×10 4 M -1, K(K-caffeine)=5.08×10 3 M -1, K(Co-theophylline)=5.06×10 4 M -1, K(Ni-theophylline)=4.84×10 4 M -1 and K(K-theophylline)=2.13×10 3 M -1. The association constants showed weaker interaction for monovalent cation than divalent metal ions.

  2. Renal actions of theophylline and atrial natriuretic peptide in humans: a comparison by means of clearance studies

    NARCIS (Netherlands)

    Beutler, J. J.; Koomans, H. A.; Bijlsma, J. A.; Dorhout Mees, E. J.

    1990-01-01

    The hypothesis that the methylxanthine theophylline and atrial natriuretic peptide (ANP) have similar actions in the kidney was tested. Doses of equal natriuretic potency were administered to seven healthy men during maximal water diuresis. Theophylline (1.2 mg/kg/min) increased sodium excretion to

  3. Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats.

    Science.gov (United States)

    Ueng, Yune-Fang; Tsai, Tung-Hu; Don, Ming-Jaw; Chen, Ruei-Ming; Chen, Ta-Liang

    2005-02-01

    Rutaecarpine is a main active alkaloid present in the medicinal herb, Evodia rutaecarpa. The cytochrome P450 (CYP) 1A2 substrate, theophylline, is an important therapeutic agent for the treatment of asthma, but has a narrow therapeutic index. To evaluate the pharmacokinetic interaction of theophylline with rutaecarpine, the effects of rutaecarpine on CYP1A2 activity and theophylline pharmacokinetics were investigated. Oral treatment of Sprague-Dawley rats with 50 mg kg(-1) rutaecarpine for three days through a gastrogavage caused a 4- and 3-fold increase in liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activity, respectively. In the kidney, rutaecarpine treatment caused a 3-fold increase in EROD activity. In the lungs, EROD activity was elevated from an undetectable to a detectable level by rutaecarpine. Pharmacokinetic parameters of theophylline were determined using a microdialysis sampling method. Rutaecarpine pre-treatment increased the clearance of theophylline in a dose-dependent manner. Pre-treatment of rats with 50 mg kg(-1) rutaecarpine caused a 3-fold increase in theophylline clearance and a 70%, 68% and 68% decrease in the area under the concentration-time curve (AUC), mean residence time (MRT) and half-life, respectively. These results demonstrated that rutaecarpine treatment elevated CYP1A2 catalytic activity and theophylline excretion in rats. In patients taking theophylline, adverse effects might be noticed when a rutaecarpine-containing herbal preparation is used concomitantly.

  4. Concurrent administration of donepezil HCl and theophylline: assessment of pharmacokinetic changes following multiple-dose administration in healthy volunteers

    Science.gov (United States)

    Tiseo, P J; Foley, K; Friedhoff, L T

    1998-01-01

    Aim The aim of the study was to evaluate the pharmacokinetics of theophylline administered alone, and in combination with donepezil HCl, following multiple-dose administration of both drugs in healthy volunteers. Methods This was an open-label, randomized, two-period crossover study in healthy male volunteers (n = 12). During each treatment period, subjects received either titrated-dose theophylline alone, or in combination with donepezil (5 mg, once daily) for 10 consecutive days. On day 10 of each treatment period, serial blood samples for the determination of theophylline concentrations in plasma were measured up to 24 h. Treatment periods were separated by a 3-week, drug-free washout. Plasma concentrations of theophylline were determined by HPLC with UV detection. Results No statistically significant differences in theophylline pharmacokinetics (Cmax, AUC or tmax) were observed between theophylline administered alone and in combination with donepezil. No clinically significant changes in vital signs, ECG parameters or clinical laboratory tests were observed in any subject during any treatment period. Conclusions Concurrent administration of donepezil HCl does not alter the pharmacokinetic profile of theophylline following multiple-dose administration of both drugs in healthy volunteers. These findings suggest that donepezil may be safely co-administered with theophylline without a need for dose modification or additional monitoring procedures. PMID:9839764

  5. Potent bronchodilating effects of enprofylline and theophylline on contractions induced by egg albumin or by slow reacting substance (SRS).

    Science.gov (United States)

    Hedman, S E; Andersson, R G

    1984-08-01

    Isolated sensitized guinea pig tracheal smooth muscle tone was induced by use of egg albumin or SRS-A (slow reacting substance of anaphylaxis). The dose-response relationships of theophylline and enprofylline were studied on these preparations. Enprofylline was more potent than theophylline in relaxing the egg albumin- or SRS-A-induced tracheal muscle tone. The theophylline relaxation-curve was significantly shifted to the left after addition of adenosine-deaminase to the egg albumin-contracted trachea, but this was not observed with the enprofylline relaxation-curve. In SRS-A-contracted tracheas, the addition of adenosine-deaminase did not significantly alter the relaxation curves of theophylline or enprofylline. It is therefore suggested that the relaxing effects of theophylline and enprofylline on SRS-A-induced contractions, at the therapeutically relevant concentrations demonstrated in this study, might be of importance for the anti-asthmatic effects of xanthines.

  6. Theophylline action on primary human bronchial epithelial cells under proinflammatory stimuli and steroidal drugs: a therapeutic rationale approach.

    Science.gov (United States)

    Gallelli, Luca; Falcone, Daniela; Cannataro, Roberto; Perri, Mariarita; Serra, Raffaele; Pelaia, Girolamo; Maselli, Rosario; Savino, Rocco; Spaziano, Giuseppe; D'Agostino, Bruno

    2017-01-01

    Theophylline is a natural compound present in tea. Because of its property to relax smooth muscle it is used in pharmacology for the treatment of airway diseases (ie, chronic obstructive pulmonary disease, asthma). However, this effect on smooth muscle is dose dependent and it is related to the development of side effects. Recently, an increasing body of evidence suggests that theophylline, at low concentrations, also has anti-inflammatory effects related to the activation of histone deacetylases. In this study, we evaluated the effects of theophylline alone and in combination with corticosteroids on human bronchial epithelial cells under inflammatory stimuli. Theophylline administrated alone was not able to reduce growth-stimulating signaling via extracellular signal-regulated kinases activation and matrix metalloproteases release, whereas it strongly counteracts this biochemical behavior when administered in the presence of corticosteroids. These data provide scientific evidence for supporting the rationale for the pharmacological use of theophylline and corticosteroid combined drug.

  7. Influence of Air Temperature and Humidity on Dehydration Equilibria and Kinetics of Theophylline

    Directory of Open Access Journals (Sweden)

    Amira Touil

    2013-01-01

    Full Text Available The effect of hygrothermal conditions (air temperature and relative humidity on the dehydration of theophylline monohydrate was investigated. Firstly, the equilibrium states of theophylline were investigated. The data from gravimetric analysis at constant temperature and humidity were reported as desorption isotherms. The PXRD analysis was used to identify the different polymorphic forms of theophylline: the monohydrate, the metastable anhydrate, and the stable anhydrate. Solid-solid phase diagrams for two processing times were proposed. Secondly, the dehydration kinetics were studied. The water content evolutions with time were recorded at several temperatures from 20°C to 80°C and several relative humidities from 4% to 50%. Different mathematical models were used to fit the experimental data. The spatially averaged solution of 2D Fickian transient diffusion equation best represented the water mass loss versus time experimental relationship. The dehydration rate constant was found to increase exponentially with air temperature and to decrease exponentially with air relative humidity.

  8. Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats.

    Science.gov (United States)

    Carney, J. M.

    1982-01-01

    1 Rats were trained to respond under a variable interval 30 s (VI 30) schedule of food reinforcement. Caffeine (0.32-32 mg/kg), theophylline (1.0-56 mg/kg) and theobromine (10-320 mg/kg) in general produced dose-related decreases in operant responding. At relatively low doses, caffeine (1.0 mg/kg) and theophylline (3.2 mg/kg) produced slight but nonsignificant increases in VI 30 responding. 3 The rank order of potency for producing decreases in responding was caffeine greater than theophylline greater than theobromine. 4 Daily caffeine injections (32 mg/kg, i.p.) resulted in the development of caffeine tolerance. This tolerance was characterized by a 6 fold shift to the right in the caffeine dose-effect curve. Saline substitution for the 32.0 mg/kg caffeine maintenance dose resulted in a substantial decrease in responding. PMID:7066599

  9. A randomized controlled trial of theophylline versus CO2 inhalation for treating apnea of prematurity.

    Science.gov (United States)

    Al-Saif, Saif; Alvaro, Ruben; Manfreda, Juri; Kwiatkowski, Kim; Cates, Don; Qurashi, Mansour; Rigatto, Henrique

    2008-10-01

    To determine whether inhalation of 0.8% CO(2) in preterm infants decreases the duration and rate of apnea as effectively as or better than theophylline with fewer adverse side effects. A prospective, randomized, control study of 42 preterm infants of gestational age 27 to 32 weeks assigned to receive inhaled CO(2) (n = 21) or theophylline (n = 21). The study group had a mean (+/- standard error of the mean) birth weight of 1437 +/- 57 g, gestational age of 29.4 +/- 0.3 weeks, and postnatal age of 43 +/- 4 days. After a control period, 0.8% CO(2) or theophylline was given for 2 hours, followed by a recovery period. In the CO(2) group, apneic time and rate decreased significantly, from 9.4 +/- 1.6 seconds/minute and 94 +/- 15 apneic episodes/hour to 3.0 +/- 0.5 seconds/minute and 34 +/- 5 apneic episodes/hour. In the theophylline group, apneic time and rate decreased significantly, from 8 +/- 1 seconds/minute and 80 +/- 8 apneic episodes/hour to 2.5 +/- 0.4 seconds/minute and 28 +/- 3 apneic episodes/hour. Cerebral blood flow velocity (CBFV) decreased only during theophylline administration. Our findings suggest that inhaled low (0.8%) CO(2) concentrations in preterm infants is at least as effective as theophylline in decreasing the duration and number of apneic episodes, has fewer side effects, and causes no changes in CBFV. We speculate that CO(2) may be a better treatment for apnea of prematurity than methylxanthines.

  10. Synthesis and Study of Guest-Rebinding of MIP Based on MAA Prepared using Theophylline Template

    Science.gov (United States)

    Nurhayati, T.; Yanti; Royani, I.; Widayani; Khairurrijal

    2016-08-01

    A molecularly imprinted polymer (MIP) based on methacrylic acid (MAA) monomer and theophylline template has been synthesized using a modified bulk polymerization method. Theophylline was employed as a template and it formed a complex with MAA through hydrogen bonding. Self-assembly of template-monomer was followed by cross-linking process using ethylene glycol dimethacrylate (EGDMA) cross-linker. The polymerization process was initiated by thermal decomposition of benzoyl peroxide (BPO) as the initiator at 60oC after cooling treatment at -5oC. After 7 hours, a rigid polymer was obtained and followed by grinding the polymer and removing the template. As a reference, a nonimprinted polymer (NIP) has also been synthesized using similar procedure by excluding the template. FTIR study was carried out to investigate the presence of theophylline in the as- prepared polymer, MIP, and NIP. The spectra indicated that theophylline was successfully incorporated in the as-prepared polymer. This result was also confirmed by EDS analysis showing that N atoms of the as-prepared polymer were derived from amino group of theophylline. Furthermore, the polymer particles of MIP were irregular in shape and size as shown by its SEM image. The capability of guest-rebinding of the MIP was analyzed through Batchwise guest-binding experiment. The results showed that for initial concentration of theophylline in methanol/chloroform (1/1, v/v) of 0.333 mM, the binding capacity of the MIP was 23.22 /mol/g. Compared to the MIP, the adsorption capacity of the NIP was only 3.73 /mol/g. This result shows that MIP has higher affinity than NIP.

  11. Theophylline detection in serum using a self-assembling RNA aptamer-based gold nanoparticle sensor.

    Science.gov (United States)

    Jiang, Hongyan; Ling, Kai; Tao, Xiaojun; Zhang, Qiqing

    2015-08-15

    Recently, DNA aptamer-gold nanoparticle (AuNP) conjugates have emerged as novel biosensing tools. Although RNA aptamers are more advantageous than DNA aptamers, their vulnerable nature during the construction of these conjugates restricts the development of RNA aptasensors. In this study, we developed an RNA aptamer-based AuNP sensor for the detection of theophylline in serum, combining the high binding affinity and selectivity of a theophylline RNA aptamer and the fluorescence quenching ability of AuNPs. In order to prevent nuclease degradation during the experimental process, the single strand of the theophylline RNA aptamer (33-mer) was split at the end loop region into two shorter halves, which were able to reassemble to form the theophylline-binding pocket. One fragment was linked to a DNA sequence that included a 15 thymine (T15) spacer and a polyadenine (polyA, A12) tail. The chimeric RNA/DNA oligonucleotide was attached to AuNPs within a few minutes via adsorption of the polyA tail. The other fragment was labeled with a fluorophore (Cy3). The two individual fragments self-assembled in the presence of theophylline. Upon ligand binding, the fragments came into close proximity, resulting in fluorescence quenching. This sensor exhibited a low detection limit of 0.05 µM, with a linear dynamic range from 0.1 to 10 µM in serum. Moreover, the sensor did not recognize theophylline-related compounds (e.g., caffeine and theobromine), demonstrating its high selectivity. This strategy offers new possibilities for the application of RNA aptasensors in clinical settings. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Potentiation of the adverse effects of intravenous terbutaline by oral theophylline.

    Science.gov (United States)

    Smith, S R; Kendall, M J

    1986-01-01

    We have studied the influence of therapeutic plasma concentrations of theophylline on some of the unwanted responses to intravenous terbutaline in normal subjects. There was a significantly greater fall in serum potassium and rise in plasma glucose, pulse rate and systolic blood pressure in response to an intravenous infusion of terbutaline when theophylline was present compared with when terbutaline was given alone. These drugs are commonly used together in the treatment of acute asthma and potentiation of side effects may be hazardous. We suggest monitoring of the serum potassium when these drugs are used together during acute exacerbations of asthma. PMID:3707814

  13. Effects of excipients on hydrate formation in wet masses containing theophylline

    DEFF Research Database (Denmark)

    Airaksinen, Sari; Luukkonen, Pirjo; Jørgensen, Anna

    2003-01-01

    Transformations between solid phases in dosage forms can lead to instability in drug release. Thus, it is important to understand mechanisms and kinetics of phase transformations and factors that may influence them. During wet granulation theophylline shows pseudopolymorphic changes that may alter...... is able to take large amounts of water into its internal structure, it was able to inhibit the formation of theophylline monohydrate only at low moisture contents, not at the amounts of water needed to form granules. Both the spectroscopic methods used could identify the hydrate formation even though...

  14. Theophylline as an add-on to thrombolytic therapy in acute ischaemic stroke (TEA-Stroke)

    DEFF Research Database (Denmark)

    Modrau, Boris; Hjort, Niels; Østergaard, Leif

    2016-01-01

    the collateral supply in acute ischaemic brain tissue and thus facilitate reperfusion despite proximal vessel occlusion. The primary study objective is to evaluate whether theophylline is safe and efficient in acute ischaemic stroke patients as an add-on to thrombolytic therapy.MethodsThe TEA-Stroke Trial...... models, clinical case series and randomized clinical trials are controversial. A Cochrane analysis from 2004 concluded that there was not enough evidence to assess whether theophylline is safe and improves outcomes in patients with acute ischaemic stroke. The TEA-Stroke Trial will clarify whether...

  15. Direct conversion of theophylline to 3-methylxanthine by metabolically engineered E. coli.

    Science.gov (United States)

    Algharrawi, Khalid H R; Summers, Ryan M; Gopishetty, Sridhar; Subramanian, Mani

    2015-12-21

    Methylxanthines are natural and synthetic compounds found in many foods, drinks, pharmaceuticals, and cosmetics. Aside from caffeine, production of many methylxanthines is currently performed by chemical synthesis. This process utilizes many chemicals, multiple reactions, and different reaction conditions, making it complicated, environmentally dissatisfactory, and expensive, especially for monomethylxanthines and paraxanthine. A microbial platform could provide an economical, environmentally friendly approach to produce these chemicals in large quantities. The recently discovered genes in our laboratory from Pseudomonas putida, ndmA, ndmB, and ndmD, provide an excellent starting point for precisely engineering Escherichia coli with various gene combinations to produce specific high-value paraxanthine and 1-, 3-, and 7-methylxanthines from any of the economical feedstocks including caffeine, theobromine or theophylline. Here, we show the first example of direct conversion of theophylline to 3-methylxanthine by a metabolically engineered strain of E. coli. Here we report the construction of E. coli strains with ndmA and ndmD, capable of producing 3-methylxanthine from exogenously fed theophylline. The strains were engineered with various dosages of the ndmA and ndmD genes, screened, and the best strain was selected for large-scale conversion of theophylline to 3-methylxanthine. Strain pDdA grown in super broth was the most efficient strain; 15 mg/mL cells produced 135 mg/L (0.81 mM) 3-methylxanthine from 1 mM theophylline. An additional 21.6 mg/L (0.13 mM) 1-methylxanthine were also produced, attributed to slight activity of NdmA at the N 3 -position of theophylline. The 1- and 3-methylxanthine products were separated by preparative chromatography with less than 5% loss during purification and were identical to commercially available standards. Purity of the isolated 3-methylxanthine was comparable to a commercially available standard, with no contaminant peaks as

  16. Efficacy and side effects of intravenous theophylline in acute asthma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mahemuti G

    2018-01-01

    Full Text Available Gulixian Mahemuti, Hui Zhang, Jing Li, Nueramina Tieliwaerdi, Lili Ren Respiratory Department, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People’s Republic of China Background and objective: Theophylline has been used for decades to treat both acute and chronic asthma. Despite its longevity in the practitioner’s formulary, no detailed meta-analysis has been performed to determine the conditions, including concomitant medications, under which theophylline should be used for acute exacerbations of asthma. We aimed to quantify the usefulness and side effects of theophylline with or without ethylene diamine (aminophylline in acute asthma, with particular emphasis on patient subgroups, such as children, adults, and concomitant medications.Methods: We searched PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, and the WHO Clinical Trials Registry for randomized, controlled clinical trials. We planned a priori subgroup analyses by time post-medication, concomitant medication, control type, and age.Results: We included 52 study arms from 42 individual trials. Of these, 29 study arms included an active control, such as adrenaline, beta-2 agonists, or leukotriene receptor antagonists, and 23 study arms compared theophylline (with or without ethylene diamine with placebo or no drug. Theophylline significantly reduced heart rate when compared with active control (p=0.01 and overall duration of stay (p=0.002, but beta-2 agonists were superior to theophylline at improving forced expiratory volume in one second (FEV1 (p=0.002. Theophylline was not significantly different from other drugs in its effects on respiratory rate, forced vital capacity (FVC, peak expiratory flow rate, admission rate, use of rescue medication, oxygen saturation, or symptom score. Closer examination of the data revealed that the medications given in addition to theophylline or control significantly changed the effectiveness of

  17. Investigating the Potential Effect of Commiphora myrrha on the Pharmacokinetics of Theophylline, a Narrow Therapeutic Index Drug.

    Science.gov (United States)

    Al-Jenoobi, F I; Ahad, A; Raish, M; Al-Mohizea, A M; Alam, M A

    2015-06-01

    The present study was conducted to investigate the effect of commonly used herb Commiphora myrrha on the pharmacokinetic profile of theophylline (narrow therapeutic index drug) in rabbits. In the experimental groups, theophylline (16 mg/kg) was given orally to the rabbits. Where aqueous saline suspension of Commiphora myrrha (176 mg/kg, p.o.), was given to the rabbits and the blood samples were withdrawn at different time intervals (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 h) from marginal ear vein after dosing and theophylline in plasma was analyzed by HPLC method. It was observed that there a significant differences in the Cmax, AUC, AUMC, t1/2, and MRT of theophylline when coadministered with Commiphora myrrha which indicate that the herb affect the metabolism and elimination when coadministered with theophylline. Our results suggested that concurrent use of investigated herb alters the pharmacokinetics of theophylline. Confirmation of these results in human studies will warrant changes in theophylline dose or frequency when coadministered with herb under consideration. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Application of a Physiologically Based Pharmacokinetic Model to Study Theophylline Metabolism and Its Interactions With Ciprofloxacin and Caffeine.

    Science.gov (United States)

    Navid, A; Ng, D M; Wong, S E; Lightstone, F C

    2016-02-01

    Theophylline is a commonly used bronchodilator. However, due to its narrow therapeutic range, moderate elevation of serum concentration can result in adverse drug reactions (ADRs). ADRs occur because of interhuman pharmacokinetic variability and interactions with coprescribed medicines. We developed a physiologically based pharmacokinetic (PBPK) model of theophylline, caffeine, and ciprofloxacin metabolisms to: examine theophylline pharmacokinetic variability, and predict population-level outcomes of drug-drug interactions (DDIs). A simulation-based equation for personalized dosing of theophylline was derived. Simulations of DDI show that calculated personalized doses are safe even after cotreatment with large doses of strong inhibitors. Simulations of adult populations indicate that the elderly are most susceptible to ADRs stemming from theophylline-ciprofloxacin and theophylline-caffeine interactions. Females, especially Asians, due to their smaller average size, are more susceptible to DDI-induced ADRs following typical dosing practices. Our simulations also show that the higher adipose and lower muscle fractions in females significantly alter the pharmacokinetics of theophylline or ciprofloxacin.

  19. Production and characterization of spray-dried theophylline powders prepared from fresh milk for potential use in paediatrics.

    Science.gov (United States)

    Aguiar, João P; Fernandes, Tânia A P; Nese, Carlotta; Fernandes, Ana I; Pinto, João F

    2017-05-01

    This work evaluates the potential of using fresh milk to deliver theophylline to children. Theophylline-fresh milk systems were prepared using different solids ratios (0 : 1-1 : 0) and three fat contents in commercial milks (low, medium and high), which were spray-dried at different inlet air temperatures (Tinlet - 105, 130 and 150 °C). The process was evaluated for yield and the resulting powders for moisture content (MC), particle size and shape, density and wettability. Theophylline-milk potential interactions (differential scanning calorimetry (DSC) and FT-IR) and chemical (theophylline content) and microbiological stability of powders (shelf and in-use) were also evaluated. The production yield (13.6-76.0%), MC (0.0-10.3%) and contact angles in water (77.29-93.51°) were significantly (P Theophylline content remained stable after 6 months of storage, before extemporaneous reconstitution. After reconstitution in water, low-fat milk samples (stored at 4 °C) met the microbial pharmacopoeia criteria for up to 7 days. No theophylline-milk components interaction was observed. Spray-dried milk-composed powders may be used as vehicles for theophylline delivery in paediatrics following further characterization and in-vivo evaluation. © 2016 Royal Pharmaceutical Society.

  20. Case Report: The risks associated with chronic theophylline therapy and measures designed to improve monitoring and management.

    Science.gov (United States)

    Hopkins, Michael E; MacKenzie-Ross, Robert V

    2016-03-05

    Symptoms of theophylline toxicity and factors that augment the risk of developing it are well documented in the literature. However these appear to be poorly considered in clinical practice. This case underlines the challenges in recognising and managing theophylline toxicity; moreover the requirement for improved application of knowledge of its pharmacokinetics to our practice. In this case we observe how theophylline toxicity can be overlooked due to the presence of non-specific symptoms and lack of a structured system to mitigate error in detection, in both hospital medicine and general practice. Here, the initial theophylline concentration measurement was documented as 59.3 mg/l in a patient taking the medication long-term, with the previous concentration being recorded one year prior. Management consisted of suspension of theophylline along with best supportive care, however in the process other conditions were exacerbated and the patient ultimately died in hospital. Congestive cardiac failure, congestive liver disease and polypharmacy were factors isolated from this case that expedited the patients' development of theophylline toxicity. This was perpetuated by delay in diagnosis due to presentation with generalised symptoms including tachycardia, vomiting and neurological symptoms. Findings from this case necessitate a requirement for more stringent monitoring of theophylline when taken chronically in those who demonstrate risk factors for toxicity. This would aim to prevent accumulation of the drug, toxicity onset and subsequent acute presentation to hospital. Intervention, through charcoal haemoperfusion may provide a means of enhanced recovery to reduce sequelae of toxicity.

  1. Modeling of drug release from multi-unit dosage tablets of theophylline

    African Journals Online (AJOL)

    SERVER

    2007-11-19

    Nov 19, 2007 ... A model of multi-unit dose tablets of theophylline (dose, 600 mg) has been designed to give a prompt release dose (200 mg) in the first 1 h and the remaining sustained release ... granules, microcapsules or microparticles of the same drug but of different release profiles. They are normally formulated into a ...

  2. Pharmacokinetics of the cytochrome P-450 substrates phenytoin, theophylline, and diazepam in healthy Greyhound dogs

    Science.gov (United States)

    KuKanich, Butch; Nauss, Jon L

    2011-01-01

    The purpose of this study was to determine the pharmacokinetics of phenytoin, theophylline, and diazepam in six healthy Greyhound dogs. Additionally the pharmacokinetics of the diazepam metabolites oxazepam and nordiazepam after diazepam administration were determined. Phenytoin sodium (12 mg/kg), aminophylline (10 mg/kg), and diazepam (0.5 mg/kg) were administered IV on separate occasions and blood obtained at predetermined time points for the quantification of plasma drug concentrations by florescence polarization immunoassay (phenytoin, theophylline) or mass spectrometry (diazepam, oxazepam, nordiazepam). The terminal half-life was 4.9, 9.2, and 1.0 hours, respectively for phenytoin, theophylline, and diazepam, and 6.2 and 2.4 hours for oxazepam and nordiazepam after IV diazepam. The clearance was of 2.37, 0.935, and 27.9 mL/min/kg respectively for phenytoin, theophylline, and diazepam. The CMAX was 44.7 and 305.2 ng/mL for oxazepam and nordiazepam, respectively, after diazepam administration. Temazepam was not detected above 5 ng/mL in any sample after IV diazepam. PMID:21692812

  3. [Severe felodipine and theophylline poisoning successfully treated by 4-aminopyridine: a case report].

    Science.gov (United States)

    Magdalan, Jan; Kochman, Krystyna; Smolarek, Małgorzata; Przewłocki, Michal; Antończyk, Andrzej

    2003-01-01

    The case of a 51-year-old man who ingested 100 mg of felodipine (Plendil, 20 tablets á 5 mg) and 9 g of theophylline (Theospirex retard, 30 tablets á 300 mg) is presented. The patient developed severe hypotension, tachycardia, circulatory insufficiency and paralytic ileus. No ECG effects were observed. Although felodipine led to a reduction in the bioability of theophylline, the serum theophylline concentration 15 h after the admission was 92 mg/L (the therapeutic concentration of theophylline 10-20 mg/L). The protracted hypotension did not respond to vasopressor and calcium therapy. The addition of 4-aminopyridine (4-AP) infusion resulted in fast receding of poisoning symptoms: increase of blood pressure, receding of circulatory insufficiency and metabolic acidosis, and return of peristalsis. This case suggests the usefulness of 4-AP in the treatment of poisoning by dihydropyridine derivatives. However, confirmation of the effectiveness of this substance for pharmacotherapy of dihydrophyridine derivatives poisoning requires further clinical research. The influence of 4-AP on calcium channels is indirect. It blocks potassium channels K1 in cytoplasm side which makes potassium stay inside the cell leading to depolarisation and opening of voltage-dependent calcium channels.

  4. EFFECT OF CRYOPRESERVATION AND THEOPHYLLINE ON MOTILITY CHARACTERISTICS OF LAKE STURGEON (ACIPENSER FULVESCENS) SPERMATOZOA

    Science.gov (United States)

    Computer-assisted motility analysis (CASA) was used to evaluate the effect of cryopreservation and theophylline treatment on sperm motility of lake sturgeon (Acipenser fulvescens).Motility was recorded at 0 and 5 min postactivation.The effect of cryopreservation on sperm acrosin-...

  5. Theophylline Population Pharmacokinetics and Dosing in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.

    Science.gov (United States)

    Frymoyer, Adam; Su, Felice; Grimm, Paul C; Sutherland, Scott M; Axelrod, David M

    2016-09-01

    Children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) frequently develop acute kidney injury due to renal ischemia. Theophylline, which improves renal perfusion via adenosine receptor inhibition, is a potential targeted therapy. However, children undergoing cardiac surgery and CPB commonly have alterations in drug pharmacokinetics. To help understand optimal aminophylline (salt formulation of theophylline) dosing strategies in this population, a population-based pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM) from 71 children (median age 5 months; 90% range 1 week to 10 years) who underwent cardiac surgery requiring CPB and received aminophylline as part of a previous randomized controlled trial. A 1-compartment model with linear elimination adequately described the pharmacokinetics of theophylline. Weight scaled via allometry was a significant predictor of clearance and volume. In addition, allometric scaled clearance increased with age implemented as a power maturation function. Compared to prior reports in noncardiac children, theophylline clearance was markedly reduced across age. In the final population pharmacokinetic model, optimized empiric dosing regimens were developed via Monte Carlo simulations. Doses 50% to 75% lower than those recommended in noncardiac children were needed to achieve target serum concentrations of 5 to 10 mg/L. © 2016, The American College of Clinical Pharmacology.

  6. Response Surface Optimization for Decaffeination and Theophylline Production by Fusarium solani.

    Science.gov (United States)

    Nanjundaiah, Shwetha; Bhatt, Praveena; Rastogi, Navin Kumar; Thakur, Munna Singh

    2016-01-01

    Coffee processing industries generate caffeine-containing waste that needs to be treated and decaffeinated before being disposed. Five fungal isolates obtained on caffeine-containing mineral media were tested for their ability to utilize caffeine at high concentrations. An isolate identified as Fusarium solani could utilize caffeine as a sole source of carbon and nitrogen up to 5 g/l and could degrade it to an extent of 30-53 % in 120 h. Sucrose that was added as an auxiliary substrate (5 g/l) enhanced the biodecaffeination of caffeine to 88 % in 96 h. The addition of co- substrate (sucrose) not only resulted in higher biodecaffeination efficiency, but also reduced the incubation period from the initial 120 to 96 h. Theophylline and 3-methyl xanthine were obtained as the major metabolites of decaffeination at 96 and 120 h, respectively. Response surface methodology used to optimize the process parameters for maximum biodecaffeination as well as theophylline production showed that a pH of 5.8, temperature of 24 °C and inoculum size of 4.8 × 10(5) spores/ml have resulted in a complete biodecaffeination of caffeine as well as the production of theophylline with a yield of 33 % (w/w). Results thus show that a viable and sustainable process can be developed for the detoxification of caffeine along with the recovery of theophylline, a commercially important chemical.

  7. Three-dimensional model of a selective theophylline-binding RNA molecule

    Energy Technology Data Exchange (ETDEWEB)

    Tung, Chang-Shung; Oprea, T.I.; Hummer, G.; Garcia, A.E.

    1995-07-01

    We propose a three-dimensional (3D) model for an RNA molecule that selectively binds theophylline but not caffeine. This RNA, which was found using SELEX [Jenison, R.D., et al., Science (1994) 263:1425] is 10,000 times more specific for theophylline (Kd=320 nM) than for caffeine (Kd=3.5 mM), although the two ligands are identical except for a methyl group substituted at N7 (present only in caffeine). The binding affinity for ten xanthine-based ligands was used to derive a Comparative Molecular Field Analysis (CoMFA) model (R{sup 2} = 0.93 for 3 components, with cross-validated R{sup 2} of 0.73), using the SYBYL and GOLPE programs. A pharmacophoric map was generated to locate steric and electrostatic interactions between theophylline and the RNA binding site. This information was used to identify putative functional groups of the binding pocket and to generate distance constraints. Based on a model for the secondary structure (Jenison et al., idem), the 3D structure of this RNA was then generated using the following method: each helical region of the RNA molecule was treated as a rigid body; single-stranded loops with specific end-to-end distances were generated. The structures of RNA-xanthine complexes were studied using a modified Monte Carlo algorithm. The detailed structure of an RNA-ligand complex model, as well as possible explanations for the theophylline selectivity will be discussed.

  8. Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state.

    Directory of Open Access Journals (Sweden)

    Becka M Warfield

    Full Text Available RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are

  9. Molecular simulations and Markov state modeling reveal the structural diversity and dynamics of a theophylline-binding RNA aptamer in its unbound state.

    Science.gov (United States)

    Warfield, Becka M; Anderson, Peter C

    2017-01-01

    RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are present the population

  10. PILOT STUDY: An international comparison of mass fraction purity assignment of theophylline: CCQM Pilot Study CCQM-P20.e (Theophylline)

    Science.gov (United States)

    Westwood, S.; Josephs, R.; Daireaux, A.; Wielgosz, R.; Davies, S.; Kang, M.; Ting, H.; Phillip, R.; Malz, F.; Shimizu, Y.; Frias, E.; Pérez, M.; Apps, P.; Fernandes-Whaley, M.; DeVos, B.; Wiangnon, K.; Ruangrittinon, N.; Wood, S.; Duewer, D.; Schantz, M.; Bedner, M.; Hancock, D.; Esker, J.

    2009-01-01

    Under the auspices of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a laboratory comparison, CCQM-P20.e, was coordinated by the Bureau International de Poids et Mesures (BIPM) in 2006/2007. Nine national measurement institutes, two expert laboratories and the BIPM participated in the comparison. Participants were required to assign the mass fraction of theophylline present as the main component in two separate study samples (CCQM-P20.e.1 and CCQM-P20.e.2). CCQM-P20.e.1 consisted of a high-purity theophylline material obtained from a commercial supplier. CCQM-P20.e.2 consisted of theophylline to which known amounts of the related structure compounds theobromine and caffeine were added in a homogenous, gravimetrically controlled fashion. For the CCQM-P20.e.2 sample it was possible to estimate gravimetric reference values both for the main component and for the two spiked impurities. In addition to assigning the mass fraction content of theophylline for both materials, participants were requested but not obliged to provide mass fraction estimates for the minor components they identified in each sample. The results reported by the study participants for the mass fraction content of theophylline in both materials showed good levels of agreement both with each other and with the gravimetric reference value assigned to the CCQM-P20.e.2 material. There was also satisfactory agreement overall, albeit at higher levels of uncertainty, in the quantification data reported for the minor components present in both samples. In the few cases where a significant deviation was observed from the consensus values reported by the comparison participants or gravimetric reference values where these where available, they appeared to arise from the use of non-optimal chromatographic separation conditions. The results demonstrate the feasibility for laboratories to assign mass fraction content with associated absolute expanded

  11. Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Randles, J.; Kimmich, G.A.

    1978-01-01

    Phloretin and theophylline each exert an immediate inhibitory effect on the Na/sup +/-independent, facilitated-diffusion transport system for sugar associated with intestinal epithelial cells. Phloretin inhibits approximately 50% more of the total Na/sup +/-independent sugar flux than theophylline. Neither agent has an immediate effect on the Na/sup +/-dependent, concentrative sugar transport system, although preincubation of the cells with phloretin causes a significant inhibition. The slowly developing effect is correlated with a decrease in cellular adenosine triphosphate (ATP) and an evaluation of intracellular Na/sup +/. Other agents which elevate cell Na/sup +/ also inhibit Na/sup +/-dependent sugar influx, even if ATP levels are not depleted. On the other hand, if ATP is depleted by phloretin under conditions in which the cells do not gain Na/sup +/, the inhibitory effect on Na/sup +/-dependent sugar flux tends to disappear. The slow-onset phloretin effects are due to transinhibition of the Na/sup +/-dependent sugar carrier by cellular Na/sup +/. When the passive sugar carrier is inhibited by phloretin or theophylline, the concentrative system can establish an enhanced sugar gradient. Because of the secondary metabolic effects of phloretin, theophylline induces a greater gradient enhancement despite its more limited effect on the passive sugar-transport system. Sugar gradients as large as 20-fold are induced by theophylline, in contrast to 12-fold gradients observed in the presence of phloretin and approximately 7- to 8-fold for untreated cells. These results are discussed in terms of conceptual questions regarding the energetics of Na/sup +/-dependent transport systems.

  12. Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Randles, J.; Kimmich, G.A.

    1978-03-01

    Phloretin and theophylline each exert an immediate inhibitory effect on the Na/sup +/-independent, facilitated-diffusion transport system for sugar associated with intestinal epithelial cells. Phloretin inhibits approximately 50% more of the total Na/sup +/-independent sugar flux than theophylline. Neither agent has an immediate effect on the Na/sup +/-dependent, concentrative sugar transport system, although preincubation of the cells with phloretin causes a significant inhibition. The slowly developing effect is correlated with a decrease in cellular adenosine triphosphate (ATP) and an elevation of intracellular Na/sup +/. Other agents which elevate cell Na/sup +/ also inhibit Na/sup +/-dependent sugar influx, even if ATP levels are not depleted. On the other hand, if ATP is depleted by phloretin under conditions in which the cells do not gain Na/sup +/, the inhibitory effect on Na/sup +/-dependent sugar flux tends to disappear. The slow-onset phloretin effects are due to transinhibition of the Na/sup +/-dependent sugar carrier by cellular Na/sup +/. When the passive sugar carrier is inhibited by phloretin or theophylline, the concentrative system can establish an enhanced sugar gradient. Because of the secondary metabolic effects of phloretin, theophylline induces a greater gradient enhancement despite its more limited effect on the passive sugar-transport system. Sugar gradients as large as 20-fold are induced by theophylline, in contrast to 12-fold gradients observed in the presence of phloretin and approximately 7- to 8-fold for untreated cells. These results are discussed in terms of conceptual questions regarding the energetics of Na/sup +/-dependent transport systems.

  13. Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis.

    Science.gov (United States)

    Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

    2016-05-01

    Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003). This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  14. Effects of Theophylline with Methylprednisolone Combination Therapy on Biomechanics and Histopathology in Diaphragm Muscles of Rats.

    Science.gov (United States)

    Yuzkat, Nureddin; Kati, Ismail; Isik, Yasemin; Kavak, Servet; Goktas, Ugur; Cengiz, Nurettin

    2016-10-01

    The purpose of this study was to investigate the effects of theophylline and methylprednisolone on the mechanical response and histopathology of hemidiaphragm muscle in rats. In the current study, we aimed to investigate the effects of theophylline and methylprednisolone, which are frequently used in clinics and which have different effects on the respiratory system and on the biomechanics and histopathology of the diaphragm muscle. The study included four groups of rats. Group T received 1 mg/kg of intraperitoneal theophylline, group M received 2 mg/kg of intraperitoneal methylprednisolone, group TM received 1 mg/kg of intraperitoneal theophylline plus 2 mg/kg of intraperitoneal methylprednisolone, and group K received of 1 mL intraperitoneal isotonic solution (of 0.9 % NaCl). The medications were continued for 7 days in each group. The rats underwent cervical dislocation under anesthesia on the eighth day, and their diaphragm samples were extracted. The left hemidiaphragm was used for the investigation of biomechanical parameters, and the right hemidiaphragm was used for the histopathological evaluation. It was observed that the medication administered in group T increased the contraction strength and duration compared with that in group M. Additionally, the duration of semi-relaxation was prolonged in group T compared with group M. The highest contraction strength and the longest contraction period among all of the groups were observed in group TM. It was concluded that the combined use of theophylline and methylprednisolone had positive effects on the contraction strength and the durations of contraction and semi-relaxation of the diaphragm muscle. In addition, both drugs had synergistic effects on each other.

  15. Long-term administration of theophylline and glucose recovery after hypoglycaemia in patients with type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Hvidberg, A; Rosenfalck, A; Christensen, N J

    1998-01-01

    The methylxanthine theophylline increases intrahepatic c-AMP and c-AMP mediates the hepatic glucose response to adrenaline and glucagon. Intravenous theophylline increases glucose recovery during acute insulin-induced hypoglycaemia and caffeine increases hypoglycaemia awareness and glucoregulatory...... hormone secretion. In this study we tested the hypothesis that long-term administration of theophylline might augment glucose recovery after insulin-induced hypoglycaemia. Eleven healthy subjects and 8 patients with Type 1 diabetes mellitus were made hypoglycaemic by 60 min insulin infusion (40 mU m(-2......)) after 2 weeks' oral therapy with Euphyllin Retard (theophylline) or placebo. Plasma glucose nadir was 2.54 (2.31-2.77) mmol l(-1) after Euphyllin Retard and 2.27 (2.05-2.48) mmol l(-1) after placebo (mean difference 0.26 (0.05-0.58) mmol l(-1), p = 0.09) for healthy control subjects and 2.56 (2...

  16. Theophylline therapy for Cheyne-Stokes respiration during sleep in a 41-year-old man with refractory arterial hypertension.

    Science.gov (United States)

    Wolf, Jacek; Świerblewska, Ewa; Jasiel-Wojculewicz, Hanna; Gockowski, Krzysztof; Wyrzykowski, Bogdan; Somers, Virend K; Narkiewicz, Krzysztof

    2014-07-01

    We report a case of a 41-year-old man who was noted to have position-dependent Cheyne-Stokes respiration with central sleep apnea (CSA) during sleep. The patient had multiple cardiovascular risk factors and target organ damages, including a history of two myocardial infarctions, transient ischemic attack, and chronic kidney disease. His hypertension was refractory to a number of antihypertensive medicines, however, a complete elimination of sleep-disordered breathing with oral theophylline treatment was paralleled by a significant BP fall with a subsequent need for reduction of antihypertensive drugs. Following these surprising observations we decided to withdraw theophylline from treatment (in-clinic). Theophylline discontinuation resulted in a gradual increase in BP and an urgent call for antihypertensive treatment modification. These observations suggest a potent hypotensive action of oral theophylline via Cheyne-Stokes respiration with CSA elimination. Our data suggest that CSA may be a mechanism that raises BP even during the daytime.

  17. REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY STUDY OF LIPOPHILICITY OF IMIDAZO[2,1-F]THEOPHYLLINE DERIVATIVES.

    Science.gov (United States)

    Zagórska, Agnieszka; Czopek, Anna; Pełka, Karolina; Bajda, Marek; Stanisz-Wallis, Krystyna; Pawłowski, Maciej

    2015-01-01

    The present study is a part of our physicochemical and pharmacological studies in a group of tricyclic theophylline derivatives. The investigated compounds exhibit different pharmacological profiles in comparison to theophylline and have been tested as potential antidepressant and/or antipsychotic agents. The differences in pharmacological action between theophylline and their tricyclic derivatives can be explained by their various physicochemical properties, especially lipophilicity. The chromatographic behavior of twenty three derivatives of imidazo[2,1-ƒ]theophylline was investigated, using reversed-phase high performance liquid chromatography (RP-HPLC) method. Moreover, partition coefficients and selected pharmacokinetic parameters were calculated computationally. Principal component analysis (PCA) method was used to establish the relationship between obtained experimental and computational parameters.

  18. In vitro release of theophylline from starch-based matrices prepared via high hydrostatic pressure treatment and autoclaving.

    Science.gov (United States)

    Błaszczak, Wioletta; Buciński, Adam; Górecki, Adrian R

    2015-03-06

    Recent works have demonstrated that release behavior of bioactive compounds varies with the nature of the matrix regarding its chemical composition, morphology and surface properties. Starch matrices varying in amylose content (maize, sorghum, Hylon VII) or pure amylopectin ones (waxy maize, amaranth starch), containing theophylline (10 mg, 50 mg/0.5 g of starch), were obtained via high hydrostatic pressure treatment (650 MPa/9 min) and autoclaving (120 °C/20 min). Both the treatment used and drug dose affected the theophylline release profiles from the matrices studied. The profiles of amylopectin starch matrices satisfactorily fitted with selected mathematical models, indicating a controlled theophylline release. The principal component analysis confirmed substantial differences in drug release between the amylose and amylopectin matrices. The differences in matrix morphology, internal surface area and porosity (mesopore diameter, cumulative pore volume) between the matrices studied were found to be key factors affecting the theophylline dissolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Theophylline-induced respiratory recovery following cervical spinal cord hemisection is augmented by serotonin 2 receptor stimulation.

    Science.gov (United States)

    Basura, Gregory J; Nantwi, Kwaku D; Goshgarian, Harry G

    2002-11-22

    Cervical spinal cord hemisection leads to a disruption of bulbospinal innervation of phrenic motoneurons resulting in paralysis of the ipsilateral hemidiaphragm. We have previously demonstrated separate therapeutic roles for theophylline, and more recently serotonin (5-HT) as modulators to phrenic nerve motor recovery; mechanisms that likely occur via adenosine A1 and 5-HT2 receptors, respectively. The present study was designed to specifically determine if concurrent stimulation of 5-HT2 receptors may enhance motor recovery induced by theophylline alone. Adult female rats (250-350 g; n=7 per group) received a left cervical (C2) hemisection that resulted in paralysis of the ipsilateral hemidiaphragm. Twenty-four hours later rats were given systemic theophylline (15 mg/kg, i.v.), resulting in burst recovery in the ipsilateral phrenic nerve. Theophylline-induced recovery was enhanced with the 5-HT2A/2C receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI; 1.0 mg/kg). DOI-evoked augmentation of theophylline-induced recovery was attenuated following subsequent injection of the 5-HT2 receptor antagonist, ketanserin (2.0 mg/kg). In a separate group, rats were pretreated with ketanserin, which did not prevent subsequent theophylline-induced respiratory recovery. However, pretreatment with ketanserin did prevent DOI-induced augmentation of the theophylline-evoked phrenic nerve burst recovery. Lastly, using immunocytochemistry and in situ hybridization, we showed for the first time a positive co-localization of adenosine A1 receptor mRNA and immunoreactivity with phrenic motoneurons of the cervical ventral horns. Taken together, the results of the present study suggest that theophylline may induce motor recovery likely at adenosine A1 receptors located at the level of the spinal cord, and the concurrent stimulation of converging 5-HT2 receptors may augment the response.

  20. THE INFLUENCE OF TREATMENT WITH THEOPHYLLINE ON MITOTIC DIVISIONS AND ON GROWTH OF PLANTLES AT CAPSICUM ANNUUM L.

    OpenAIRE

    Mihaela Balan; Ioan Bara; Elena Cristina Rosu

    2007-01-01

    This papers presents, the theophylline effects on mitotic division of roots at Capsicum annuum L., and the growth of plantlets after the treatment. The treatment has induced the decrease of the mitotic index, until total inhibitions at maxim variant of treatment (0,25% theophylline), and numerous aberations types in anaphases and thelophases. About the growth of plantles, the treatment has stimulated theirs growth, mostly on theirs roots.

  1. Improved smell function with increased nasal mucus sonic hedgehog in hyposmic patients after treatment with oral theophylline.

    Science.gov (United States)

    Henkin, Robert I; Hosein, Suzanna; Stateman, William A; Knöppel, Alexandra B; Abdelmeguid, Mona

    We previously demonstrated the presence of sonic hedgehog (Shh) in nasal mucus in normal subjects and in patients with smell loss (hyposmia). Nasal mucus Shh levels were found significantly diminished in untreated hyposmic patients of multiple etiologies. Since treatment with oral theophylline has been previously associated with improvement in smell function we wished to study if such treatment increased nasal mucus Shh as well as improved smell function in patients with hyposmia. Forty-four patients with hyposmia of several etiologies were evaluated for changes in hyposmia by subjective measurements of smell, taste and flavor perception and by olfactometry. Measurements of nasal mucus Shh were made in relationship to each set of sensory measurements. Patients were treated with oral theophylline at doses of 200-800mg for periods of 2-10months with sensory function, nasal mucus Shh and serum theophylline levels evaluated at these time intervals. Nasal mucus Shh measurements were made with a sensitive spectrophotometric ELISA assay and theophylline with a fluorometric assay. There was consistent, significant improvement in subjective responses in smell, taste and flavor perception and in olfactometry associated with increased nasal mucus Shh and serum theophylline after theophylline treatment. Improvement in smell function and in nasal mucus Shh was positively correlated in a dose-response relationship after treatment with oral theophylline. Results are consistent with a successful role for theophylline in improvement of smell function in hyposmic patients of multiple etiologies associated with increased nasal mucus Shh which can act as a biochemical marker for smell function. Copyright © 2016. Published by Elsevier Inc.

  2. The effects of theophylline on hospital admissions and exacerbations in COPD patients: audit data from the Bavarian disease management program.

    Science.gov (United States)

    Fexer, Johannes; Donnachie, Ewan; Schneider, Antonius; Wagenpfeil, Stefan; Keller, Manfred; Hofmann, Frank; Mehring, Michael

    2014-04-25

    Theophylline is often used to treat chronic obstructive pulmonary disease (COPD). Current evidence leaves the effectiveness and safety of this drug open to question. Thus, we evaluated the effectiveness of theophylline on the rate of hospitalizations and disease exacerbations by examining routine data from the ambulatory disease management program for COPD in the German state of Bavaria. Data sets from a total of 30 330 patients were examined. Logistic regression models were used to calculate propensity scores that controlled for baseline characteristics. These propensity scores, in turn, were used to create comparable patient groups, which were observed for a median follow-up time of 9 quarters (the theophylline group) and 10 quarters (the control group). 1496 patients with first prescription of theophylline were matched with 1496 patients with no record of theophylline treatment. 1. The probability of suffering an exacerbation during the period of observation, was 33.5% for the control group and 43.4% for the theophylline group [hazard ratio (HR) 1.41; 95% confidence interval (CI) 1.24 to 1.60], yielding a number needed to harm (NNH) of 11 (95% CI 7.7 to 20.9). The probability for hospitalization was 11.4% for the control group and 17.4% of the theophylline group (HR 1.61; 95% CI 1.29 to 2.01), yielding a NNH of 17 (95%CI 11.0-34.5). Treatment with theophylline is associated with an elevated incidence of exacerbations and hospitalizations. The therapeutic value of this drug should be reconsidered and investigated in further studies.

  3. Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma.

    Science.gov (United States)

    Tee, A K H; Koh, M S; Gibson, P G; Lasserson, T J; Wilson, A J; Irving, L B

    2007-07-18

    Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma. We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006. All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist. In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information. Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14

  4. Theophylline, adenosine receptor antagonist prevents behavioral, biochemical and neurochemical changes associated with an animal model of tardive dyskinesia.

    Science.gov (United States)

    Bishnoi, Mahendra; Chopra, Kanwaljit; Kulkarni, Shrinivas K

    2007-01-01

    Tardive dyskinesia is considered to be the late onset adverse effect of prolonged administration of typical neuroleptic drugs. Adenosine is now widely accepted as the major inhibitory neuromodulators in the central nervous system besides GABA. Antagonists of A2A receptors are known to confer protection against neuronal damage caused by toxins and reactive oxygen species. The present study investigated the effect of adenosine receptor antagonist, theophylline (25 and 50 mg/kg, ip) in an animal model of tardive dyskinesia by using different behavioral (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase)) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg ip for 21 days) significantly increased vacuous chewing movements (VCMs), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by theophylline. Chronic administration of haloperidol also resulted in the increased dopamine receptor sensitivity as evidenced by increased locomotor activity and stereotypic rearing. Further, it also decreased % retention time in elevated plus maze paradigm. Pretreatment with theophylline reversed these behavioral changes. Chronic administration of haloperidol also induced oxidative damage in all the brain regions which was prevented by theophylline, especially in the striatum. Chronic administration of haloperidol resulted in a decrease in dopamine levels which was reversed by treatment with theophylline (at higher doses). The findings of the present study suggested the involvement of adenosinergic receptor system in the development of tardive dyskinesia and possible therapeutic potential of theophylline in this disorder.

  5. A simple HPLC-UV method for the quantification of theophylline in rabbit plasma and its pharmacokinetic application.

    Science.gov (United States)

    Al-Jenoobi, Fahad I; Ahad, Abdul; Mahrous, Gamal M; Raish, Mohammad; Alam, Mohd Aftab; Al-Mohizea, Abdullah M

    2015-01-01

    A simple, precise and accurate high-performance liquid chromatography-ultraviolet method was developed and validated for the quantification of theophylline in rabbit plasma using hydroxyethyl theophylline as an internal standard. Separation was performed on Waters(®) C18 column (µBondapak™ 5 µm, 150 × 3.9 mm) using a mobile phase consisting of water-acetonitrile (96:4 v/v) at a flow rate of 1 mL/min. Validation of the method was performed in order to demonstrate its selectivity, linearity, precision, accuracy and stability. The calibration curves of theophylline were linear over a concentration range of 0.1-25 µg/mL. The within- and between-day coefficient of variation (CV) were theophylline at the three levels of quality control samples were 63.1, 69.4 and 69.7%. The method was rapid with retention time of theophylline and the internal standard observed at ∼5.2 and 6.5 min, respectively. The developed method was applied successfully for studying the pharmacokinetics of theophylline in rabbits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Treating perinatal asphyxia with theophylline at birth helps to reduce the severity of renal dysfunction in term neonates.

    Science.gov (United States)

    Raina, Alok; Pandita, Aakash; Harish, Rekha; Yachha, Monika; Jamwal, Ashu

    2016-10-01

    Perinatal asphyxia is a common neonatal problem and contributes significantly to neonatal morbidity and mortality. This study was designed to determine whether theophylline could prevent or ameliorate renal dysfunction in term neonates with perinatal asphyxia. We randomised 159 severely asphyxiated term newborns to receive a single dose of 5 mg/kg intravenous theophylline (n = 78) or a placebo (n = 81) during the first hour of life. The infant's 24-hour fluid intake, urine volume, serum creatinine, creatinine clearance and sodium excretion were recorded during days one, three and five of life, starting 12 hours after the theophylline or placebo infusion. Neonates in the theophylline group had lower serum creatinine levels (0.83 ± 0.35 versus 1.47 ± 0.61; p = 0.00) and higher endogenous creatinine clearance (32.16 ± 16.34 versus 17.73 ± 7.92; p = 0.00) than the placebo group. Severe renal dysfunction, namely acute kidney injury, was present in 36 (15%) of the neonates in the theophylline group versus 117 (48%) in the placebo group (p theophylline administered to term neonates with perinatal asphyxia within the first hour of life significantly decreased serum creatinine levels and significantly increased creatinine clearance. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  7. Bronchodilator and Anti-Inflammatory Action of Theophylline in a Model of Ovalbumin-Induced Allergic Inflammation.

    Science.gov (United States)

    Urbanova, A; Kertys, M; Simekova, M; Mikolka, P; Kosutova, P; Mokra, D; Mokry, J

    2016-01-01

    Phosphodiesterases (PDEs) represent a super-family of 11 enzymes hydrolyzing cyclic nucleotides into inactive 5' monophosphates. Inhibition of PDEs leads to a variety of cellular effects, including airway smooth muscle relaxation, inhibition of cellular inflammation, and immune responses. In this study we focused on theophylline, a known non-selective inhibitor of PDEs. Theophylline has been used for decades in the treatment of chronic inflammatory airway diseases. It has a narrow therapeutic window and belongs to the drugs whose plasma concentration should be monitored. Therefore, the main goal of this study was to evaluate the plasma theophylline concentration and to determine its relevance to pharmacological effects after single and longer term (7 days) administration of theophylline at different doses (5, 10, 20, and 50 mg/kg) in guinea pigs. Airway hyperresponsiveness was assessed by repeated exposure to ovalbumin. Theophylline reduced specific airway resistance in response to histamine nebulization, measured in a double chamber body plethysmograph. A decrease in tracheal smooth muscle contractility after cumulative doses of histamine and acetylcholine was confirmed in vitro. A greater efficacy of theophylline after seven days long treatment indicates the predominance of its anti-inflammatory activity, which may be involved in the bronchodilating action.

  8. Comparative analysis of theophylline and cholera toxin in rat colon reveals an induction of sealing tight junction proteins.

    Science.gov (United States)

    Markov, Alexander G; Falchuk, Evgeny L; Kruglova, Natalia M; Rybalchenko, Oksana V; Fromm, Michael; Amasheh, Salah

    2014-11-01

    Claudin tight junction proteins have been identified to primarily determine intestinal epithelial barrier properties. While functional contribution of single claudins has been characterized in detail, information on the interplay with secretory mechanisms in native intestinal epithelium is scarce. Therefore, effects of cholera toxin and theophylline on rat colon were analyzed, including detection of sealing claudins. Tissue specimens were stripped off submucosal tissue layers and mounted in Ussing chambers, and short-circuit current (ISC) and transepithelial resistance (TER) were recorded. In parallel, expression and localization of claudins was analyzed and histological studies were performed employing hematoxylin-eosin staining and light and electron microscopy. Theophylline induced a strong increase of ISC in colon tissue specimens. In parallel, a decrease of TER was observed. In contrast, cholera toxin did not induce a significant increase of ISC, whereas an increase of TER was detected after 120 min. Western blots of membrane fractions revealed an increase of claudin-3 and -4 after incubation with cholera toxin, and theophylline induced an increase of claudin-4. In accordance, confocal laser-scanning microscopy exhibited increased signals of claudin-3 and -4 after incubation with cholera toxin, and increased signals of claudin-4 after incubation with theophylline, within tight junction complexes. Morphological analyses revealed no general changes of tight junction complexes, but intercellular spaces were markedly widened after incubation with cholera toxin and theophylline. We conclude that cholera toxin and theophylline have different effects on sealing tight junction proteins in native colon preparations, which may synergistically contribute to transport functions, in vitro.

  9. Plasma concentrations of the cyclic nucleotides, adenosine 3',5'-monophosphate and guanosine 3'.5'-monophosphate, in healthy adults treated with theophylline

    DEFF Research Database (Denmark)

    Fenger, M; Eriksen, P B; Nielsen, M K

    1982-01-01

    Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine...... monophosphate concentrations decreased by 29% on average when theophylline was administered. The change in cyclic guanosine monophosphate was not correlated to the plasma concentration of theophylline in the range studied....

  10. Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma.

    Science.gov (United States)

    Moon, Hyung-Geun; Kim, You-Sun; Choi, Jun-Pyo; Choi, Dong-Sic; Yoon, Chang Min; Jeon, Seong Gyu; Gho, Yong Song; Kim, Yoon-Keun

    2010-01-31

    Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung inflammation partly induced by Th1 immune response. ASA attenuated the beneficial effects of theophylline. However, co-administration of the ASA metabolite salicylic acid (SA) showed no attenuating effect on theophylline treatment. The therapeutic effect of theophylline was associated with increase in cAMP levels, which was blocked by co-treatment of theophylline and ASA. ASA co-treatment also attenuated the anti-inflammatory effects of a specific phosphodiesterase 4 inhibitor. These results demonstrate that ASA reverses anti-inflammatory effects of theophylline, and that ASA exerts its adverse effects through the inhibition of cAMP production. Our data suggest that ASA reverses lung inflammation in patients taking theophylline, although clinical evidence will be needed.

  11. Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma

    Science.gov (United States)

    Moon, Hyung-Geun; Kim, You-Sun; Choi, Jun-Pyo; Choi, Dong-Sic; Yoon, Chang Min; Jeon, Seong Gyu

    2010-01-01

    Theophylline is commonly used to treat severe asthma and chronic obstructive pulmonary disease (COPD) characterized by non-eosinophilic inflammation. Acetyl salicylic acid (ASA) is one of the most widely used medications worldwide, but up to 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma. A non-eosinophilic asthma mouse model was induced by airway sensitization with lipopolysaccharide-containing allergen and then challenged with allergen alone. Therapeutic intervention was performed during allergen challenge. Theophylline inhibited lung inflammation partly induced by Th1 immune response. ASA attenuated the beneficial effects of theophylline. However, co-administration of the ASA metabolite salicylic acid (SA) showed no attenuating effect on theophylline treatment. The therapeutic effect of theophylline was associated with increase in cAMP levels, which was blocked by co-treatment of theophylline and ASA. ASA co-treatment also attenuated the anti-inflammatory effects of a specific phosphodiesterase 4 inhibitor. These results demonstrate that ASA reverses anti-inflammatory effects of theophylline, and that ASA exerts its adverse effects through the inhibition of cAMP production. Our data suggest that ASA reverses lung inflammation in patients taking theophylline, although clinical evidence will be needed. PMID:19887894

  12. Plasma concentrations of the cyclic nucleotides, adenosine 3',5'-monophosphate and guanosine 3'.5'-monophosphate, in healthy adults treated with theophylline

    DEFF Research Database (Denmark)

    Fenger, M; Eriksen, P B; Andersen, O

    1982-01-01

    Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine monophosph......Plasma concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate were measured in 10 health adults before, during and after periods of theophylline administration. Cyclic adenosine monophosphate concentrations did not change significantly, but cyclic guanosine...... monophosphate concentrations decreased by 29% on average when theophylline was administered. The change in cyclic guanosine monophosphate was not correlated to the plasma concentration of theophylline in the range studied....

  13. High-dose inhaled corticosteroids or addition of theophylline in patients with poorly controlled asthma?

    Science.gov (United States)

    Celis, Pilar; Rada, Gabriel

    2015-08-19

    There are several management strategies for patients with poorly controlled asthma despite usual treatment. Increasing doses of inhaled corticosteroids or adding theophylline are among the therapeutic alternatives. However, the latter is associated with important adverse effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether theophylline or high-dose inhaled corticosteroids constitute a better alternative for symptomatic control or reduction in exacerbations in poorly controlled asthmatic patients because the certainty of the evidence is very low.

  14. Theophylline-associated status epilepticus in an infant: pharmacokinetics and the risk of suppository use.

    Science.gov (United States)

    Kato, Zenichiro; Yamagishi, Atsushi; Nakamura, Mitsuhiro; Kondo, Naomi

    2009-11-01

    Theophylline has been widely used to treat asthma, but recent studies have revealed that the possible risks for seizure may result in the revision of the therapeutic guidelines. An 8-month-old boy who had been treated with oral sustained-release theophylline and additional aminophylline suppository was hospitalized. A combination of diazepam, lidocaine and thiopental was required to stop his convulsion. The pharmacokinetic study indicated that the usage of a sustained-release formula should not usually be over 15 mg/ml, but the additional use of an aminophylline suppository elevated the concentration to over 20 mg/ml and resulted in the severe adverse effects. The parents of children and also physicians should be educated to ensure the proper use of the suppository formula.

  15. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    Science.gov (United States)

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Vibrational spectral investigation on xanthine and its derivatives—theophylline, caffeine and theobromine

    Science.gov (United States)

    Gunasekaran, S.; Sankari, G.; Ponnusamy, S.

    2005-01-01

    A normal coordinate analysis has been carried out on four compounds having a similar ring structure with different side chain substitutions, which are xanthine, caffeine, theophylline, and theobromine. Xanthine is chemically known as 2,6-dihydroxy purine. Caffeine, theophylline and theobromine are methylated xanthines. Considering the methyl groups as point mass, the number of normal modes of vibrations can be distributed as Γ vib=27 A'+12 A″ based on C s point group symmetry associated with the structures. In the present work 15 A' and 12 A″ normal modes are considered. A new set of orthonormal symmetry co-ordinates have been constructed. Wilson's F- G matrix method has been adopted for the normal coordinate analysis. A satisfactory vibrational band assignment has been made by employing the FTIR and FT Raman spectra of the compounds. The potential energy distribution is calculated with the arrived values of the force constants and hence the agreement of the frequency assignment has been checked.

  17. The influence of fatty acids on theophylline binding to human serum albumin. Comparative fluorescence study

    Science.gov (United States)

    Maciążek-Jurczyk, M.; Sułkowska, A.; Bojko, B.; Równicka-Zubik, J.; Szkudlarek-Haśnik, A.; Zubik-Skupień, I.; Góra, A.; Dubas, M.; Korzonek-Szlacheta, I.; Wielkoszyński, T.; Żurawiński, W.; Sosada, K.

    2012-04-01

    Theophylline, popular diuretic, is used to treat asthma and bronchospasm. In blood it forms complexes with albumin, which is also the main transporter of fatty acids. The aim of the present study was to describe the influence of fatty acids (FA) on binding of theophylline (Th) to human serum albumin (HSA) in the high affinity binding sites. Binding parameters have been obtained on the basis of the fluorescence analysis. The data obtained for the complex of Th and natural human serum albumin (nHSA) obtained from blood of obese patients qualified for surgical removal of stomach was compared with our previous studies on the influence of FA on the complex of Th and commercially available defatted human serum albumin (dHSA).

  18. Solid-state NMR studies of theophylline co-crystals with dicarboxylic acids.

    Science.gov (United States)

    Pindelska, Edyta; Sokal, Agnieszka; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Kolodziejski, Waclaw

    2014-11-01

    In this work, three polycrystalline materials containing co-crystals of theophylline with malonic, maleic, and glutaric acids were studied using (13)C, (15)N and (1)H solid-state NMR and FT-IR spectroscopy. The NMR assignments were supported by gauge including projector augmented waves (GIPAW) calculations of chemical shielding, performed using X-ray determined geometry. The experimental (13)C cross polarization/magic angle spinning (CP/MAS) NMR results and the calculated isotropic chemical shifts were in excellent agreement. A rapid and convenient method for theophylline co-crystals crystal structure analysis has been proposed for co-crystals, which are potentially new APIs. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Controlled release of theophylline from poly(vinyl alcohol) hydrogels/porous silicon nanostructured systems

    Science.gov (United States)

    Cervantes-Rincón, N.; Medellín-Rodríguez, F. J.; Escobar-Barrios, V. A.; Palestino, G.

    2013-03-01

    In this research, hybrid hydrogels of poly (vinyl alcohol)/ porous silicon (PSi)/theophylline were synthesized by the freezing and thawing method. We evaluated the influence of the synthesis parameters of the poly (vinyl alcohol) (PVA) hydrogels in relation to their ability to swell and drug released. The parameters studied (using an experimental design developed in Minitab 16) were the polymer concentration, the freezing temperature and the number of freezing/thawing (f/t) cycles. Nanostructured porous silicon particles (NsPSi) and theophylline were added within the polymer matrix to increase the drug charge and the polymer mechanical strength. The hybrid hydrogels were characterized by Infrared Spectroscopy Fourier Transform (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC), drug delivery kinetics were engineered according to the desired drug release schedule.

  20. Healthy live birth using theophylline in a case of retrograde ejaculation and absolute asthenozoospermia.

    Science.gov (United States)

    Ebner, Thomas; Shebl, Omar; Mayer, Richard Bernhard; Moser, Marianne; Costamoling, Walter; Oppelt, Peter

    2014-02-01

    To analyze whether the use of ready-to-use theophylline is a feasible option in a case of retrograde ejaculation and absolute asthenozoospermia. Case report. In vitro fertilization unit of a public hospital. Thirty-one-year-old nulliparous woman, and 39-year-old male with retrograde ejaculation and absolute asthenozoospermia. Retrieval of postejaculatory urine, restoration of motility using a methylxanthine, intracytoplasmic sperm injection, single-embryo transfer. Sperm motility, fertilization, embryo quality, live birth. Successful fertilization and a single-embryo transfer resulted in a healthy live birth. Theophylline turned out to be a safe, efficient agent for stimulating immotile spermatozoa in patients with retrograde ejaculation. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Pharmacolinetic and pharmacodynamic data analysis of theophylline for three different drug forms.

    Science.gov (United States)

    Richter, O; Reinhardt, D; Appel, R

    1981-11-01

    Theophylline, which is widely used in asthmatics, should be maintained within narrow plasma limits to achieve maximum therapeutic benefit with minimum adverse effects. For the evaluation of drug input schemes it is essential to know the pharmacokinetic parameters and their variation for different dosage forms. Apart from absorption and elimination rates, an appropriate dosage schedule is determined by the extent of bioavailability. The objectives of the study presented here are the assessment of bioavailability, the estimation of pharmacokinetic parameters, and the investigation of the relationship between plasma drug levels and cardiac side effects. Additionally, it was checked whether drug levels in saliva could be used for monitoring drug levels in plasma. The time course of theophylline in plasma and saliva was measured in twelve healthy volunteers on different drug forms: intravenous injection as well as oral application of a fast and a slow release form of theophylline. Pharmacokinetic parameters were estimated using a three-compartment model for the distribution of theophylline. The extent of bioavailability was estimated via the area under the curves and by numerical evaluation of the invasion function. By simultaneous measurements of heart rate and c-AMP levels the drug response was monitored. The results show the following: i) The slow and fast release dosage forms do not differ with respect to extent of bioavailability, whereas bioavailability rates are slower for the sustained release form. ii) Apart from the initial phase (less than or equal to 1 h) plasma and saliva drug levels run approximately parallel. However, the mean concentration ratio has a large variance. iii) The time courses of heart rate are closely related to the time courses of drug level. iv) When the sustained release form is used for a long-term therapy, it is possible to evaluate dosage schedules and dosage regimens that reduce cardiac side effects caused by the fast release form

  2. Spectral Analysis of Naturally Occurring Methylxanthines (Theophylline, Theobromine and Caffeine) Binding with DNA

    OpenAIRE

    Irudayam Maria Johnson; Halan Prakash; Jeyaguru Prathiba; Raghavachary Raghunathan; Raghunathan Malathi

    2012-01-01

    Nucleic acids exist in a dynamic equilibrium with a number of molecules that constantly interact with them and regulate the cellular activities. The inherent nature of the structure and conformational integrity of these macromolecules can lead to altered biological activity through proper targeting of nucleic acids binding ligands or drug molecules. We studied the interaction of naturally occurring methylxanthines such as theophylline, theobromine and caffeine with DNA, using UV absorption an...

  3. Modeling of drug release from multi-unit dosage tablets of theophylline

    African Journals Online (AJOL)

    A model of multi-unit dose tablets of theophylline (dose, 600 mg) has been designed to give a prompt release dose (200 mg) in the first 1 h and the remaining sustained release dose (400 mg) to be released over 11 h at a first order release rate constant of 0.24 h-1. The prompt release component (A) consisted of ...

  4. Influence of storage condition on properties of MCC II-based pellets with theophylline-monohydrate.

    Science.gov (United States)

    Krueger, Cornelia; Thommes, Markus; Kleinebudde, Peter

    2014-10-01

    Microcrystalline cellulose II (MCC II(1)) is a polymorph of commonly used MCC I; in 2010 it was introduced as new pelletization aid in wet-extrusion/spheronization leading to fast disintegrating pellets. Previous investigations suggested that the storage of the resulting pellets affect the disintegration behavior, the non-hygroscopic substance chloramphenicol that showed no polymorphism or hydrate formation due to relative humidity was used for the investigations. Therefore, theophylline-monohydrate that can dehydrate during storage, but also during manufacturing and drying was used for this study to confirm the results of the previous study and give a more detailed overview of the influence of recrystallization of theophylline monohydrate on disintegration. Storage recommendations should be derived. MCC II-based pellets were prepared of binary mixtures containing 10%, 20% or 50% MCCII as pelletization aid and theophylline-monohydrate as API. These pellets were stored at different relative humidity (0-97%rH; 20°C); the influence on their disintegration and drug release was investigated. The storage conditions had an impact on pellet disintegration. Low relative humidities (⩽ 40%rH) led to a conversion of the monohydrate to the anhydrous form. Newly grown crystals formed a kind of network around the pellet and inhibited the disintegration. High relative humidity (>80%rh) affected the disintegration caused by changes in the MCCII as already seen in the previous study. Due to the changed disintegration behavior also the drug release and release kinetic changed. Therefore, for theophylline containing pellets a storage humidity of 55%rH to 80%rH (20°C) is recommended. All in all, these investigations substantiate the knowledge of MCCII-based pellets providing a better basis for adequate storage conditions of MCCII based pellets. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Theophylline treatment improves mitochondrial function after upper cervical spinal cord hemisection

    Science.gov (United States)

    Hüttemann, Maik; Nantwi, Kwaku D.; Lee, Icksoo; Liu, Jenney; Mohiuddin, Syed; Petrov, Theodor

    2010-01-01

    The importance of mitochondria in spinal cord injury has mainly been attributed to their participation in apoptosis at the site of injury. But another aspect of mitochondrial function is the generation of more than 90% of cellular energy in the form of ATP, mediated by the oxidative phosphorylation (OxPhos) process. Cytochrome c oxidase (CcO) is a central OxPhos component and changes in its activity reflect changes in energy demand. A recent study suggests that respiratory muscle function in chronic obstructive pulmonary disease (COPD) patients is compromised via alterations in mitochondrial function. In an animal model of cervical spinal cord hemisection (C2HS) respiratory dysfunction, we have shown that theophylline improves respiratory function. In the present study, we tested the hypothesis that theophylline improves respiratory function at the cellular level via improved mitochondrial function in the C2HS model. We demonstrate that CcO activity was significantly (33%) increased in the spinal cord adjacent to the site of injury (C3–C5), and that administration of theophylline (20 mg/kg 3× daily orally) after C2HS leads to an even more pronounced increase in CcO activity of 62% compared to sham-operated animals. These results are paralleled by a significant increase in cellular ATP levels (51% in the hemidiaphragm ipsilateral to the hemisection). We conclude that C2HS increases energy demand and activates mitochondrial respiration, and that theophylline treatment improves energy levels through activation of the mitochondrial OxPhos process to provide energy for tissue repair and functional recovery after paralysis in the C2HS model. PMID:20144890

  6. Thermal and structural study on the lattice compound 1,4-diammoniumbutane bis(theophyllinate)

    Energy Technology Data Exchange (ETDEWEB)

    Ban, Margit; Madarasz, Janos; Bombicz, Petra; Pokol, Gyoergy; Gal, Sandor

    2004-10-01

    Crystalline title compound (1) prepared from aqueous solution of theophylline and 1,4-diaminobutane has been structurally and thermally characterized. Both the two-step TG decomposition curve and elemental analysis of the hexagonal crystals show that it consists of theophylline and 1,4-diaminobutane in 2:1 molar ratio. Actually, presence of one type of both theophyllinate anions and 1,4-diammoniumbutane dication have been indicated by FTIR spectroscopy. The molecular structure of lattice compound (1) has been determined by single crystal X-ray diffraction, where the hydrogen positions have been obtained from differential Fourier maps. It has confirmed that the crystal is really built up from these ionic constituents bound together with an extensive net of hydrogen bonds. The coupled TG-FTIR analysis of the evolved gases has revealed that the diamine is released as a whole molecule in the first decomposition step. Clathrate 1 and the proton migration in it might serve as a structural model of solid aminophylline whose crystal structure is still unknown.

  7. Effects of caffeine and its reactive metabolites theophylline and theobromine on the differentiating testis.

    Science.gov (United States)

    Pollard, I; Locquet, O; Solvar, A; Magre, S

    2001-01-01

    A previous study in the rat (Pollard et al. 1990) established that caffeine, when administered during pregnancy, significantly inhibited the differentiation of the seminiferous cords and subsequent Leydig cell development in the interstitium. However, that study could not distinguish between the direct effects of caffeine and/or the intermediary secondary toxic effects of metabolites such as theophylline and theobromine. Because the fetus lacks the appropriate enzyme systems, clearance of toxic substances takes place via the placenta and maternal liver. Thus, a suitable in vitro system can effectively differentiate between primary and secondary drug effects. In the present study, 13-day-old fetal testis, at the stage of incipient differentiation, were cultured for 4 days in vitro in the presence of graded doses of caffeine, theophylline or theobromine. It was found that explants exposed to caffeine or theobromine differentiated normally, developing seminiferous cords made up of Sertoli and germ cells, soon followed by the differentiation of functionally active Leydig cells appearing in the newly formed interstitium. However, explants exposed to theophylline failed to develop seminiferous cords and, as a consequence, Leydig cells. In conclusion, insights obtained from different experimental methods, such as organ culture or whole organism studies, are not always identical. It may be prudent, therefore, to take into account that certain experimental techniques, despite providing valuable information, may require confirmation by other test methods in order to obtain an in-depth understanding of mechanisms of action involved.

  8. Development of an RNA-based theophylline-specific microarray biosensor

    Science.gov (United States)

    Jordan, Katherine M.

    We are developing an extremely sensitive and compact biosensor that is adaptable to a variety of target analytes. Hammerhead ribozymes have been engineered such that they rearrange from a catalytically inactive to an active conformation upon binding to a target molecule. A donor-acceptor fluorophore pair is coupled to the substrate RNA of such an aptamer, to form a complex referred to as an aptazyme, to monitor real-time cleavage activity in a fluid environment. The fluorophores interact by fluorescence resonance energy transfer (FRET) until binding of the target molecule, when the FRET signal breaks down as the substrate is cleaved and the products dissociate. FRET assays with immobilized aptazymes and using total internal reflection fluorescence (TIRF) microscopy on the single-molecule scale are presented showing an enhancement of substrate cleavage in the presence of theophylline over background. The aptazyme is hybridized onto a DNA microarray and incorporated into a chip specifically designed to allow for measurement in a controlled fluid environment. The use of these microarrays allows for either one spot, or a series of spots, to be addressed independently within the biosensor. This allows for multiple analytes to be tested simultaneously. An enhancement in the substrate cleavage is again observed in the presence of theophylline. Results are presented toward the characterization of a theophylline-specific aptamer-based biosensor using this RNA microarray platform and analogous measurement techniques.

  9. Polymorphs of Theophylline Characterized by DNP Enhanced Solid-State NMR.

    Science.gov (United States)

    Pinon, Arthur C; Rossini, Aaron J; Widdifield, Cory M; Gajan, David; Emsley, Lyndon

    2015-11-02

    We show how dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy can be used to characterize polymorphs and solvates of organic solids. We applied DNP to three polymorphs and one hydrated form of the asthma drug molecule theophylline. For some forms of theophylline, sample grinding and impregnation with the radical-containing solution, which are necessary to prepare the samples for DNP, were found to induce polymorphic transitions or desolvation between some forms. We present protocols for sample preparation for solid-state magic-angle spinning (MAS) DNP experiments that avoid the polymorphic phase transitions in theophylline. These protocols include cryogrinding, grinding under inert atmosphere, and the appropriate choice of the impregnating liquid. By applying these procedures, we subsequently demonstrate that two-dimensional correlation experiments, such as (1)H-(13)C and (1)H-(15)N HETCOR or (13)C-(13)C INADEQUATE, can be obtained at natural isotopic abundance in reasonable times, thus enabling more advanced structural characterization of polymorphs.

  10. In vitro release profiles of PLGA core-shell composite particles loaded with theophylline and budesonide.

    Science.gov (United States)

    Yeh, Hsi-Wei; Chen, Da-Ren

    2017-08-07

    We investigated the effects of drug loading location, matrix material and shell thickness on the in vitro release of combinational drugs from core-shell PLGA (i.e., poly(lactic-co-glycolic acid)) particles. Budesonide and Theophylline were selected as highly hydrophobic and hydrophilic model drugs, respectively. The dual-capillary electrospray (ES) technique, operated at the cone-jet mode, was used to produce samples of drug-loaded core-shell composite particles with selected overall sizes, polymer materials, and shell thicknesses. Theophylline and Budesonide were loaded at different locations in a PLGA composite particle. This study illustrated how the aforementioned factors affect the release rates of Budesonide and Theophylline loaded in core-shell PLGA composites. We further identified that core-shell composite particles with both model drugs loaded in the core and with matrix PLGA polymers of low molecular weights and low LA/GA ratios are the best formulation for the sustained release of highly hydrophilic and hydrophobic active pharmaceutical ingredients from PLGA composite particles. The formulation strategy obtained in this study can be in principle generalized for biopharmaceutical applications in fixed-dose combination therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Effect of potassium chloride on diffusion of theophylline at T = 298.15 K

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Cecilia I.A.V., E-mail: cecilia.alves@uah.e [Departamento de Quimica Fisica, Facultad de Farmacia, Universidad de Alcala, 28871 Alcala de Henares, Madrid (Spain); Lobo, Victor M.M., E-mail: vlobo@ci.uc.p [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Esteso, Miguel A., E-mail: miguel.esteso@uah.e [Departamento de Quimica Fisica, Facultad de Farmacia, Universidad de Alcala, 28871 Alcala de Henares, Madrid (Spain); Ribeiro, Ana C.F., E-mail: anacfrib@ci.uc.p [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal)

    2011-06-15

    Research highlights: {yields} Mutual diffusion coefficients of theophylline in aqueous dilute solutions. {yields} Influence of the presence of potassium chloride in the aqueous media. {yields} Estimation of the association constant, K, between THP and KCl. - Abstract: Ternary mutual diffusion coefficients measured by Taylor dispersion method (D{sub 11}, D{sub 22}, D{sub 12}, and D{sub 21}) are reported for aqueous solutions of KCl + theophylline (THP) at T = 298.15 K at carrier concentrations from (0.000 to 0.010) mol {center_dot} dm{sup -3}, for each solute. These diffusion coefficients have been measured having in mind a better understanding of the structure of these systems and the thermodynamic behavior of potassium chloride and theophylline in solution. For example, from these data it will be possible to make conclusions about the influence of this electrolyte in diffusion of THP and to estimate some parameters, such as the diffusion coefficient of the aggregate between KCl and THP.

  12. Positive benefits of theophylline in a randomized, double-blind, parallel-group, placebo-controlled study of low-dose, slow-release theophylline in the treatment of COPD for 1 year.

    Science.gov (United States)

    Zhou, Yumin; Wang, Xiaoping; Zeng, Xiangyi; Qiu, Rong; Xie, Junfeng; Liu, Shengming; Zheng, Jingping; Zhong, Nanshan; Ran, Pixin

    2006-09-01

    Increasing evidence suggests that low-dose theophylline has anti-inflammatory benefits and is safe in the treatment of COPD. This study aims to evaluate the efficacy and safety of low-dose, slow-release oral theophylline administered over a 1-year period in patients with COPD. A randomized, double-blind, parallel-group, placebo-controlled trial was carried out. In total, 110 participants with COPD were randomly assigned to receive slow-release theophylline (100 mg b.i.d.) or placebo for 1 year. Use of medicine and symptoms recorded by diary cards; pulmonary function, exacerbations of COPD, quality of life and the use of rescue medicine were evaluated. Superiority test was used to estimate the efficacy. Of 110 participants, 85 (77.3%) complied with the protocol, with 42 subjects in theophylline and 43 subjects on placebo. In both intention-to-treat and per-protocol population analysis, greater improvement in pre-bronchodilator FEV(1) (P = 0.038 and P = 0.070, respectively), lower frequency of COPD exacerbations (P = 0.047 and P = 0.035, respectively), fewer days of COPD exacerbations (P = 0.045 and P = 0.046, respectively), lower frequency of clinical visits (P = 0.017 and P = 0.039, respectively), greater improvement in satisfaction with treatment (P = 0.014 and P = 0.004, respectively) were found in the theophylline group than in the placebo group. In per-protocol population, greater improvements in quality of life (P = 0.047) were also observed in the theophylline group and the mean time to the first exacerbation was delayed in theophylline group in comparison with placebo group (P = 0.047). Drug-related adverse events such as stomach discomfort (3.51%), headache (3.51%), insomnia (1.75%) and palpitation (1.75%) were found in the theophylline group. Low-dose, slow-release oral theophylline is effective and well-tolerated in the long term treatment of stable COPD, although it does not improve post-bronchodilator lung function.

  13. [Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease].

    Science.gov (United States)

    Wang, Chang-Hui; Zhang, Qian; Li, Ming; Fu, Pei-Fang; Yan, Zheng-Mao; Peng, Ai-Mei; Zhang, Guo-Liang

    2010-03-02

    To evaluate the efficacy and safety of oral theophylline versus placebo in patients with stable chronic obstructive pulmonary disease (COPD). The databases Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Chinese Biomedical Database were retrieved by using the key words "Uniphyl or Theophylline or Theo-Dur or theo or Theotrim or Elixophyllin or Elixophyllin or Phyllocontin or aminophylline or Methylxanthine or nuelin or doxofylline" and "obstructive or bronchitis or pulmonary emphysema or bronchial hyperreactivity or COPD or COLD or emphysema" so as to search the materials about the randomized controlled clinical trials comparing the effectiveness of stable COPD treated by oral theophylline and placebo. A meta-analysis was conducted. For continuous variables, the results of individual studies were pooled using fixed-effect weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). Where the results were expressed as dichotomous variables, the relative risk (RR) with 95%CI was calculated. Thirty-four documents about randomized controlled clinical trials, including a total of 2087 patients, from the retrieved 2010 documents accorded to the demand of enrollment. The results of meta-analysis showed that theophylline significantly improved the forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate (WMD 0.09 L, 95%CI 0.09 - 0.09; WMD 0.14 L, 95%CI 0.13 - 0.14; WMD 17.0 L/min and 95%CI 6.9 - 27.2 respectively). Arterial oxygen tension and arterial carbon dioxide tension at rest both improved with treatment (WMD 2.89 mm Hg, 95%CI 1.11 - 4.66; WMD -2.05 mm Hg and 95%CI -3.59 to -1.42 respectively). Six-minute walk distance significantly improved (WMD 38.89 meters, 95%CI 21.55 - 56.22) in treatment group. The RR of acute exacerbations was smaller between both groups (RR 0.74, 95%CI 0.59 - 0.93). The RR of total adverse events was similar (RR 1.05, 95%CI 0.95 - 1.16) while RR of drug

  14. Hydroxyl radical induced oxidation of theophylline in water: a kinetic and mechanistic study.

    Science.gov (United States)

    Sunil Paul, M M; Aravind, U K; Pramod, G; Saha, A; Aravindakumar, C T

    2014-08-14

    Oxidative destruction and mineralization of emerging organic pollutants by hydroxyl radicals (˙OH) is a well established area of research. The possibility of generating hazardous by-products in the case of ˙OH reaction demands extensive investigations on the degradation mechanism. A combination of pulse radiolysis and steady state photolysis (H2O2/UV photolysis) followed by high resolution mass spectrometric (HRMS) analysis have been employed to explicate the kinetic and mechanistic features of the destruction of theophylline, a model pharmaceutical compound and an identified pollutant, by ˙OH in the present study. The oxidative destruction of this molecule, for intermediate product studies, was initially achieved by H2O2/UV photolysis. The transient absorption spectrum corresponding to the reaction of ˙OH with theophylline at pH 6, primarily caused by the generation of (T8-OH)˙, was characterised by an absorption band at 330 nm (k2 = (8.22 ± 0.03) × 10(9) dm(3) mol(-1) s(-1)). A significantly different spectrum (λmax: 340 nm) was observed at highly alkaline pH (10.2) due to the deprotonation of this radical (pKa∼ 10.0). Specific one electron oxidants such as sulphate radical anions (SO4˙(-)) and azide radicals (N3˙) produce the deprotonated form (T(-H)˙) of the radical cation (T˙(+)) of theophylline (pKa 3.1) with k2 values of (7.51 ± 0.04) × 10(9) dm(3) mol(-1) s(-1) and (7.61 ± 0.02) × 10(9) dm(3) mol(-1) s(-1) respectively. Conversely, oxide radicals (O˙(-)) react with theophylline via a hydrogen abstraction protocol with a rather slow k2 value of (1.95 ± 0.02) × 10(9) dm(3) mol(-1) s(-1). The transient spectral studies were complemented by the end product profile acquired by HRMS analysis. Various transformation products of theophylline induced by ˙OH were identified by this technique which include derivatives of uric acids (i, iv & v) and xanthines (ii, iii & vi). Further breakdown of the early formed product due to ˙OH attack leads to

  15. A novel electrochemical method to detect theophylline utilizing silver ions captured within abasic site-incorporated duplex DNA.

    Science.gov (United States)

    Ahn, Jun Ki; Park, Ki Soo; Won, Byoung Yeon; Park, Hyun Gyu

    2015-05-15

    We herein describe a novel and label-free electrochemical system to detect theophylline. The system was constructed by immobilizing duplex DNA containing an abasic site opposite cytosine on the gold electrode surface. In the absence of theophylline in a sample, silver ions freely bind to the empty abasic site in the duplex DNA leading to the highly elevated electrochemical signal by the redox reaction of silver ions. On the other hand, when theophylline is present, it binds to the abasic site by pseudo base pairing with the opposite cytosine nucleobase, which consequently prevents silver ions from binding to the abasic site. As a result, redox reaction of silver ions would be greatly reduced resulting in the accordingly decreased electrochemical signal. By employing this electrochemical strategy, theophylline was reliably detected at a concentration as low as 3.2 μM with the high selectivity over structurally similar substances such as caffeine and theobromine. Finally, the diagnostic capability of this method was also successfully verified by reliably detecting theophylline present in a real human serum sample with an excellent recovery ratio within 100±6%. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Induction of hepatic cytochrome P450s by the herbal medicine Sophora flavescens extract in rats: impact on the elimination of theophylline.

    Science.gov (United States)

    Ueng, Yune-Fang; Tsai, Ching-Chin; Lo, Wei-Sheng; Yun, Chul-Ho

    2010-01-01

    The roots of Sophora flavescens (Sf) have been widely used as a herbal medicine for the treatment of diarrhea, gastrointestinal hemorrhage, and eczema. Cytochrome P450 (P450) forms including CYP1A2, CYP2B, CYP2E1, and CYP3A participate in the oxidative metabolism of theophylline, which is an important bronchodilation agent with a narrow therapeutic index. To assess the interaction of Sf with theophylline, the effects of Sf extract on theophylline-metabolizing P450s and on the pharmacokinetic profile of theophylline were investigated in male Sprague-Dawley rats. Oral treatment of rats with the Sf extract caused dose-dependent increases of liver microsomal oxidation activities toward 7-ethoxyresorufin, 7-pentoxyresorufin, and nifedipine. However, nitrosodimethylamine N-demethylation activity was not affected. The ingestion of Sf extract stimulated theophylline 8-oxidation and N-demethylation activities. The increases of oxidative activities were in consensus with the elevation of the protein levels of CYP1A2, CYP2B1/2, CYP2C11, and CYP3A. Sf-treatment increased the clearance of theophylline and decreased the area under the concentration-time curve (AUC) and the area under the moment curve (AUMC). These results demonstrate that Sf reduces blood theophylline concentration through facilitating the elimination of theophylline. In patients taking Sf, possible P450 induction-induced drug interaction should be noted to decrease the risk of therapeutic failure or adverse effects resulting from the use of additional therapeutic agents.

  17. In vitro studies of theophylline-induced changes in Na, K and Cl transport in hen (Gallus domesticus) colon suggesting bidirectional, basolateral NaK2Cl cotransport

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Munck, B G; Munck, L K

    1990-01-01

    1. In isolated mucosa from a NaCl-loaded hen theophylline stimulates both unidirectional chloride fluxes (JmsCl and JsmCl). Conductive and electroneutral exchange processes, besides a bumetanide-sensitive, rheogenic process contribute. 2. The bumetanide-sensitive fraction of the theophylline...

  18. Target-controlled formation of silver nanoclusters in abasic site-incorporated duplex DNA for label-free fluorescence detection of theophylline

    Science.gov (United States)

    Park, Ki Soo; Oh, Seung Soo; Soh, H. Tom; Park, Hyun Gyu

    2014-08-01

    A novel, label-free, fluorescence based sensor for theophylline has been developed. In the new sensor system, an abasic site-incorporated duplex DNA probe serves as both a pocket for recognition of theophylline and a template for the preparation of fluorescent silver nanoclusters. The strategy relies on theophylline-controlled formation of fluorescent silver nanoclusters from abasic site-incorporated duplex DNA. When theophylline is not present, silver ions interact with the cytosine groups opposite to the abasic site in duplex DNA. This interaction leads to efficient formation of intensely red fluorescent silver nanoclusters. In contrast, when theophylline is bound at the abasic site through pseudo base-pairing with appropriately positioned cytosines, silver ion binding to the cytosine nucleobase is prevented. Consequently, fluorescent silver nanoclusters are not formed causing a significant reduction of the fluorescence signal. By employing this new sensor, theophylline can be highly selectively detected at a concentration as low as 1.8 μM. Finally, the diagnostic capability and practical application of this sensor were demonstrated by its use in detecting theophylline in human blood serum.A novel, label-free, fluorescence based sensor for theophylline has been developed. In the new sensor system, an abasic site-incorporated duplex DNA probe serves as both a pocket for recognition of theophylline and a template for the preparation of fluorescent silver nanoclusters. The strategy relies on theophylline-controlled formation of fluorescent silver nanoclusters from abasic site-incorporated duplex DNA. When theophylline is not present, silver ions interact with the cytosine groups opposite to the abasic site in duplex DNA. This interaction leads to efficient formation of intensely red fluorescent silver nanoclusters. In contrast, when theophylline is bound at the abasic site through pseudo base-pairing with appropriately positioned cytosines, silver ion binding to

  19. Impact of an oral theophylline loading dose pre-electroconvulsive therapy: a retrospective study in patients with missed or inadequate seizures.

    Science.gov (United States)

    Kemp, Michael F; Allard, Jacques; Pâquet, Myriam; Marcotte, Patrick

    2015-03-01

    The aim of this study was to determine the safety and impact of an oral theophylline loading dose calculated to achieve a 10- to 15-mg/L plasma concentration when administered 1.5 hours before electroconvulsive therapy (ECT). We conducted a retrospective study using inpatient hospital records between January 2007 and June 2012 at the Dr. Georges L. Dumont University Hospital Centre. Patients receiving a series of ECTs with a calculated theophylline loading dose were selected. Variables collected include ECT parameters for each ECT, medications received, and treatment-related side effects. We identified 35 patients and analyzed 14 who had no treatment modifications except for the addition of theophylline. The mean predicted theophylline plasma concentration was 12.99 (SD, 1.09) mg/L with dosages ranging from 260 to 600 mg. Eight patients (89%) with abortive seizures and 4 (80%) with missed seizures achieved a seizure duration of greater than 15 seconds with theophylline. Seizure duration increased by 165.6% (+21.3 seconds; P = 0.048) with theophylline, and all patients (N = 5) with a maximum sustained coherence of less than 92% achieved an increase after theophylline; however, the overall increase (+8.8%, P = 0.087) was not significant. No theophylline-related adverse events were documented in 128 ECTs with theophylline, and no seizure exceeded 120 seconds. A calculated theophylline loading dose before ECT is well tolerated and effective in prolonging seizure duration and aiding with seizure generation in patients who do not seize readily. Its positive impact in patients with lower maximum sustained coherence, in addition to the potential existence of a dose-response relationship, should be further investigated.

  20. [Theophylline in the treatment of chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study].

    Science.gov (United States)

    Zhou, Yu-min; Wang, Xiao-ping; Zeng, Xiang-yi; Qiu, Rong; Xie, Jun-fen; Liu, Sheng-ming; Zheng, Jin-ping; Zhong, Nan-shan; Ran, Pi-xin

    2006-09-01

    To observe the benefits and safety of low-dose, slow-release oral theophylline for long-term treatment of stable chronic obstructive pulmonary disease (COPD). This was a randomized, parallel-group, double-blind, placebo-controlled trial. Slow-release theophylline (200 mg/d) twice daily or placebo (matching theophylline) was randomly given to 110 patients with stable COPD in the rural area of Shaoguan, Guangdong Province, for one year. Efficacy measures were spirometry and exacerbations, quality of life, dyspnea scores, satisfaction with treatments and adverse effects. Comparison of benefits was performed using superiority test. Of 110 patients, 85 (42 subjects in theophylline group and 43 subjects in placebo group) completed the study. An analysis for intention-to-treat (ITT) individuals showed that individuals with the treatment of theophylline experienced statistically fewer numbers [(0.8 +/- 1.2) times/year, (1.7 +/- 2.6) times/year, Z = -1.674, P = 0.047] and days of exacerbations [(4.6 +/- 7.9) d, (12.5 +/- 22.8) d, Z = -1.699, P = 0.045] in comparison to subjects receiving placebo, that patients receiving theophylline were less likely than the placebo group to experience moderate exacerbations [(0.4 +/- 1.0) times/year, (1.0 +/- 1.8) times/year, Z = -2.136, P = 0.017], and that more individuals satisfied with treatments in the theophylline group than the placebo group (n = 16, 3, Z = -2.198, P = 0.014), and that statistically greater improvement in pre-bronchodilators FEV(1) [(0.006 +/- 0.180) L, (-0.053 +/- 0.169) L, t = 1.789, P = 0.038] were found in the theophylline group in comparison to the placebo group. The similar results were observed in an analysis for per-protocol (PP) subjects. Statistical improvement on quality of life was observed in the PP subjects of theophylline group than in placebo group (-28 +/- 20, -20 +/- 23, F = 2.893, P = 0.047). Time to the first exacerbation in patients receiving theophylline was also delayed in comparison to

  1. Enhanced elimination of theophylline, phenobarbital and strychnine from the bodies of rats and mice by squalane treatment.

    Science.gov (United States)

    Kamimura, H; Koga, N; Oguri, K; Yoshimura, H

    1992-05-01

    Our previous study suggested that squalane would be a good candidate for an antidote to reduce the toxicity of drug ingested accidentally at a high dose by enhancing the drug elimination from the body. In the present study, we investigated whether squalane given orally could enhance the elimination of theophylline, phenobarbital and strychnine which were administered parenterally to rats or mice. Squalane increased the fecal excretion of theophylline and reduced the serum level of the drug in rats. Squalane accelerated the fecal excretion of strychnine in mice. These results suggest that squalane may stimulate more the elimination of neutral (theophylline) or basic (strychnine) drugs which should be present in unionized form in intestinal lumen, than that of acidic drugs.

  2. Demonstrating the effect of theophylline treatment on diaphragmatic movement in chronic obstructive pulmonary disease patients by MR-fluoroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Etlik, Omer E-mail: omeretlik@hotmail.com; Sakarya, M. Emin; Uzun, Kursat; Harman, Mustafa; Temizoz, Osman; Durmus, Ahmet

    2004-08-01

    Introduction: The purpose of this study was to determine the increase in diaphragmatic excursion of patients with chronic obstructive pulmonary disease (COPD) treated with theophylline by MR-fluoroscopy which is an innovative method to demonstrate effectiveness of this treatment. Materials and methods: Investigations were performed on a 0.3 T open MR unit. MR-fluoroscopy images of 30 patients with COPD were obtained before and after theophylline treatment. Diaphragmatic movement values were recorded for evaluation. Results: The response of the diaphragmatic movement in COPD patients treated with theophylline was evaluated by MR-fluoroscopy and an increase of 48% in diaphragmatic contractility was determined after the treatment. The increase in contractility was found to be parallel with respiratory function tests and clinical status. Conclusion: Diaphragmatic movement and response to the medical therapy in patients with COPD can be evaluated by MR-fluoroscopy method which can allow accurate measurements.

  3. Role of excipients in hydrate formation kinetics of theophylline in wet masses studied by near-infrared spectroscopy

    DEFF Research Database (Denmark)

    Jørgensen, Anna C; Airaksinen, Sari; Karjalainen, Milja

    2004-01-01

    . Anhydrous theophylline was chosen as the hydrate-forming model drug compound and two excipients, silicified microcrystalline cellulose (SMCC) and alpha-lactose monohydrate, with different water absorbing properties, were used in formulation. An early stage of wet massing was studied with anhydrous...... theophylline and its 1:1 (w/w) mixtures with alpha-lactose monohydrate and SMCC with 0.1g/g of purified water. The changes in the state of water were monitored using near-infrared spectroscopy, and the conversion of the crystal structure was verified using X-ray powder diffraction (XRPD). SMCC decreased...... the hydrate formation rate by absorbing water, but did not inhibit it. The results suggest that alpha-lactose monohydrate slightly increased the hydrate formation rate in comparison with a mass comprising only anhydrous theophylline....

  4. The Study of Efficacy, Tolerability and Safety of Theophylline Given Along with Formoterol Plus Budesonide in COPD.

    Science.gov (United States)

    Subramanian; Ragulan; Jindal, Apar; Viswambhar, V; V, Arun Babu

    2015-02-01

    Chronic obstructive pulmonary disease (COPD) is a common disease causing significant socioeconomic burden. COPD patients, commonly smokers develop resistance to inhaled steroids attributed to deficiency of histone deacetylase 2 (HDAC2). The study of relationship between systemic inflammation and functional performance demonstrated that increased CRP level is inversely related to six minute walk distance (SMWD) and Forced Expired Volume in one second (FEV1). Theophylline restores HDAC2 activity thereby unlocking steroid resistance and potentiating inhaled corticosteroids (ICS) action culminating in reduced airway inflammation and mortality. To study the effects of addition of Theophylline to the combination of Formoterol plus Budesonide on various objective and subjective parameters in moderate to severe COPD patients and to assess the safety profile of the combination. Setting and Study design: A single blinded, prospective, randomized, placebo controlled study at a tertiary care hospital in Jaipur, India. Fifty eight patients diagnosed with moderate to severe COPD were randomized into two groups. Group A patients received Formoterol 24μg plus budesonide 800μg daily in divided doses along with Theophylline while group B patients received Formoterol 24μg plus budesonide 800μg daily in divided doses along with placebo tablets. Both groups were followed up on 15th, 30th &60th day. During every visit all patients were assessed subjectively (symptom scoring) and objectively (spirometry, CRP, SMWT) and adverse effects if any were recorded. The obtained data subject to statistical analysis using"Graph pad Instat3" software. Statistically significant improvement with a decline in total symptom score (p Theophylline group showed significant improvement in SMWD and FEV1.Mean fall in CRP was greater in Group A (not statistically significant). No side effects requiring withdrawal of drug were noted with Theophylline. Addition of Theophylline to Formoterol plus Budesonide

  5. Theophylline, an old drug with multi-faceted effects: Its potential benefits in immunological liver injury in rats.

    Science.gov (United States)

    Hussein, Reeham Mohamed; Elsirafy, Osama Mahmod; Wahba, Yousria Saad; Kawy, Hala Salah Abdel; Hasanin, Amany Helmy; Hamam, Ghada Galal

    2015-09-01

    A low dose of theophylline enhances histone deacetylase activity leading to inhibition of proinflammatory transcription, and inhibits lung fibroblast proliferation. The present work investigated the effect of lowdose theophylline on biochemical and histological pictures of liver tissues in rats with immunological hepatic injury induced by concanavalin A (Con A). Ratswere assigned to control vehicle,model (Con A) and theophylline groups. Half of the animals in each group were sacrificed at the end of the 4th week and the other half were sacrificed at the end of the 8th week. There was a time-dependent increase in the liver injury parameters by the end of the 4th and 8th weeks in the Con A treated group. Theophylline (20 mg/kg/day), produced a significant decrease in serum liver enzymes (ALT, AST), serum interferon gamma (IFN-γ) levels and the hepatic transforming growth factor-β (TGF-β) level. A significant decrease in liver tissue hydroxyproline content together with reduction in portal hypertension at the end of the 8th week was detected compared to the Con A group. Theophylline treated rats exhibited a significant decrease in hepatic vacuolation, apoptosis, leucocyte infiltration, and accumulation of collagen fibers in comparison to the Con A group. In addition, significant decreases in the area percentage of fibrosis and the area percentage of caspase +ve cells were reported compared to the Con A group. Theophylline effectively reduced the inflammation of liver tissues and alleviated the liver damage by decreasing IFN-γ and TGF-β in liver tissues of rats with immunological hepatic injury.

  6. Quantitative capillary electrophoresis and its application in analysis of alkaloids in tea, coffee, coca cola, and theophylline tablets.

    Science.gov (United States)

    Li, Mengjia; Zhou, Junyi; Gu, Xue; Wang, Yan; Huang, Xiaojing; Yan, Chao

    2009-01-01

    A quantitative CE (qCE) system with high precision has been developed, in which a 4-port nano-valve was isolated from the electric field and served as sample injector. The accurate amount of sample was introduced into the CE system with high reproducibility. Based on this system, consecutive injections and separations were performed without voltage interruption. Reproducibilities in terms of RSD lower than 0.8% for retention time and 1.7% for peak area were achieved. The effectiveness of the system was demonstrated by the quantitative analysis of caffeine, theobromine, and theophylline in real samples, such as tea leaf, roasted coffee, coca cola, and theophylline tablets.

  7. Spectral analysis of naturally occurring methylxanthines (theophylline, theobromine and caffeine) binding with DNA.

    Science.gov (United States)

    Johnson, Irudayam Maria; Prakash, Halan; Prathiba, Jeyaguru; Raghunathan, Raghavachary; Malathi, Raghunathan

    2012-01-01

    Nucleic acids exist in a dynamic equilibrium with a number of molecules that constantly interact with them and regulate the cellular activities. The inherent nature of the structure and conformational integrity of these macromolecules can lead to altered biological activity through proper targeting of nucleic acids binding ligands or drug molecules. We studied the interaction of naturally occurring methylxanthines such as theophylline, theobromine and caffeine with DNA, using UV absorption and Fourier transform infrared (FTIR) spectroscopic methods, and especially monitored their binding affinity in the presence of Mg(2+) and during helix-coil transitions of DNA by temperature (T(m)) or pH melting profiles. The study indicates that all these molecules effectively bind to DNA in a dose dependent manner. The overall binding constants of DNA-theophylline = 3.5×10(3) M(-1), DNA-theobromine = 1.1×10(3) M(-1), and DNA-Caffeine = 3.8×10(3) M(-1). On the other hand T(m)/pH melting profiles showed 24-35% of enhanced binding activity of methylxanthines during helix-coil transitions of DNA rather than to its native double helical structure. The FTIR analysis divulged that theophylline, theobromine and caffeine interact with all the base pairs of DNA (A-T; G-C) and phosphate group through hydrogen bond (H-bond) interaction. In the presence of Mg(2+), methylxanthines altered the structure of DNA from B to A-family. However, the B-family structure of DNA remained unaltered in DNA-methylxanthines complexes or in the absence of Mg(2+). The spectral analyses indicated the order of binding affinity as "caffeine≥theophylline>theobromine" to the native double helical DNA, and "theophylline≥theobromine>caffeine to the denatured form of DNA and in the presence of divalent metal ions.

  8. Spectral analysis of naturally occurring methylxanthines (theophylline, theobromine and caffeine binding with DNA.

    Directory of Open Access Journals (Sweden)

    Irudayam Maria Johnson

    Full Text Available Nucleic acids exist in a dynamic equilibrium with a number of molecules that constantly interact with them and regulate the cellular activities. The inherent nature of the structure and conformational integrity of these macromolecules can lead to altered biological activity through proper targeting of nucleic acids binding ligands or drug molecules. We studied the interaction of naturally occurring methylxanthines such as theophylline, theobromine and caffeine with DNA, using UV absorption and Fourier transform infrared (FTIR spectroscopic methods, and especially monitored their binding affinity in the presence of Mg(2+ and during helix-coil transitions of DNA by temperature (T(m or pH melting profiles. The study indicates that all these molecules effectively bind to DNA in a dose dependent manner. The overall binding constants of DNA-theophylline = 3.5×10(3 M(-1, DNA-theobromine = 1.1×10(3 M(-1, and DNA-Caffeine = 3.8×10(3 M(-1. On the other hand T(m/pH melting profiles showed 24-35% of enhanced binding activity of methylxanthines during helix-coil transitions of DNA rather than to its native double helical structure. The FTIR analysis divulged that theophylline, theobromine and caffeine interact with all the base pairs of DNA (A-T; G-C and phosphate group through hydrogen bond (H-bond interaction. In the presence of Mg(2+, methylxanthines altered the structure of DNA from B to A-family. However, the B-family structure of DNA remained unaltered in DNA-methylxanthines complexes or in the absence of Mg(2+. The spectral analyses indicated the order of binding affinity as "caffeine≥theophylline>theobromine" to the native double helical DNA, and "theophylline≥theobromine>caffeine to the denatured form of DNA and in the presence of divalent metal ions.

  9. Prophylactic Effect of Theophylline in Renal Contrast Nephropathy after Coronary Angiography

    Directory of Open Access Journals (Sweden)

    Asadollah Mohseni

    2006-07-01

    Full Text Available Background: Contrast nephropathy will increase mortality up to 30% following angiographic procedures. Adenosine is a crucial mediator of contrast-induced nephropathy. The purpose of this study was to investigate whether the adenosine antagonist Theophylline reduces the incidence of CN after coronary angiography.Methods: In this randomized, double-blind, placebo-controlled clinical trial study, carried out from February 2004 to September 2005 at the Fatemeh Zahra Hospital, 70 patients who were undergoing coronary angiography were divided into two groups. Case group (n=35 received oral Theophylline 200 mg bid. 24 h before and for 48 h after angiography. The control group (n=35 received placebo. Serum Na+, K+, blood urea nitrogen (BUN, creatinine, glomerular filtration rate (GFR were measured before and after angiography.Results: In the case group there were no significant change in serum creatinine (0.90± 0.7 vs. 0.92±0.3 mg/dl, BUN (17.76±7.8 vs. 19.35±9.6 mg/dl, GFR (83.01±26.7 vs. 81.36±24.9 ml/min Na+ (139.08±3.6 vs. 138.54±2.7 mEq/l and K+ (4.30±0.4 vs. 4.19±0.3 mEq/l. In the control group, there was a significant fall in GFR after angiography (86.10±34.8 vs. 80.7±30.4 ml/min, P=0.03. Following angiography, there were no significant difference in serum creatinine, BUN, GFR, Na+ and K+ level between the two groups. None of the patients in either group faced contrast induced nephropathy. Conclusion: Theophylline does not appear to add a protective role in preventing against contrast induced nephropathy in patients undergoing angiographic procedures.

  10. Spectral Analysis of Naturally Occurring Methylxanthines (Theophylline, Theobromine and Caffeine) Binding with DNA

    Science.gov (United States)

    Johnson, Irudayam Maria; Prakash, Halan; Prathiba, Jeyaguru; Raghunathan, Raghavachary; Malathi, Raghunathan

    2012-01-01

    Nucleic acids exist in a dynamic equilibrium with a number of molecules that constantly interact with them and regulate the cellular activities. The inherent nature of the structure and conformational integrity of these macromolecules can lead to altered biological activity through proper targeting of nucleic acids binding ligands or drug molecules. We studied the interaction of naturally occurring methylxanthines such as theophylline, theobromine and caffeine with DNA, using UV absorption and Fourier transform infrared (FTIR) spectroscopic methods, and especially monitored their binding affinity in the presence of Mg2+ and during helix-coil transitions of DNA by temperature (Tm) or pH melting profiles. The study indicates that all these molecules effectively bind to DNA in a dose dependent manner. The overall binding constants of DNA-theophylline = 3.5×103 M−1, DNA-theobromine = 1.1×103 M−1, and DNA-Caffeine = 3.8×103 M−1. On the other hand Tm/pH melting profiles showed 24–35% of enhanced binding activity of methylxanthines during helix-coil transitions of DNA rather than to its native double helical structure. The FTIR analysis divulged that theophylline, theobromine and caffeine interact with all the base pairs of DNA (A-T; G-C) and phosphate group through hydrogen bond (H-bond) interaction. In the presence of Mg2+, methylxanthines altered the structure of DNA from B to A-family. However, the B-family structure of DNA remained unaltered in DNA-methylxanthines complexes or in the absence of Mg2+. The spectral analyses indicated the order of binding affinity as “caffeine≥theophylline>theobromine” to the native double helical DNA, and “theophylline≥theobromine>caffeine to the denatured form of DNA and in the presence of divalent metal ions. PMID:23236361

  11. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

    Science.gov (United States)

    Stavrakov, Georgi; Valcheva, Violeta; Voynikov, Yulian; Philipova, Irena; Atanasova, Mariyana; Konstantinov, Spiro; Peikov, Plamen; Doytchinova, Irini

    2016-03-01

    The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non-toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. © 2015 John Wiley & Sons A/S.

  12. The Evidence for Intravenous Theophylline Levels between 10-20mg/L in Children Suffering an Acute Exacerbation of Asthma: A Systematic Review.

    Science.gov (United States)

    Cooney, Lewis; Hawcutt, Daniel; Sinha, Ian

    2016-01-01

    Intravenous theophyllines are a second line treatment for children suffering an acute exacerbation of asthma. Various guidelines and formularies recommend aiming for serum theophylline levels between 10-20mg/l. This review aims to assess the evidence underpinning this recommendation. A systematic review comparing outcomes of children who achieved serum theophylline concentrations between 10-20mg/l with those who did not. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge, adverse effects and FEV1. MEDLINE, CINAHL, CENTRAL and Web of Science. Search performed in October 2015. Interventional or observational studies utilizing intravenous theophyllines for an acute exacerbation of asthma in children where serum theophylline levels and clinical outcomes were measured. 10 RCTs and 2 observational studies were included. Children with serum levels between 10-20mg/l did not have a reduction in duration of symptoms, length of hospital stay or need for mechanical ventilation or better spirometric results compared with levelsadverse effects. This study is limited due to heterogeneity in the way theophylline levels were reported and poor surveillance of adverse effects across studies. Dosing strategies aiming for levels between 10-20mg/l are not associated with better outcomes. Clinicians should rely on clinical outcomes and not serum levels when using intravenous theophyllines in children suffering an acute exacerbation of asthma.

  13. Target-controlled formation of silver nanoclusters in abasic site-incorporated duplex DNA for label-free fluorescence detection of theophylline.

    Science.gov (United States)

    Park, Ki Soo; Oh, Seung Soo; Soh, H Tom; Park, Hyun Gyu

    2014-09-07

    A novel, label-free, fluorescence based sensor for theophylline has been developed. In the new sensor system, an abasic site-incorporated duplex DNA probe serves as both a pocket for recognition of theophylline and a template for the preparation of fluorescent silver nanoclusters. The strategy relies on theophylline-controlled formation of fluorescent silver nanoclusters from abasic site-incorporated duplex DNA. When theophylline is not present, silver ions interact with the cytosine groups opposite to the abasic site in duplex DNA. This interaction leads to efficient formation of intensely red fluorescent silver nanoclusters. In contrast, when theophylline is bound at the abasic site through pseudo base-pairing with appropriately positioned cytosines, silver ion binding to the cytosine nucleobase is prevented. Consequently, fluorescent silver nanoclusters are not formed causing a significant reduction of the fluorescence signal. By employing this new sensor, theophylline can be highly selectively detected at a concentration as low as 1.8 μM. Finally, the diagnostic capability and practical application of this sensor were demonstrated by its use in detecting theophylline in human blood serum.

  14. Theophylline Represses IL-8 Secretion from Airway Smooth Muscle Cells Independently of Phosphodiesterase Inhibition. Novel Role as a Protein Phosphatase 2A Activator.

    Science.gov (United States)

    Patel, Brijeshkumar S; Rahman, Md Mostafizur; Rumzhum, Nowshin N; Oliver, Brian G; Verrills, Nicole M; Ammit, Alaina J

    2016-06-01

    Theophylline is an old drug experiencing a renaissance owing to its beneficial antiinflammatory effects in chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Multiple modes of antiinflammatory action have been reported, including inhibition of the enzymes that degrade cAMP-phosphodiesterase (PDE). Using primary cultures of airway smooth muscle (ASM) cells, we recently revealed that PDE4 inhibitors can potentiate the antiinflammatory action of β2-agonists by augmenting cAMP-dependent expression of the phosphatase that deactivates mitogen-activated protein kinase (MAPK)-MAPK phosphatase (MKP)-1. Therefore, the aim of this study was to address whether theophylline repressed cytokine production in a similar, PDE-dependent, MKP-1-mediated manner. Notably, theophylline did not potentiate cAMP release from ASM cells treated with the long-acting β2-agonist formoterol. Moreover, theophylline (0.1-10 μM) did not increase formoterol-induced MKP-1 messenger RNA expression nor protein up-regulation, consistent with the lack of cAMP generation. However, theophylline (at 10 μM) was antiinflammatory and repressed secretion of the neutrophil chemoattractant cytokine IL-8, which is produced in response to TNF-α. Because theophylline's effects were independent of PDE4 inhibition or antiinflammatory MKP-1, we then wished to elucidate the novel mechanisms responsible. We investigated the impact of theophylline on protein phosphatase (PP) 2A, a master controller of multiple inflammatory signaling pathways, and show that theophylline increases TNF-α-induced PP2A activity in ASM cells. Confirmatory results were obtained in A549 lung epithelial cells. PP2A activators have beneficial effects in ex vivo and in vivo models of respiratory disease. Thus, our study is the first to link theophylline with PP2A activation as a novel mechanism to control respiratory inflammation.

  15. Determination of caffeine, theophylline and theobromine in serum and saliva using high-performance liquid chromatography.

    Science.gov (United States)

    Scott, N R; Chakraborty, J; Marks, V

    1984-03-01

    A method is described for the measurement of theobromine, theophylline and caffeine in serum and saliva by high-performance liquid chromatography (HPLC). A chloroform/isopropanol extract (85:15, v/v) is evaporated to dryness and chromatographed on a 100 X 4.5 mm id Hypersil octadecylsilane column with UV detection at 280 nm. Theobromine, theophylline, caffeine and the internal standard proxyphylline are satisfactorily resolved with an elution system of acetonitrile/tetrahydrofuran/50 mM acetate buffer, pH 4.0, (4:1:95, v/v). No interference is observed from the presence of xanthine metabolites or any of a number of common drugs examined. A good correlation was observed between the concentrations of caffeine in serum and in saliva suggesting that salivary measurements may be useful for the study of caffeine pharmacokinetics in man. Caffeine levels determined by the HPLC procedure described here agreed well with those obtained by a radioimmunoassay method. The method is also suitable for determining the xanthine content of beverages by direct injection of diluted samples.

  16. Simultaneous HPLC determination of caffeine, theobromine, and theophylline in food, drinks, and herbal products.

    Science.gov (United States)

    Srdjenovic, Branislava; Djordjevic-Milic, Vukosava; Grujic, Nevena; Injac, Rade; Lepojevic, Zika

    2008-02-01

    A rapid and selective high-performance liquid chromatographic (HPLC) method is developed for the separation and determination of caffeine, theobromine, and theophylline. The chromatography is performed on a Zorbax Eclipse XDB-C8 column (4.6x150 mm i.d., 5-microm particle size) at 25 degrees C, with a mobile phase of water-THF (0.1% THF in water, pH 8)-acetonitrile (90:10, v/v). The flow rate is 0.8 mL/min, and detection is by UV at 273 nm. This method permits the simultaneous determination of caffeine, theobromine, and theophylline in food, drinks, and herbal products with detection limits of 0.07-0.2 mg/L and recoveries of 100.20-100.42%. Correlation coefficients, for the calibration curves in the linear range of 0.2-100 mg/L, are greater than 0.9999 for all compounds. The within- and between-day precision is determined for both retention times and peak area. The data suggests that the proposed HPLC method can be used for routine quality control of food, drinks, and herbal products.

  17. Simultaneous determination of caffeine, theobromine, and theophylline by high-performance liquid chromatography.

    Science.gov (United States)

    Bispo, Marcia S; Veloso, Márcia Cristina C; Pinheiro, Heloísa Lúcia C; De Oliveira, Rodolfo F S; Reis, José Oscar N; De Andrade, Jailson B

    2002-01-01

    This work relates the development of an analytical methodology to simultaneously determine three methylxanthines (caffeine, theobromine, and theophylline) in beverages and urine samples based on reversed-phase high-performance liquid chromatography. Separation is made with a Bondesil C18 column using methanol-water-acetic acid or ethanol-water-acetic acid (20:75:5, v/v/v) as the mobile phase at 0.7 mL/min. Identification is made by absorbance detection at 273 nm. Under optimized conditions, the detection limit of the HPLC method is 0.1 pg/mL for all three methylxanthines. This method is applied to urine and to 25 different beverage samples, which included coffee, tea, chocolate, and coconut water. The concentration ranges determined in the beverages and urine are: theobromine; < 0.1 pg/mL to 47 microg/mL and < 0.1 pg/mL to 66.3 microg/mL for theophylline. The method proposed in this study is rapid and suitable for the simultaneous quantitation of methylxanthines in beverages and human urine samples and requires no extraction step or derivatization.

  18. Vibrational spectral investigation on xanthine and its derivatives--theophylline, caffeine and theobromine.

    Science.gov (United States)

    Gunasekaran, S; Sankari, G; Ponnusamy, S

    2005-01-01

    A normal coordinate analysis has been carried out on four compounds having a similar ring structure with different side chain substitutions, which are xanthine, caffeine, theophylline, and theobromine. Xanthine is chemically known as 2,6-dihydroxy purine. Caffeine, theophylline and theobromine are methylated xanthines. Considering the methyl groups as point mass, the number of normal modes of vibrations can be distributed as Gamma(vib) = 27 A' + 12 A" based on C(s) point group symmetry associated with the structures. In the present work 15 A' and 12 A'' normal modes are considered. A new set of orthonormal symmetry co-ordinates have been constructed. Wilson's F-G matrix method has been adopted for the normal coordinate analysis. A satisfactory vibrational band assignment has been made by employing the FTIR and FT Raman spectra of the compounds. The potential energy distribution is calculated with the arrived values of the force constants and hence the agreement of the frequency assignment has been checked.

  19. Simultaneous determination of caffeine, theophylline and theobromine in food samples by a kinetic spectrophotometric method.

    Science.gov (United States)

    Xia, Zhenzhen; Ni, Yongnian; Kokot, Serge

    2013-12-15

    A novel kinetic spectrophotometric method was developed for the simultaneous determination of caffeine, theobromine and theophylline in food samples. This method was based on the different kinetic characteristics between the reactions of analytes with cerium sulphate in sulphuric acid and the associated change in absorbance at 320 nm. Experimental conditions, the effects of sulphuric acid, cerium sulphate and temperature, were optimised. Linear ranges (0.4-8.4 μg mL(-1)) for all three analytes were established, and the limits of detection were: 0.30 μg mL(-1) (caffeine), 0.33 μg mL(-1) (theobromine) and 0.16 μg mL(-1) (theophylline). The recorded data were processed by partial least squares and artificial neural network, and the developed mathematical models were then used for prediction. The proposed, novel method was applied to determine the analytes in commercial food samples, and there were no significant differences between the results from the proposed method and those obtained by high-performance liquid chromatography. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Degradation behavior of theophylline/chitosan/β-cyclodextrin microspheres for pulmonary drug delivery

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-04-01

    Full Text Available To evaluate the degradation behavior of theophylline/chitosan/β-cyclo-dextrin microspheres, we performed both in vitro study by putting the microspheres in phosphate buffered saline or in phosphate buffer saline with enzyme and in vivo study by implanting the microspheres into the back of male Sprague-Dawley rats. The results showed that microspheres were degraded in enzymatic hydrolysis and phosphate buffer saline, which were degraded faster in 0.2 mg/mL lysozyme than in phosphate buffer saline. The morphology of microspheres in phosphate buffer saline and enzyme solution developed rough surfaces, and showed irregular shape and pores after 8 weeks. The microspheres were degraded in vivo within 8 weeks with irregular, sheet, porous morphology, and the diameters were smaller than 5 μm. These results indicated that the theophylline/chitosan/β-cyclodextrin microspheres had a good degradation both in vitro and in vivo which can be used as a pulmonary drug delivery carrier.

  1. Clinical and genetic features of acute encephalopathy in children taking theophylline.

    Science.gov (United States)

    Saitoh, Makiko; Shinohara, Mayu; Ishii, Atsushi; Ihara, Yukiko; Hirose, Shinichi; Shiomi, Masashi; Kawawaki, Hisashi; Kubota, Masaya; Yamagata, Takanori; Miyamoto, Akie; Yamanaka, Gaku; Amemiya, Kaoru; Kikuchi, Kenjiro; Kamei, Atsushi; Akasaka, Manami; Anzai, Yuki; Mizuguchi, Masashi

    2015-05-01

    Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD. We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD. We analyzed the polymorphisms or mutations of genes which are associated with AESD. Clinically, 12 patients had neurological and/or radiological features of AESD. Only one patient died, whereas all 15 surviving patients were left with motor and/or intellectual deficits. Genetically, 14 patients had at least one of the following polymorphisms or mutations associated with AESD: thermolabile variation of the carnitine palmitoyltransferase 2 (CPT2) gene, polymorphism causing high expression of the adenosine receptor A2A (ADORA2A) gene, and heterozygous missense mutation of the voltage gated sodium channel 1A (SCN1A) and 2A (SCN2A) gene. Our results demonstrate that AET overlaps with AESD, and that AET is a multifactorial disorder sharing a genetic background with AESD. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  2. The re-design of a theophylline riboswitch for DNT sensing

    Science.gov (United States)

    Chushak, Yaroslav; Kelley-Loughnane, Nancy; Harbaugh, Svetlana; Stone, Morley

    2008-03-01

    Riboswitches are noncoding elements of mRNA that recognize and bind to small molecules and regulate the translation process of downstream genes. As an initial study, we used a theophylline riboswitch that regulates the expression of the Tobacco etch virus (TEV) protease placed downstream of the switch as a controlling element. Upon expression of TEV protease, an optical reporter is cleaved producing change in fluorescence resonance energy transfer (FRET) between BFP and eGFP. We altered the sensing domain of the original construct to create a synthetic riboswitch that responds to the presence of 2,4-dinitrotoluene (DNT) molecules. Computational analysis using Autodock4 and AMBER9 software packages showed that U24A mutant has a significantly higher binding affinity for DNT molecule compared to the original theophylline. Cells expressing the re-designed riboswitch showed a marked optical difference in fluorescence emission in the presence of DNT molecules, leading to the potential of using this construct in biosentinel applications of highly nitrated compounds.

  3. Pharmacokinetic changes of unbound theophylline are due to plasma protein binding displacement and CYP1A2 activity inhibition by baicalin in rats.

    Science.gov (United States)

    Gao, Na; Fang, Yan; Qi, Bing; Jia, Lin-jing; Jin, Han; Qiao, Hai-ling

    2013-11-25

    Baicalin is one of the major bioactive constituents of Scutellariae Radix, the root of Scutellariae baicalensis Georgi and possesses a wide variety of pharmacological properties. To elucidate the effect of baicalin on the pharmacokinetics of theophylline in rats, focusing on plasma protein binding displacement and inhibition effect on CYP1A2 in vivo and in vitro. The study was a randomized, three-period crossover design. Nine rats were given saline (control) or 450 mg/kg baicalin (dosage regimen A or B). Dosage regimen A was administered once at 0 h. Dosage regimen B was divided into three dosages (225,112.5, 112.5 mg/kg) and was given at 0, 2 and 4 h, respectively. Then theophylline (5 mg/kg, i.v.) was administered immediately. The effect of baicalin on CYP1A2 activity was determined by metabolism of phenacetin in vitro and plasma protein binding of theophylline was determined by ultrafiltration. C(max) decreased from (12.4 ± 1.6) to (8.7 ± 0.9) and (8.6 ± 2.0) mg/L, T(1/2) increased by 116 and 96%, V(d) increased by 51 and 49% for total theophylline in rats treated with dosage regimen A and B of baicalin, respectively. Cmax was significantly increased, V(d) decreased by 43 and 29% for unbound theophylline in rats treated with dosage regimen A and B of baicalin, respectively (P theophylline increased by 104% only in rats treated with dosage regimen B. No significant effects on the CL and AUC of both total and unbound theophylline were observed in the rats treated with dosage regimen A, but the CL decreased and AUC increased for total theophylline and CL decreased for unbound theophylline in the group treated with dosage regimen B (P theophylline (%) and mean baicalin concentration was in good correlation (P theophylline from plasma protein in vitro. The changes in Cmax, T(1/2), CL and AUC of theophylline due to baicalin may be attributed to two mechanisms, plasma protein binding displacement and CYP1A2 activity inhibition. © 2013 Elsevier Ireland Ltd. All

  4. Determination of caffeine, theobromine, and theophylline in standard reference material 2384, baking chocolate, using reversed-phase liquid chromatography.

    Science.gov (United States)

    Thomas, Jeanice Brown; Yen, James H; Schantz, Michele M; Porter, Barbara J; Sharpless, Katherine E

    2004-06-02

    A rapid and selective isocratic reversed-phase liquid chromatographic method has been developed at the National Institute of Standards and Technology to simultaneously measure caffeine, theobromine, and theophylline in a food-matrix standard reference material (SRM) 2384, Baking Chocolate. The method uses isocratic elution with a mobile phase composition (volume fractions) of 10% acetronitrile/90% water (pH adjusted to 2.5 using acetic acid) at a flow rate of 1.5 mL/min with ultraviolet absorbance detection (274 nm). Total elution time for these analytes is less than 15 min. Concentration levels of caffeine, theobromine, and theophylline were measured in single 1-g samples taken from each of eight bars of chocolate over an eight-day period. Samples were defatted with hexane, and beta-hydroxyethyltheophylline was added as the internal standard. The repeatability for the caffeine, theobromine, and theophylline measurements was 5.1, 2.3, and 1.9%, respectively. The limit of quantitation for all analytes was theobromine, and theophylline in SRM 2384.

  5. Theophylline and cAMP inhibit lysophosphatidic acid-induced hyperresponsiveness of bovine tracheal smooth muscle cells

    Science.gov (United States)

    Sakai, Jiro; Oike, Masahiro; Hirakawa, Masakazu; Ito, Yushi

    2003-01-01

    We have established an in vitro model of airway hyperresponsiveness, using a bovine tracheal smooth muscle cell (BTSMC)-embedded collagen gel lattice. When the gel was pretreated with lysophosphatidic acid (LPA), which activates the small G protein RhoA, ATP- and high K+ solution-induced gel contraction was significantly augmented. This was not due to the modulation of Ca2+ mobilizing properties, since ATP- and high K+-induced Ca2+ transients were not significantly different between control and LPA-treated BTSMC. Y-27632, an inhibitor of Rho-kinase, suppressed the LPA-induced augmentation of gel contraction, whereas it did not inhibit the contraction of control gels. Theophylline (> 1 μm) reversed the LPA-induced augmentation of gel contraction, whereas it inhibited control gel contraction only with a very high concentration (100 μm). We confirmed that theophylline increased the intracellular concentration of cAMP ([cAMP]i) in BTSMC. Elevation of [cAMP]i with dibutyryl cAMP or forskolin also reversed the LPA-induced augmentation of gel contraction. Furthermore, theophylline, as well as dibutyryl cAMP and forskolin, suppressed the LPA-induced membrane translocation of RhoA, indicating that they prevented airway hyperresponsiveness by inhibiting RhoA. We conclude from these results that theophylline inhibits LPA-induced, RhoA/Rho-kinase-mediated hyperresponsiveness of tracheal smooth muscle cells due to the accumulation of cAMP. PMID:12679373

  6. Theophylline Pharmacokinetics in Foetal Sheep: Maternal Metabolic Capacity is the Principal Driver.

    Science.gov (United States)

    DuBois, Barent; Louey, Samantha; Giraud, George D; Cherala, Ganesh; Jonker, Sonnet S

    2015-10-01

    Understanding theophylline pharmacokinetics (PK) in the foetus is essential to prevent in utero toxicity and optimize prophylactic therapies. Previous studies in pregnancy have been obfuscated by maternal dosing and inadequate sampling in the foetus; both render modelling of foetal PK difficult. Six ewes carrying singleton foetuses received theophylline (60 mg) into the foetal jugular vein. Blood samples were drawn from the foetus and ewe over 36 hr. Serum concentrations were measured. Maternal and foetal pharmacokinetic parameters were estimated. Foetal non-compartmental pharmacokinetic parameters were as follows: half-life 7.37 ± 1.22 hr; volume of distribution 44.62 ± 11.45 L; area under the curve 14.82 ± 2.71 hr/(μg/mL); and clearance 4.15 ± 0.70 L/hr. Rapid theophylline distribution across the placenta was observed. Maternal non-compartmental pharmacokinetic parameters were as follows: half-life 6.54 ± 2.44 hr; volume of distribution 32.48 ± 9.99 L; area under the curve 16.28 ± 4.53 hr/(μg/mL); and clearance 3.69 ± 1.47 L/hr. Foetal and ewe serum concentration-time profiles were fit together into a 3-compartment population pharmacokinetic model, and parameters were as follows: central volume 1.38 ± 0.11 L; 2nd peripheral compartment volume 3.11 ± 0.29 L; 3rd peripheral compartment volume 60.14 ± 6.02 L; elimination clearance 9.89 ± 0.90 L/hr; distribution clearance between central and 2nd compartment 30.87 ± 2.31 L/hr; and distribution clearance between 2nd and 3rd compartments 13.89 ± 1.11 L/hr. Cytochrome P4501A expression was robust in maternal liver; negligible activities were observed in placenta, foetal liver and foetal kidney. In vitro protein binding of theophylline was 30% lower in foetal serum compared to maternal serum (29.7 ± 4.4 versus 42.0 ± 3.6%-bound). Free concentrations were lower in the foetus than in the ewe, suggesting active transport across placenta. In summary, foetal

  7. Effect of theophylline on the rate of moderate to severe exacerbations among patients with chronic obstructive pulmonary disease

    Science.gov (United States)

    Cyr, Marie-Christyne; Beauchesne, Marie-France; Lemière, Catherine; Blais, Lucie

    2008-01-01

    AIM To determine the effectiveness of theophyllines in real clinical practice on moderate to severe exacerbations. METHODS A cohort of 36 492 chronic obstructive pulmonary disease (COPD) patients aged ≥50 years was reconstructed from the health administrative databases of the province of Quebec, Canada, between 1 January 1995 and 31 December 2002 to compare users of theophyllines with users of inhaled corticosteroids (ICS) and users of long-acting β2-agonists (LABA) on their rate of moderate to severe COPD exacerbations. RESULTS Users of theophyllines were found to be less likely than users of LABA [crude rates 84 vs. 91 per 100 patient-years, adjusted rate ratio (RR) 0.89, 95% confidence interval (CI) 0.84, 0.95] and users of theophyllines plus ICS were found to be less likely than users of LABA plus ICS (crude rates 114 vs. 112 per 100 patient-years, adjusted RR 0.89, 95% CI 0.87, 0.92) to have moderate to severe COPD exacerbations. Users of theophyllines were found to be more likely than users of ICS to have a COPD exacerbation (crude rates 84 vs. 77 per 100 patient-years, adjusted RR 1.07, 95% CI 1.04, 1.10), and this association was even stronger among patients who had at least three exacerbations in the year prior to cohort entry (crude rates 273 vs. 213 per 100 patient-years, adjusted RR 1.28, 95% CI 1.19, 1.38). CONCLUSION The use of theophyllines was found to be associated with a reduction in the rate of COPD exacerbations among all COPD patients, but to be less effective than ICS among patients with frequent exacerbations. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Despite active research, none of the existing medications used to treat chronic obstructive pulmonary disease (COPD) has been shown to modify the long-term decline in lung function. Theophyllines have been recognized for their bronchodilating effects and anti-inflammatory properties, but at the same time they are associated with the risk of adverse events due to their narrow therapeutic range

  8. Prevention of contrast-induced acute kidney injury by theophylline in elderly patients with chronic kidney disease.

    Science.gov (United States)

    Matejka, Jan; Varvarovsky, Ivo; Vojtisek, Petr; Herman, Ales; Rozsival, Vladimir; Borkova, Veronika; Kvasnicka, Jiri

    2010-11-01

    Although the optimal strategy for preventing contrast-induced acute kidney injury (CI-AKI) has not yet been established, the current strategy focuses on adequate periprocedural hydration, the use of a low amount of low or iso-osmolar contrast medium, and the application of adjunctive therapies, including hemofiltration, hemodialysis and drugs. Previous trials and meta-analyses concerning the use of the adenosine antagonist theophylline have revealed contradictory results. We sought to evaluate the effect of theophylline in CI-AKI prevention in well-hydrated elderly patients with chronic kidney disease. We therefore conducted a randomized, double-blind, placebo-controlled trial involving 56 patients who had been referred for cardiac coronary angiography and/or angioplasty. 31 of these patients were randomly assigned to 200 mg theophylline IV before the procedure, and 25 to a placebo. The iso-osmolar contrast medium iodixanol was used. The primary endpoint was an increase in serum creatinine at study termination 48 h after contrast medium administration. Baseline characteristics in the placebo and theophylline groups were similar in terms of median age (75 years), estimated glomerular filtration rate (33 ± 10 vs. 33 ± 10 ml/min/1.73 m²; p = 0.87), diabetes mellitus (80 vs. 71%; p = 0.54), and amount of contrast used (94 ± 35 vs. 95 ± 38 ml; p = 0.89). There was no difference in serum creatinine at baseline (2.06 ± 0.59 vs. 2.02 ± 0.45 mg/dl; p = 0.62) or study termination (2.06 ± 0.68 vs. 2.10 ± 0.53; p = 0.79). A prophylactic effect of theophylline was not observed. The incidence of renal impairment following exposure to the contrast medium was low. This fact can be attributed to adequate parenteral hydratation and the use of the minimum amount of contrast medium necessary.

  9. [Rapid determination of theophylline, theobromine and caffeine in dietary supplements containing guarana by ultra-performance liquid chromatography].

    Science.gov (United States)

    Hasegawa, Takashi; Takahashi, Kazunaga; Saijo, Masaaki; Ishii, Toshiyasu; Nagata, Tomoko

    2009-12-01

    A rapid and simple method for determination of theophylline, theobromine and caffeine in dietary supplements containing guarana by ultra-performance liquid chromatography (UPLC) has been developed. Theophylline, theobromine and caffeine were extracted from finely powdered samples with water in a boiling water bath for 20 min, then the extracts were filtered and the filtrates were subjected to UPLC. Liquid samples were diluted with water and filteres, and the filtrates were subjected to UPLC. UPLC separation was performed on an AQUITY UPLC BEH C18 column (2.1 mm i.d.x50 mm, 1.7 microm, Waters) with 10 mmol/L ammonium acetate buffer (pH 4.0)-acetonitrile gradient and eluates were monitored at 275 nm. The recoveries of theophylline (spiked at 200 microg/g [tablet] and 50 microg/mL [liquid]), theobromine (spiked at 200 microg/g [tablet] and 50 microg/mL [liquid]) and caffeine (spiked at 1,000 microg/g [tablet] and 250 microg/mL [liquid]) were 97.6-98.7%, 97.3-99.7%, 97.1-105.4%, respectively. The quantitation limits of theophylline, theobromine and caffeine were 10 microg/g (seed, seed powder, tablet and capsule) and 2.0 microg/mL (liquid) each. When this analytical method was applied to commercial dietary supplements, theophylline, theobromine and caffeine were found at concentrations of 4.45 mg/tablet, 5.48 mg/tablet, 139 mg/tablet, respectively. Taking 4 tablets of this product according to the directions on the package could be dangerous to consumers because of possible overdosing of these ingredients.

  10. Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study

    Science.gov (United States)

    Voduc, Nha; Alvarez, Gonzalo G; Amjadi, Kayvan; Tessier, Caroline; Sabri, Elham; Aaron, Shawn D

    2012-01-01

    Background Many patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results. Methods We performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy. Results Analyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: −17.3–69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77–21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups. Conclusions Our study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration. PMID:22563244

  11. Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers.

    Science.gov (United States)

    Wang, Liqing; Hu, Zheyi; Deng, Xun; Wang, Yong; Zhang, Zhongyi; Cheng, Ze-Neng

    2013-04-01

    This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese population. Four polymorphisms CYP1A2 1C (G-3860A), G-3113A, CYP1A2 1F (C-163A) and CYP1A2 1B (C-5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200-mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17X/137X) after administration of 100-mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high-performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the -3113 AA genotype compared with those with the -3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the -3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2 1F polymorphisms were associated with increased CYP1A2 activity in volunteers with -3860G/-3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

  12. Impact of formulation and process variables on solid-state stability of theophylline in controlled release formulations.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval; Mohammad, Adil; Wu, Suyang; Siddiqui, Akhtar; Khan, Mansoor A

    2016-02-29

    Understanding the impact of pharmaceutical processing, formulation excipients and their interactions on the solid-state transitions of pharmaceutical solids during use and in storage is critical in ensuring consistent product performance. This study reports the effect of polymer viscosity, diluent type, granulation and granulating fluid (water and isopropanol) on the pseudopolymorphic transition of theophylline anhydrous (THA) in controlled release formulations as well as the implications of this transition on critical quality attributes of the tablets. Accordingly, 12 formulations were prepared using a full factorial screening design and monitored over a 3 month period at 40 °C and 75%. Physicochemical characterization revealed a drastic drop in tablet hardness accompanied by a very significant increase in moisture content and swelling of all formulations. Spectroscopic analysis (ssNMR, Raman, NIR and PXRD) indicated conversion of THA to theophylline monohydrate (TMO) in all formulations prepared by aqueous wet granulation in as early as two weeks. Although all freshly prepared formulations contained THA, the hydration-dehydration process induced during aqueous wet granulation hastened the pseudopolymorphic conversion of theophylline during storage through a cascade of events. On the other hand, no solid state transformation was observed in directly compressed formulations and formulations in which isopropanol was employed as a granulating fluid even after the twelve weeks study period. The transition of THA to TMO resulted in a decrease in dissolution while an increase in dissolution was observed in directly compressed and IPA granulated formulation. Consequently, the impact of pseudopolymorphic transition of theophylline on dissolution in controlled release formulations may be the net result of two opposing factors: swelling and softening of the tablets which tend to favor an increase in drug dissolution and hydration of theophylline which decreases the drug

  13. Aspirin attenuates the anti-inflammatory effects of theophylline via inhibition of cAMP production in mice with non-eosinophilic asthma

    National Research Council Canada - National Science Library

    Moon, Hyung-Geun; Kim, You-Sun; Choi, Jun-Pyo; Choi, Dong-Sic; Yoon, Chang Min; Jeon, Seong Gyu; Gho, Yong Song; Kim, Yoon-Keun

    2010-01-01

    ... 20% of patients with asthma experience aggravated respiratory symptoms after taking ASA. Here we evaluated the adverse effect of ASA on the therapeutic effect of theophylline in mice with non-eosinophilic asthma...

  14. Combination of First Derivative Spectrophotometry and H-Point Standard Addition Method for Simultaneous Determination of Guaifenesin and Theophylline in Cough Syrup

    Directory of Open Access Journals (Sweden)

    R. Hajian

    2011-01-01

    Full Text Available Combination of first derivative spectrophotometric and H-point standard addition method (HPSAM has been applied for simultaneous determination of guaifenesin and theophylline. First derivative signals at the two pairs of wavelengths, 282.0-290.2 nm and 277.4-287.8 nm were monitored with the addition of standard solutions of both guaifenesin and theophylline in the ratio of 1:1. The method is able to accurately determine guaifenesin and theophylline (1:5 to 10:1 mole ratios. Accuracy and reproducibility of the determination method on the various amounts of guaifenesin and theophylline with known concentrations were evaluated in their binary mixtures. The recommended procedure was successfully applied to some cough syrups and synthetic mixtures with satisfactory results.

  15. Addition of Theophylline or Increasing the Dose of Inhaled Corticosteroid in Symptomatic Asthma: A Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Liao, Xiuqing

    2011-01-01

    Purpose Low-dose theophylline has anti-inflammatory effects. The aim of this study was to evaluate the effects of adding theophylline compared with increasing the dose of inhaled corticosteroid (ICS) on symptomatic asthma. Materials and Methods The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. The extracted data were further analyzed by a meta-analysis Results Four randomized, controlled, parallel studies were selected. Addition of theophylline produced a greater increase of forced expiratory volume in one second as %predicted (FEV1pred) by 2.49% [95% confidence interval (CI) 1.99-3.00; z = 9.70; p theophylline to ICS has similar therapeutic effects on improving lung function as increasing the dose of ICS in the treatment of symptomatic asthma. PMID:21319345

  16. The effect of chronic cadmium exposure on the pharmacokinetics of theophylline and ciprofloxacin in rats.

    Science.gov (United States)

    Zaghloul, Iman Y; Radwan, Mahasen A; Aly, Zinat H

    2007-01-01

    Cadmium has been associated with a number of adverse health effects but the impact of those effects on the pharmacokinetics of different drugs has not been investigated. Therefore, the pharmacokinetics of theophylline and ciprofloxacin were studied in cadmium-exposed and control rats (72 rats) following i.p. (6.5mg/kg) and p.o. (10mg/kg) administration, respectively. The third-generation offsprings of rats exposed to 100 microg/mL of cadmium chloride in drinking water were used in this study. Following 8 weeks of exposure, animals received the drugs as a single dose. Blood samples were withdrawn at different time-points and the plasma concentrations of both drugs were analyzed by HPLC. The pharmacokinetic parameters of theophylline and ciprofloxacin were altered significantly in the cadmium-exposed animals. For theophylline, a statistically significant increase (ptheophylline in the cadmium-exposed rats as compared to the control were observed. A corresponding significant (ptheophylline was detected in the exposed group. Neither the half-life nor the mean residence time (MRT) showed any significant change due to the exposure to cadmium. For ciprofloxacin, no significant difference was seen in the C(max) of the exposed group as compared to the control animals. However, a delay in T(max) was observed in the exposed group (from 0.16(+/-0.003) to 0.37(+/-0.14)h). A small, but significant increase in t(1/2) (p<0.05) was detected (1.74(+/-0.25) vs. 1.45(+/-0.12)h). A significant reduction (p<0.05) of CL/F from 30.54(+/-1.9) to 24.01(+/-3.81)mL/min/kg was seen in the treated group. The current investigation showed that chronic exposure to cadmium could have a very significant impact on altering the pharmacokinetic parameters of various drugs. Therefore, in cadmium-polluted areas, dose adjustments and drug monitoring, especially for drugs with a narrow therapeutic window, should be carried out.

  17. In vitro study on the interaction of ketotifen fumarate with anhydrous theophylline

    Directory of Open Access Journals (Sweden)

    Mohammed Aktar Sayeed

    2012-06-01

    Full Text Available The purpose of the present study was to investigate the interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH (1.2 and 6.8. Using Job's continuous-variation analysis and Ardon's spectrophotomeric measurement methods, the values of the stability constants of theophylline with ketotifen were determined at a fixed temperature (37 ºC at various pH. The stability constants, ranging between 5.66 and 9.92, were derived from Ardon's plot, indicating that comparatively stable complexes had formed as a result of an interaction between the drugs. However, following the interaction of theophylline with ketotifen, stability constants were O objetivo do presente estudo foi investigar a interação entre o fumarato de cetotifeno e a teofilina anidra em meios aquosos com vários pH (1,2 e 6,8. Utilizando a análise da variação contínua de Job e os métodos de medida espectrofotométrica de Ardon, os valores das constantes de estabilidade da teofilina com o cetotifeno foram determinados em temperatura fixa (37 oC em vários pH. As constantes de estabilidade, variando entre 5,66 e 9,92 derivaram-se a partir do delineamento de Ardon, indicando, comparativamente, que complexos estáveis se formaram como resultado da interação entre os fármacos. Entretanto, seguindo a interação da teofilina com o cetotifeno, as constantes de estabilidade foram <1, em pH gástrico (1,2 e intestinal (8,8. A administração concomitante de cetotifeno e teofilina poderia resultar na formação de complexo estável, o que reduz a atividade terapêutica de ambos os fármacos.

  18. Sodium Bicarbonate Prevents Contrast-Induced Nephropathy in Addition to Theophylline: A Randomized Controlled Trial.

    Science.gov (United States)

    Huber, Wolfgang; Huber, Toni; Baum, Stephan; Franzen, Michael; Schmidt, Christian; Stadlbauer, Thomas; Beitz, Analena; Schmid, Roland M; Schmid, Sebastian

    2016-05-01

    In this study, we investigated whether hydration with sodium bicarbonate is superior to hydration with saline in addition to theophylline (both groups) in the prophylaxis of contrast-induced nephropathy (CIN). It was a prospective, randomized, double-blinded study in a university hospital on 2 general intensive care units (63% of investigations) and normal wards.After approval of the local ethics committee and informed consent 152 patients with screening serum creatinine ≥1.1 mg/dL and/or at least 1 additional risk factor for CIN undergoing intravascular contrast media (CM) exposure were randomized to receive a total of 9 mL/kg bicarbonate 154 mmol/L (group B; n = 74) or saline 0.9% (group S; n = 78) hydration within 7 h in addition to intravenous application of 200 mg theophylline. Serum creatinine was determined immediately before, 24 and 48 h after CM exposure. As primary endpoint we investigated the incidence of CIN (increase of serum creatinine ≥0.5 mg/dL and/or ≥25% within 48 h of CM).Both groups were comparable regarding baseline characteristics. Incidence of CIN was significantly less frequent with bicarbonate compared to sodium hydration (1/74 [1.4%] vs 7/78 [9.0%]; P = 0.035). Time course of serum creatinine was more favorable in group B with decreases in serum creatinine after 24 h (-0.084 mg/dL [95% confidence interval: -0.035 to -0.133 mg/dL]; P = 0.008) and 48 h (-0.093 mg/dL (-0.025 to -0.161 mg/dL); P = 0.007) compared to baseline which were not observed in group S.In patients at increased risk of CIN receiving prophylactic theophylline, hydration with sodium bicarbonate reduces contrast-induced renal impairment compared to hydration with saline.

  19. Engineering an inducible gene expression system for Bacillus subtilis from a strong constitutive promoter and a theophylline-activated synthetic riboswitch.

    Science.gov (United States)

    Cui, Wenjing; Han, Laichuang; Cheng, Jintao; Liu, Zhongmei; Zhou, Li; Guo, Junling; Zhou, Zhemin

    2016-11-22

    Synthetic riboswitches have been increasingly used to control and tune gene expression in diverse organisms. Although a set of theophylline-responsive riboswitches have been developed for bacteria, fully functional expression elements mediated by synthetic riboswitches in Bacillus subtilis are rarely used because of the host-dependent compatibility between the promoters and riboswitches. A novel genetic element composed of the promoter P43 and a theophylline-riboswitch was developed and characterized in B. subtilis. When combined with a P43 promoter (P43'-riboE1), the theophylline-riboswitch successfully switched the constitutive expression pattern of P43 to an induced pattern. The expression mediated by the novel element could be activated at the translational level by theophylline with a relatively high induction ratio. The induction ratios for P43'-riboE1 by 4-mM theophylline were elevated during the induction period. The level of induced expression was dependent on the theophylline dose. Correspondingly, the induction ratios gradually increased in parallel with the elevated dose of theophylline. Importantly, the induced expression level was higher than three other strong constitutive promoters including PsrfA, PaprE, and the native P43. It was found that the distance between the SD sequence within the expression element and the start codon significantly influenced both the level of induced expression and the induction ratio. A 9-bp spacer was suitable for producing desirable expression level and induction ratio. Longer spacer reduced the activation efficiency. Importantly, the system successfully overexpressed β-glucuronidase at equal levels, and induction ratio was similar to that of GFP. The constructed theophylline-inducible gene expression system has broad compatibility and robustness, which has great potential in over-production of pharmaceutical and industrial proteins and utilization in building more complex gene circuits.

  20. Theophylline as 'add-on' therapy to cetirizine in patients with chronic idiopathic urticaria. A randomized, double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Kalogeromitros, Dimitrios; Kempuraj, Duraisamy; Katsarou-Katsari, Alexandra; Makris, Michael; Gregoriou, Stamatis; Papaliodis, Dean; Theoharides, Theoharis C

    2006-01-01

    Chronic urticaria is a prevalent condition associated with substantial disability. Its pathogenesis is not clearly understood and is divided into autoimmune and chronic idiopathic urticaria (CIU). We investigated if the non-specific phosphodiesterase inhibitor theophylline could provide additional benefit to the histamine-1 receptor (H-1R) antagonist cetirizine in CIU. This was a double-blind, placebo-controlled, parallel study. Patients were randomized to receive either cetirizine and theophylline (200 mg twice daily; group A, 67 subjects) or cetirizine and placebo for 6 months (group B, 67 subjects). Group A patients took theophylline for 6 more months. Response was assessed by visual analog scale (VAS) and treatment effectiveness score (TES). Blood theophylline levels were also determined at visit t=1 and t=7. The study was completed by 54 of the 67 patients (80.6%) in group A and 51 of the 67 patients (76.1%) in group B. The physician VAS values for group A were lower after t=3, while the patient VAS values were decreased after t=2. The physician and patient TES values in group A were statistically higher (ptheophylline addition was necessary to obtain statistically significant benefit over cetirizine, and reducing theophylline by 50% during phase 2 did not alter this benefit. Pruritus values were reduced, but not statistically significant. Addition of theophylline to conventional H-1R antagonists was well tolerated without any adverse effects and provided considerable additional benefit in the management of CIU. Copyright (c) 2006 S. Karger AG, Basel.

  1. Controlled release of tinidazole and theophylline from chitosan based composite hydrogels.

    Science.gov (United States)

    Samanta, Himadri Sekhar; Ray, Samit Kumar

    2014-06-15

    Several composite hydrogels were synthesized by free radical crosslink copolymerization of acrylic acid (AA) and N' methylene bis-acrylamide (MBA) in the presence of chitosan (CS). During polymerization CS was incorporated in situ in the crosslinked polyacrylic acid gel to produce composite hydrogels. The structure and properties of the hydrogels were characterized by FTIR, (13)C NMR, DTA-TGA, XRD, swelling and diffusion characteristic and also network parameters. The loading and the in vitro release behaviours of theophylline and tinidazole model drugs were studied with these hydrogels. The wt% of CS and MBA and pH of the medium was found to strongly influence the drug release behaviour of the gels. Accordingly, the release rate of these two drugs was much faster at pH of 7.6 than at pH 1.5. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Binding of caffeine, theophylline, and theobromine with human serum albumin: A spectroscopic study

    Science.gov (United States)

    Zhang, Hong-Mei; Chen, Ting-Ting; Zhou, Qiu-Hua; Wang, Yan-Qing

    2009-12-01

    The interaction between three purine alkaloids (caffeine, theophylline, and theobromine) and human serum albumin (HSA) was investigated using UV/vis absorption, circular dichroism (CD), fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques. The results revealed that three alkaloids caused the fluorescence quenching of HSA by the formation of alkaloid-HSA complex. The binding site number n and apparent binding constant KA, corresponding thermodynamic parameters the free energy change (Δ G), enthalpy change (Δ H), and entropy change (Δ S) at different temperatures were calculated. The hydrophobic interaction plays a major role in stabilizing the complex. The distance r between donor (HSA) and acceptor (alkaloids) was obtained according to fluorescence resonance energy transfer. The effect of alkaloids on the conformation of HSA was analyzed using circular dichroism (CD), UV/vis absorption, synchronous fluorescence and three-dimensional fluorescence spectra techniques.

  3. Development of a molecularly imprinted polymer based surface plasmon resonance sensor for theophylline monitoring

    Science.gov (United States)

    Zheng, Rui; Cameron, Brent D.

    2011-03-01

    Molecularly imprinted polymer (MIP) thin films and surface plasmon resonance (SPR) sensing technologies were combined to develop a novel sensing platform for monitoring real-time theophylline concentration, which is a compound of interest in environmental monitoring and a molecular probe for phenotyping certain cytochrome P450 enzymes. The MIPs hydrogel is easy to synthesize and provides shape-selective recognition with high affinity to specific target molecules. Different polymerization formulas were tested and optimized. The influence of the monomer sensitive factors were addressed by SPR. SPR is an evanescent wave optics based sensing technique that is suitable for real-time and label free sensing purposes. Gold nanorods (Au NRs) were uniformly immobilized onto a SPR sensing surface for the construction of a fiber optics based prism-free localized SPR (LSPR) measurement. This technique can be also applied to assess the activities of other small organic molecules by adjusting the polymerization formula, thus, this approach also has many other potential applications.

  4. Structural and thermodynamic analysis of the hetero-association of theophylline with aromatic drug molecules

    Science.gov (United States)

    Andrejuk, D. D.; Hernandez Santiago, A. A.; Khomich, V. V.; Voronov, V. K.; Davies, D. B.; Evstigneev, M. P.

    2008-10-01

    The hetero-association of theophylline (THP) with other biologically-active aromatic molecules ( e.g. the anti-cancer drugs daunomycin and novantrone, the antibiotic norfloxacin, the vitamin flavin-mononucleotide and two mutagens ethidium bromide and proflavine) has been studied by NMR in aqueous-salt solution (0.1 M Na-phosphate buffer, p D 7.1). It was found that THP shows an essentially similar hetero-association ability as caffeine (CAF) towards aromatic drugs, except for novantrone (NOV), which has much less affinity to THP than CAF as a result of energetically unfavourable orthogonal orientation of the chromophores of THP and NOV in the hetero-complex.

  5. Synergism of theophylline and anticholinergics to inhibit haloperidol-induced catalepsy: a potential treatment for extrapyramidal syndromes.

    Science.gov (United States)

    González-Lugo, Olga E; Ceballos-Huerta, Fátima; Jiménez-Capdeville, María E; Arankowsky-Sandoval, Gloria; Góngora-Alfaro, José L

    2010-12-01

    Extrapyramidal syndromes (EPS) impose a heavy burden on patients receiving antipsychotic therapy. Anticholinergics are the drugs of choice for preventing EPS, but they also produce many adverse reactions. Using the EPS model of haloperidol-induced catalepsy we evaluated the potential therapeutic value of a mixture of low doses of the non-selective adenosine antagonist theophylline (0.93 and 1.86 mg/kg), and the muscarinic antagonists benztropine (0.134 and 0.268 mg/kg) and ethopropazine (0.116 and 0.232 mg/kg). In rats pretreated with vehicle (distilled water), the cumulative catalepsy time over 5 h was 4199±228 s, and the mean latency was 67.5±7.8 min. Applied separately, neither of the drugs at the doses used caused significant changes of catalepsy intensity vs. control rats. However, the combination of the larger doses of theophylline and benztropine caused a significant reduction of catalepsy intensity (-41±10%) compared with the effects of the vehicle, vs. the lower dose of benztropine, and vs. both doses of theophylline alone. The mixture of the larger doses of theophylline and benztropine also delayed catalepsy onset (156±21 min) as compared with the lower doses of these same drugs applied alone. In the case of theophylline plus ethopropazine, only the association of the larger doses showed a non-significant tendency to inhibit catalepsy (-21±8%) and to prolong its latency (108±13 min). Further, neither catalepsy intensity nor its latency was affected by a combination of the selective A(1)R antagonist DPCPX (1 mg/kg), with the larger doses of both anticholinergics. In contrast, the anticholinergics showed synergism with a subthreshold dose of the selective A(2A)R antagonist ZM 241395 (0.5 mg/kg), causing a significant reduction of catalepsy intensity (ethopropazine, -27±5%; benztropine, -35±9%) and prolonging its latency (ethopropazine, 65±9 min; benztropine, 78±11 min), compared with the effect of their respective vehicle (DMSO plus mineral oil

  6. Theophylline Regulates Inflammatory and Neurotrophic factor Signals in Functional Recovery after C2-Hemisection in Adult Rats

    Science.gov (United States)

    Singh, LP; Devi, TS; Nantwi, KD

    2012-01-01

    Recovery of respiratory activity in an upper cervical hemisection model (C2H) of spinal cord injury (SCI) can be induced by systemic theophylline administration 24–48 h after injury. The objectives in the present study are (1) to identify pro-inflammatory and neurotrophic factors expressed after C2H and (2) molecular signals involved in functional recovery. Four groups of adult female rats classified as (i) sham (SH) controls, (ii) subjected to a left C2 hemisection (C2H) only, (iii) C2H rats administered theophylline for 3 consecutive days 2 days after C2H (C2H-T Day 5) and (iv) C2H rats treated with theophylline for 3 consecutive days 2 days after C2H and then weaned for 12 days (C2H-T Day 17) prior to assessment of respiratory function and molecular analysis were employed. Corresponding Sham controls, C2H untreated (vehicle only controls) and C2H treated (theophylline) rats were sacrificed, C3-C6 spinal cord segments quickly dissected and left (ipsilateral) hemi spinal cord and right (contralateral) hemi spinal cord were separately harvested 2 days post surgery. SHAM operated and C2H untreated-controls corresponding to C2H-T Day 5 and C2H-T Day 17 rats, respectively, were prepared similarly. Messenger RNA levels for pro-inflammatory genes (TXNIP, IL-1β, TNF-α and iNOS) and neurotrophic and survival factors (BDNF, GDNF, and Bcl2) were analyzed by real time quantitative PCR. Gene expression pattern was unaltered in SH rats. TXNIP, iNOS, BDNF, GDNF and Bcl2 mRNA levels were significantly increased in the ipsilateral hemi spinal cord in C2H rats. BDNF, GDNF and Bcl2 levels remained elevated in the ipsilateral hemi spinal cord in C2H-T Day 5 rats. In this same group, there was further enhancement in TXNIP and IL-1β while iNOS returned to basal levels. Theophylline increased DNA binding activity of transcription factors - cyclic AMP responsive element (CRE) binding protein (CREB) and pro-inflammatory NF-κB. Messenger RNA levels for all genes returned to basal

  7. Single crystal, vibrational and computational studies of Theophylline (a bronchodilator drug) and its chloride salt

    Science.gov (United States)

    Mary Novena, L.; Suresh Kumar, S.; Athimoolam, S.; Saminathan, K.; Sridhar, B.

    2017-04-01

    The crystal structure of Theophylline (TH) and Theophyillinium chloride monohydrate (THC) and its complete molecular structure analysis on theoretical and experimental methods is reported here. The hydrogen bonding studies were carried out as a special note of the present work. The electron density analyses of the compounds were also analyzed in view of the intermolecular interactions. Moreover, it is an ever first quantum chemical report of this drug (TH) and its chloride salt. In TH crystal, the water molecule connects the Theophylline molecules through Osbnd H⋯N hydrogen bond forming discrete D22(7) motif and dimeric ring R22(10) motif through Nsbnd H⋯O hydrogen bond. In THC, the two classical (Nsbnd H⋯O, Nsbnd H⋯Cl) and one non-classical (Csbnd H⋯O) hydrogen bonds produce two pentameric chain C55 (16) and C55(17) motifs. These two chain motifs are interconnected by Osbnd H⋯O hydrogen bond and cross linked by Nsbnd H⋯Cl and Osbnd H⋯Cl hydrogen bonds to produce octametric ring R88(27) and R88(28) motifs. The solubility test is carried out to enhance the drug solubility and the therapeutic effectiveness of the drug. Experimentally obtained vibrational wavenumbers are compared with the spectra obtained theoretically for both the compound. The strong intensity bands and the shifting of bands due to intermolecular hydrogen bonds are also investigated. The Mulliken atomic charges, HOMO-LUMO and thermodynamic properties are calculated using Density Functional Theory (DFT) and Hartree-Fock Theory (HF) using 6-311++G(d,p) basis set.

  8. Dissolution profile of theophylline modified release tablets, using a biorelevant Dynamic Colon Model (DCM).

    Science.gov (United States)

    Stamatopoulos, Konstantinos; Batchelor, Hannah K; Simmons, Mark J H

    2016-11-01

    The human proximal colon has been considered a favourable site to deliver drugs for local and systemic treatments. However, modified dosage forms face a complex and dynamically changing colonic environment. Therefore, it has been realized that in addition to the use of biorelevant media, the hydrodynamics also need to be reproduced to create a powerful in vitro dissolution model to enable in vivo performance of the dosage forms to be predicted. A novel biorelevant Dynamic Colon Model (DCM) has been developed which provides a realistic environment in terms of the architecture of the smooth muscle, the physical pressures and the motility patterns occurring in the proximal human colon. Measurements of pressure inside the DCM tube confirmed a direct association between the magnitude of the pressure signal with the occlusion rate of the membrane and the viscosity of the fluid. The dissolution profile and the distribution of the highly soluble drug, theophylline, were assessed by collecting samples at different locations along the DCM tube. Differences in the release rates of the drug were observed which were affected by the sampling point location, the viscosity of the fluid and the mixing within the DCM tube. Images of the overall convective motion of the fluid inside the DCM tube obtained using Positron Emission Tomography enabled relation of the distribution of the tracer to likely areas of high and low concentrations of the theophylline drug. This information provides improved understanding of how extensive phenomena such as supersaturation and precipitation of the drug may be during the passage of the dosage form through the proximal colon. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Study on Effectiveness of Low Dose Theophylline as Add-on to Inhaled Corticosteroid for Patients with Sulfur Mustard Induced Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Yunes Panahi

    2013-12-01

    Full Text Available Background: Theophylline may reverse steroid resistance and decrease inflammation in patients with chronic pulmonary disease and sulfur mustard (SM induced bronchiolitis. This study was designed to assess the effects of low-dose theophylline on improvement of pulmonary function tests (PFTs of SM exposed patients.Methods: In this comparative observational study, a group of SM-exposed victims during the Iraq-Iran war who were treated with oral slow releasing (SR theophylline, salmetrol, fluxitide, omeprazole and NAC (study group were compared to a group of age and gender matched SM-exposed patients who received same medications except oral SR theophylline (historical control group. PFTs were measured at the beginning of the study and after 8 weeks of the treatment.Results: In total, 33 subjects in the study group and 27 subjects in the control group were studied. Mean (SD age of all subjects was 51 (14.1 years. In the study group, on the 8th week post-treatment, PFTs decreased, though the differences of tests between before and after treatment were not significant. In the control group, all the tests decreased in the same period and these reductions were not also significant. However, the changes in PFTs were significantly different between the two groups. The results of most PFTs in the controls decreased in greater extents compared to theophylline treated patients. This shows that despite theophylline was unable to improve the patients; it was partially able to decelerate the reductions in PFTs.Conclusion: Theophylline may not improve PFTs of SM exposed patients but it may decelerate the progress of the underlying respiratory disease. Further studies in this setting with higher doses of theophylline and longer term of evaluation are needed to better understand the pathophysiological mechanism of SM induced bronchiolitis and the effectiveness of the treatment with theophylline.   How to cite this article: Panahi Y, Poursaleh Z, Amini-Harandi A

  10. [Determination of six main components in compound theophylline tablet by convolution curve method after prior separation by column partition chromatography

    Science.gov (United States)

    Zhang, S. Y.; Wang, G. F.; Wu, Y. T.; Baldwin, K. M. (Principal Investigator)

    1993-01-01

    On a partition chromatographic column in which the support is Kieselguhr and the stationary phase is sulfuric acid solution (2 mol/L), three components of compound theophylline tablet were simultaneously eluted by chloroform and three other components were simultaneously eluted by ammonia-saturated chloroform. The two mixtures were determined by computer-aided convolution curve method separately. The corresponding average recovery and relative standard deviation of the six components were as follows: 101.6, 1.46% for caffeine; 99.7, 0.10% for phenacetin; 100.9, 1.31% for phenobarbitone; 100.2, 0.81% for theophylline; 99.9, 0.81% for theobromine and 100.8, 0.48% for aminopyrine.

  11. Design and statistical optimization of an effervescent floating drug delivery system of theophylline using response surface methodology

    Directory of Open Access Journals (Sweden)

    Srikanth Meka Venkata

    2016-03-01

    Full Text Available The aim of this research was to formulate effervescent floating drug delivery systems of theophylline using different release retarding polymers such as ethyl cellulose, Eudragit® L100, xanthan gum and polyethylene oxide (PEO N12K. Sodium bicarbonate was used as a gas generating agent. Direct compression was used to formulate floating tablets and the tablets were evaluated for their physicochemical and dissolution characteristics. PEO based formulations produced better drug release properties than other formulations. Hence, it was further optimized by central composite design. Further subjects of research were the effect of formulation variables on floating lag time and the percentage of drug released at the seventh hour (D7h. The optimum quantities of PEO and sodium bicarbonate, which had the highest desirability close to 1.0, were chosen as the statistically optimized formulation. No interaction was found between theophylline and PEO by Fourier Transformation Infrared spectroscopy (FTIR and Differential Scanning Calorimetry (DSC studies.

  12. Treatment of cyanotic breath-holding spells with oral theophylline in a 10-year-old boy.

    Science.gov (United States)

    Garg, Meenal; Goraya, Jatinder S

    2015-06-01

    Cyanotic breath-holding spells are generally benign and resolve spontaneously by 4 to 5 years of age. Treatment with iron and other drugs has been employed in selected cases with very frequent and severe episodes. We describe a 10-year-old boy with recent-onset cyanotic breath-holding spells that were activity limiting. He was unable to participate in physical activities with his peers as any argument or emotional upset provoked these spells. Treatment with oral iron and piracetam was ineffective. However, treatment with oral theophylline produced dramatic amelioration of symptoms, and he was once again able to participate in play activities with his peers. We believe that general central nervous system stimulant and respirogenic effects of theophylline were instrumental in control of symptoms in our child. © The Author(s) 2014.

  13. A randomized open-label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children.

    Science.gov (United States)

    Kondo, Naomi; Katsunuma, Toshio; Odajima, Yasuhei; Morikawa, Akihiro

    2006-09-01

    Inhaled corticosteroids (ICSs) are widely used in combination with other classes of drugs for treatment of childhood asthma. The efficacy and the safety of montelukast added to low-dose ICS therapy were compared with those of sustained-release theophylline added to low-dose ICS therapy in asthmatic children in the present study. Following the 2-week run-in period, 6-to 14-year old patients receiving treatment with ICSs were randomized to treatment for 4 weeks with either montelukast 5 mg once daily or sustained release theophylline 5-8 mg/kg (dry syrup) or 100-200 mg (tablet) twice daily. Patients also received a fixed dose of ICS throughout the run-in and treatment periods. The primary efficacy endpoint was the change from baseline in peak expiratory flow (PEF) at Week 2. A significant increase in morning PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 2 (change from baseline of 22.8 L/minvs. 8.7 L/min; p = 0.041 for between-group difference) and at Week 4 (31.0 L/minvs. 9.8 L/min; p = 0.012). A significant increase in evening PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 4 (24.7 L/minvs. 8.7 L/min; p = 0.027). There were no significant differences between the treatment groups in incidences of clinical and laboratory adverse experiences. The results indicate that montelukast added to low-dose ICS is an effective and safe option for the treatment of asthma in children.

  14. Histophatologic changes of lung in asthmatic male rats treated with hydro-alcoholic extract of Plantago major and theophylline

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    Farah Farokhi

    2013-03-01

    Full Text Available Objective: Plantago major (P. major is one of the medicinal crops in the world which has therapeutic properties for treatment of respiratory and gastrointestinal diseases. Theophylline is commonly used for the treatment of respiratory diseases. In this study, we investigated the protective effects of hydro-alcoholic extract of P. major on lung in asthmatic male rats. Materials and Methods: 32 male adult rats were randomly divided into 4 groups: The control group (C received normal saline; Asthma (A group received a normal diet; Asthma group treated with Theophylline (200 mg/kg b.w. (T; Asthma group which received p.major (100 mg/kg b.w. (P. Asthma was induced by citric acid, 0.1 mg in form of spraying. The injection of P.major extract and theophylline was administered intraperitoneally for four weeks. At the end of the treatment, all of the rats were sacrificed and lungs were taken out, fixed, and stained with H&E, toluidine blue, and PAS, then histological studies were followed with light microscope. Results: Results showed that, in asthmatic group, the mean number of mast cells was significantly increased (p<0.05. Thickness of alveolar epithelium and accumulation of glycoprotein in airways was increased. Moreover, in some of alveolar sac hemorrhaging was observed. Administration of p.major extract in asthmatic rats restored these changes towards normal group.Conclusion: The present study revealed that P. major compared with theophylline, has a protective effect on lung in asthmatic rats.

  15. Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

    Science.gov (United States)

    Pal, Rishi; Chaudhary, Manju J; Tiwari, Prafulla C; Babu, Suresh; Pant, K K

    2015-12-01

    Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (ptheophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (ptheophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05). Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Use of Resting Cells of Native Screened Rhodotorula sp. CW03 in Biotransformation of Caffeine to Theophylline and Paraxanthine

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    M. Ashengroph

    2015-07-01

    Full Text Available Introduction & Objective: In recent years, microorganisms have been applied as biocatalysts for making pharmaceutically natural products. Microbial biotransformation of caffeine suggests a dual approach for biodegradation of toxic caffeine from polluted environments and a method for the production of medically and pharmaceutically valuable dimethylxanthines. The present work describes the identification of native yeasts capable of biotransformation of caffeine into theophylline and paraxanthine. Materials & Methods: In this experimental study fourteen yeast strains which were able to de-grade caffeine isolated based on their morphology were selected as biocatalysts for biotrans-formation of caffeine as a low-cost substrate to high value added dimethylxanthines such as theophylline and theobromine. The selected strains were characterized based on phenotypic and genetic tests. Screening was performed by Thin Layer Chromatography (TLC and High Performance Liquid Chromatography (HPLC analyses. Results: The results obtained using TLC and HPLC analyses suggest formation of two main metabolites of theophylline and paraxanthine from biotransformation of caffeine under resting cells of Rhodotorula sp. CW03 (GenBank accession number KF414531. The results showed that under resting cell conditions a maximum concentration of theophylline 380 mg/l (molar yield of 16.4% and paraxanthine 880 mg/l (molar yield of 37.9% were obtained after 72 h and 120 h of conversion time, respectively. Conclusion: In the current investigation, done for the first time in Iran, we describe the isola-tion and identification of yeast strains with caffeine degradation ability which can be proposed as safe and cost-effective biocatalysts in production of value added dimethylxanthines from caffeine as a low-cost substrate.(Sci J Hamadan Univ Med Sci 2015; 22 (2: 83-92

  17. Crystal structures of human pyridoxal kinase in complex with the neurotoxins, ginkgotoxin and theophylline: insights into pyridoxal kinase inhibition.

    Science.gov (United States)

    Gandhi, Amit K; Desai, Jigar V; Ghatge, Mohini S; di Salvo, Martino L; Di Biase, Stefano; Danso-Danquah, Richmond; Musayev, Faik N; Contestabile, Roberto; Schirch, Verne; Safo, Martin K

    2012-01-01

    Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B₆, pyridoxal 5'-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B₆ is converted to PLP by PL kinase. PLP is the B₆ vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B₆, or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects.

  18. Crystal structures of human pyridoxal kinase in complex with the neurotoxins, ginkgotoxin and theophylline: insights into pyridoxal kinase inhibition.

    Directory of Open Access Journals (Sweden)

    Amit K Gandhi

    Full Text Available Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase, resulting in deficiency of the active cofactor form of vitamin B₆, pyridoxal 5'-phosphate (PLP. Pyridoxal (PL, an inactive form of vitamin B₆ is converted to PLP by PL kinase. PLP is the B₆ vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B₆, or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects.

  19. Histophatologic changes of lung in asthmatic male rats treated with hydro-alcoholic extract of plantago major and theophylline

    Directory of Open Access Journals (Sweden)

    Farah Farokhi

    2013-04-01

    Full Text Available Objective: Plantago major (P. major is one of the medicinal crops in the world which has therapeutic properties for treatment of respiratory and gastrointestinal diseases. Theophylline is commonly used for the treatment of respiratory diseases. In this study, we investigated the protective effects of hydro-alcoholic extract of P. majoron lung in asthmatic male rats. Materials and Methods: 32 male adult rats were randomly divided into 4 groups: The control group (C received normal saline; Asthma (A group received a normal diet; Asthma group treated with Theophylline (200 mg/kg b.w. (T; Asthma group which received p.major (100 mg/kg b.w. (P. Asthma was induced by citric acid, 0.1 mg in form of spraying. The injection of P.major extract and theophylline was administered intraperitoneally for four weeks. At the end of the treatment, all of the rats were sacrificed and lungs were taken out, fixed, and stained with H&E, toluidine blue, and PAS, then histological studies were followed with light microscope. Results: Results showed that, in asthmatic group, the mean number of mast cells was significantly increased (p

  20. Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition

    Science.gov (United States)

    Ghatge, Mohini S.; di Salvo, Martino L.; Di Biase, Stefano; Danso-Danquah, Richmond; Musayev, Faik N.; Contestabile, Roberto; Schirch, Verne; Safo, Martin K.

    2012-01-01

    Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B6, or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects. PMID:22879864

  1. Novel semi-IPN based on crosslinked carboxymethyl starch and clay for the in vitro release of theophylline.

    Science.gov (United States)

    Anirudhan, T S; Parvathy, J

    2014-06-01

    A novel semi-interpenetrating polymer network (IPN) based on crosslinked carboxymethyl starch (CL-CMS) and montmorillonite (MMT) was prepared, where carboxymethylation occurs as a result of the reaction between native starch and monochloroacetic acid in isopropanol/water medium at 60°C. The carboxymethyl starch is further crosslinked and made into a semi-IPN with MMT for the release of theophylline. The drug carrier was characterized using FTIR, XRD and surface analysis using SEM. Studies including physio-chemical analysis, swelling behavior, encapsulation efficiency, effect of MMT content, effect of ionic strength and in vitro drug release were carried out. Theophylline encapsulation of up to 74% was achieved and drug release was monitored in SGF (pH 1.2) and SIF (pH 7.4). Results show that the matrix releases drug at a much faster rate in the basic medium than in the acidic medium, thereby holding the promise of developing the semi-IPN system as a potential candidate for the release of theophylline. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Determination of the release mechanism of Theophylline from pellets coated with Surelease®-A water dispersion of ethyl cellulose.

    Science.gov (United States)

    Kazlauske, Jurgita; Cafaro, Maria Margherita; Caccavo, Diego; Marucci, Mariagrazia; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette

    2017-08-07

    The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51μm) of the coating layer controlling the drug release rate. Copyright © 2017. Published by Elsevier B.V.

  3. Treatment plan comparison in acute and chronic respiratory tract diseases: an observational study of doxophylline vs. theophylline.

    Science.gov (United States)

    Mennini, F S; Sciattella, P; Marcellusi, A; Marcobelli, A; Russo, A; Caputi, A P

    2017-10-01

    The main objective of this article is to estimate the global cost related to the use of the two drugs (associated drugs, specialist visits, hospital admissions, plasma drug monitoring). The drug prescriptions were extracted from the Information System of the Pharmaceutical Prescriptions of the Marche Region for each ATC code in the years 2008-2012 and the number of patients per year and other outcomes measure were obtained. 13,574 patients were treated with theophylline and 19,426 patients with doxophylline. The number of patients treated was approximately 5,000 per year. Co-prescription with other drugs, use of corticosteroids, mean number of visits and hospital admissions (per 100 patients) were lower for doxophylline vs theophylline (1.55vs5.50, 0.3vs0.7, 2.05vs3.73 and 1.57vs3.3 respectively). The annual mean cost per patient was €187.4 for those treated with doxophylline and €513.5 for theophylline. In our study, doxophylline resulted to be associated with a reduction of the overall cost.

  4. The Evidence for Intravenous Theophylline Levels between 10-20mg/L in Children Suffering an Acute Exacerbation of Asthma: A Systematic Review.

    Directory of Open Access Journals (Sweden)

    Lewis Cooney

    Full Text Available Intravenous theophyllines are a second line treatment for children suffering an acute exacerbation of asthma. Various guidelines and formularies recommend aiming for serum theophylline levels between 10-20mg/l. This review aims to assess the evidence underpinning this recommendation.A systematic review comparing outcomes of children who achieved serum theophylline concentrations between 10-20mg/l with those who did not. Primary outcomes were time until resolution of symptoms, mortality and need for mechanical ventilation. Secondary outcomes were date until discharge criteria are met, actual discharge, adverse effects and FEV1.MEDLINE, CINAHL, CENTRAL and Web of Science. Search performed in October 2015.Interventional or observational studies utilizing intravenous theophyllines for an acute exacerbation of asthma in children where serum theophylline levels and clinical outcomes were measured.10 RCTs and 2 observational studies were included. Children with serum levels between 10-20mg/l did not have a reduction in duration of symptoms, length of hospital stay or need for mechanical ventilation or better spirometric results compared with levels<10mg/l. Levels above 20mg/l are not associated with higher rates of adverse effects. This study is limited due to heterogeneity in the way theophylline levels were reported and poor surveillance of adverse effects across studies.Dosing strategies aiming for levels between 10-20mg/l are not associated with better outcomes. Clinicians should rely on clinical outcomes and not serum levels when using intravenous theophyllines in children suffering an acute exacerbation of asthma.

  5. Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: studies using medium to high doses in animal models.

    Science.gov (United States)

    López-Cruz, Laura; Pardo, Marta; Salamone, John D; Correa, Mercè

    2014-08-15

    Caffeine and theophylline are methylxanthines that are broadly consumed, sometimes at high doses, and act as minor psychostimulants. Both are nonselective adenosine antagonists for A1 and A2A receptors, which are colocalized with dopamine D1 and D2 receptors in striatal areas. Adenosine antagonists generally have opposite actions to those of dopamine antagonists. Although the effects of caffeine are widely known, theophylline has been much less well characterized, especially at high doses. Adult male CD1 mice were used to study the effect of a broad range of doses (25.0, 50.0 or 100.0mg/kg) of caffeine and theophylline on measures of spontaneous locomotion and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas rich in adenosine and dopamine receptors. In addition, we evaluated possible anxiety and stress effects of these doses. Caffeine, at these doses, impaired or suppressed locomotion in several paradigms. However, theophylline was less potent than caffeine at suppressing motor parameters, and even stimulated locomotion. Both drugs induced corticosterone release, however caffeine was more efficacious at intermediate doses. While caffeine showed an anxiogenic profile at all doses, theophylline only did so at the highest dose used (50mg/kg). Only theophylline increased c-Fos immunoreactivity in cortical areas. Theophylline has fewer disruptive effects than caffeine on motor parameters and produces less stress and anxiety effects. These results are relevant for understanding the potential side effects of methylxanthines when consumed at high doses. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Analysis of Pseudo-polymorphism Conversion of Theophylline During Wet Granulation and Drying Processes and Effect of Binder on Dehydration and Amorphization

    Science.gov (United States)

    Sakamoto, Tomoaki; Sasaki, Tetsuo; Katori, Noriko; Goda, Yukihiro

    2016-10-01

    We conducted a time-course analysis of the pseudo-polymorphism conversion (i.e., the hydration and dehydration) of the xanthine-related compound theophylline during wet granulation and drying processes, using terahertz spectroscopy. We also investigated the amorphization mechanism of theophylline hydrate during a drying process in a vacuum using terahertz, mid-infrared (mid-IR), and near-infrared (near-IR) spectroscopy. After a high-shear granulation process using a mixture of theophylline, hydroxypropyl cellulose (HPC), and water, the terahertz spectrum (which was similar to that of an anhydride) was changed to a spectrum that was quite similar to that of a monohydrate. This result suggests that (1) an anhydride was converted to a monohydrate during the wet granulation process and (2) the spectrum was changed to the original waveform after the drying process with heat. This phenomenon indicates that the theophylline monohydrate was reconverted to an anhydride during the drying process. When wet granules were dried in a vacuum, the terahertz absorption lessened and finally disappeared with the passage of time, suggesting that the theophylline monohydrate in the granules was converted to an amorphous state. During the drying process with heat, the dehydration progressed temperature dependently regardless of the presence/absence of HPC. In addition, the reconversion from a monohydrate to an anhydride was completed concurrently with the completion of dehydration. The conversion rate of theophylline from a monohydrate to an amorphous form in granules (with HPC) was faster than that without HPC. This observation suggests that HPC promotes the amorphization of theophylline.

  7. The effect of theophylline on sleep-disordered breathing in patients with stable chronic congestive heart failure.

    Science.gov (United States)

    Hu, Ke; Li, Qingquan; Yang, Jiong; Hu, Suping; Chen, Xilan

    2003-11-01

    To determine the prevalence of sleep-disordered breathing in patients with stable, optimally treated chronic congestive heart failure and the effect of short-term oral theophylline therapy on periodic breathing in these patients. Patients with stable, optimally treated chronic congestive heart failure were monitored by polysomnography during nocturnal sleep. The effects of theophylline therapy on periodic breathing associated with stable heart failure were observed before and after treatment. Patients were divided into two groups. Group I (n = 21) consisted of individuals with 15 episodes of apnea and hypopnea [as determined by the apnea-hypopnea index (AHI)] per hour or less; Group II (n = 15, 41.7%) individuals had an index of more than 15 episodes per hour. In group II, the AHI varied from 16.8 to 78.8 (42.6 +/- 15.5) in which the obstructive AHI was 11.1 +/- 8.4 and the central AHI was 31.5 +/- 9.6. Group II had significantly more arousals (36.8 +/- 21.3 compared with 19.4 +/- 11.2 in group I) that were directly attributable to episodes of apnea and hypopnea, lower arterial oxyhemoglobin saturation (76.7% +/- 4.6% compared with 86.5% +/- 2.8%) and lower left ventricular ejection fraction (24.2% +/- 8.8% compared with 31.5% +/- 10.6%). Thirteen patients with compensated heart failure and periodic breathing received theophylline orally (at an average dose of 4.3 mg/kg) for five to seven days. After treatment, the mean plasma theophylline concentration was (11.3 +/- 2.5) micro g/ml. Theophylline therapy resulted in significant decreases in the number of AHI (20.8 +/- 13.2 vs. 42.6 +/- 15.5; P arterial oxyhemoglobin saturation (SaO(2)) was less than 90 percent (8.8% +/- 8.6% vs. 23.4% +/- 24.1%; P arterial oxyhemoglobin desaturation during nocturnal sleep.

  8. Efficacy of theophylline compared to methylphenidate for the treatment of attention-deficit hyperactivity disorder in children and adolescents: a pilot double-blind randomized trial.

    Science.gov (United States)

    Mohammadi, M R; Kashani, L; Akhondzadeh, S; Izadian, E S; Ohadinia, S

    2004-04-01

    Attention-deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3-6% of school children. Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative, safe and effective medications in the treatment of this disorder. Theophylline is a psychomotor stimulant most widely used as a broncodilator. Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders. We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylphenidate for the treatment of ADHD. A total of 32 children with ADHD as defined by DSM IV were randomized to theophylline and methylphenidate dosed on an age and weight-adjusted basis at 4 mg/kg/day (under 12 years) and 3 mg/kg/day theophylline (over 12 years) (group 1) and 1 mg/kg/day methylphenidate (group 2) for a 6-week double-blind and randomized clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist, at baseline and at 14, 28 and 42 days after start of the medication. No significant differences were observed between theophylline and methylphenidate on the Parent and Teacher Rating Scale scores over the trial (t = 0.49, d.f. = 24 P = 0.62 and t = 0.19, d.f. = 24 P = 0.54 respectively). Although the number of dropouts in the methylphenidate group was higher than the theophylline group, there was no significant difference between the two protocols in terms of the dropouts. In addition, headaches were observed more often in the methylphenidate group. The results suggest that theophylline may be a useful for the treatment of ADHD. In addition, a tolerable side

  9. Adenosine A1 receptor mRNA expression and the effects of systemic theophylline administration on respiratory function 4 months after C2 hemisection.

    Science.gov (United States)

    Nantwi, Kwaku D; Basura, Gregory J; Goshgarian, Harry G

    2003-01-01

    Previous studies from our laboratory have demonstrated that in an animal model of acute cervical spinal cord injury (SCI), respiratory function can be restored by theophylline. We also have shown that respiratory recovery occurs spontaneously after prolonged postinjury survival periods when a hemidiaphragm is paralyzed by an ipsilateral upper cervical (C2) spinal cord hemisection. Theophylline mediates functional recovery by central nervous system adenosine A1 receptor antagonism; however, it is unclear whether adenosine receptors are altered after prolonged postinjury periods and whether theophylline can further enhance restored respiratory function that occurs spontaneously. To assess putative effects of systemic theophylline administration on further enhancing spontaneous respiratory muscle recovery 4 months after C2 hemisection in rats and to determine whether adenosine A1 receptor mRNA expression is altered in these animals. Electrophysiologic assessment of respiratory activity in the phrenic nerves was conducted in C2 hemisected rats 4 months after hemisection under standardized conditions. Immediately thereafter, rats were killed and the cervical spinal cords were prepared for adenosine A1 receptor mRNA expression by in situ hybridization. Spontaneous recovery of respiratory activity in the ipsilateral phrenic nerve was detected in a majority (15/20) of C2 hemisected animals and amounted to 44.06% +/- 2.38% when expressed as a percentage of activity in the homolateral phrenic nerve in noninjured animals. At the optimal dosage used in the acute studies, theophylline (15 mg/kg) did not enhance, but rather unexpectedly blocked, recovered respiratory activity in 4 out of 5 animals tested. At dosages of 5 mg/kg and 2.5 mg/kg, the drug blocked recovered respiratory activity in 3 out of 4 and 3 out of 5 animals tested, respectively. Quantitative analysis of adenosine A1 receptor mRNA expression did not reveal a significant difference between experimental animals

  10. Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats.

    Science.gov (United States)

    Acuña-Lizama, Miguel M; Bata-García, José L; Alvarez-Cervera, Fernando J; Góngora-Alfaro, José L

    2013-07-01

    In order to assess whether caffeine and theophylline have the same potency and efficacy to reverse the impairment of motor function caused by acute or chronic interruption of striatal dopamine transmission, a comparison of their dose-response relationship was made in the acute model of haloperidol-induced catalepsy, and the chronic model of unilateral lesion of the dopamine nigrostriatal pathway with 6-hydroxydopamine. At equimolar doses, both drugs reduced catalepsy intensity and increased its onset latency in a dose-dependent fashion, showing comparable potencies and attaining the maximal effect at similar doses. Catalepsy intensity: caffeine ED₅₀ = 24.1 μmol/kg [95% CI, 18.4-31.5]; theophylline ED₅₀ = 22.0 μmol/kg [95% CI, 17.0-28.4]. Catalepsy latency: caffeine ED₅₀ = 27.0 μmol/kg [95% CI, 21.1-34.6]; theophylline ED₅₀ = 28.8 μmol/kg [95% CI, 22.5-36.7]. In one group of hemiparkinsonian rats (n = 5), caffeine caused a dose-dependent recovery of the contralateral forepaw stepping: ED₅₀ = 2.4 μmol/kg/day [95% CI, 1.9-3.1]), reaching its maximum at the dose of 5.15 μmol/kg/day. When the treatment of these same rats was switched to 5.15 μmol/kg/day of theophylline, the stepping recovery was only 51 ± 12% of that induced by caffeine. Assessing the dose-response relationship of theophylline in another group of hemiparkinsonian rats (n = 7) revealed that it caused stepping recovery in an all-or-none fashion. Thus, the three lower doses had no effect, but at the dose of 5.15 μmol/kg/day theophylline suddenly increased the stepping to 56 ± 5% of the maximal effect observed when the treatment of these same rats was switched to an equimolar dose of caffeine. Increasing the dose of theophylline up to 15.45 μmol/kg/day caused no further stepping improvement since it was only 41 ± 6% of the maximal effect produced by caffeine at the dose of 5.15 μmol/kg/day. Given that theophylline showed less potency and efficacy than caffeine to reverse the

  11. Lung injury after simulated cardiopulmonary bypass in an isolated perfused rat lung preparation: Role of mitogen-activated protein kinase/Akt signaling and the effects of theophylline.

    Science.gov (United States)

    Markou, Thomais; Chambers, David J

    2014-11-01

    Lung deflation and inflation during cardiac surgery with cardiopulmonary bypass contributes to pulmonary dysfunction postoperatively. Theophylline treatment for lung diseases has traditionally been thought to act by phosphodiesterase inhibition; however, increasing evidence has suggested other plausible mechanisms. We investigated the effects of deflation and reinflation on signaling pathways (p38-mitogen-activated protein kinase [MAPK], extracellular signal-regulated kinase 1 and 2 [ERK1/2], and Akt) and whether theophylline influences the deflation-induced lung injury and associated signaling. Isolated rat lungs were perfused (15 mL/min) with deoxygenated rat blood in bicarbonate buffer and ventilated. After 20 minutes' equilibration, the lungs were deflated (60 minutes, aerobic perfusion 1.5 mL/min), followed by reinflation (60 minutes, anaerobic reperfusion 15 mL/min). Compliance, vascular resistance, and kinase phosphorylation were assessed during deflation and reinflation. The effects of SB203580 (50 μM), a p38-MAPK inhibitor, and theophylline (0.083 mM [therapeutic] or 3 mM [supratherapeutic]) on physiology and signaling were studied. Deflation reduced compliance by 44% compared with continuously ventilated lungs. p38-MAPK and Akt phosphorylation increased (three to fivefold) during deflation and reinflation, and ERK1/2 phosphorylation increased (approximately twofold) during reinflation. SB203580 had no effect on lung physiology or ERK1/2 and Akt activation. Both theophylline doses increased cyclic adenosine monophosphate, but only 3 mM theophylline improved compliance. p38-MAPK phosphorylation was not affected by theophylline; 0.083 mM theophylline inhibited reinflation-induced ERK1/2 phosphorylation (72%±3%); and 3 mM theophylline inhibited Akt phosphorylation during deflation (75%±5%) and reinflation (87%±4%). Lung deflation and reinflation stimulates differential p38-MAPK, ERK1/2, and Akt activation, suggesting a role in lung injury during

  12. Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent.

    Science.gov (United States)

    Malamatari, Maria; Somavarapu, Satyanarayana; Kachrimanis, Kyriakos; Bloxham, Mark; Taylor, Kevin M G; Buckton, Graham

    2016-11-30

    Inhalable theophylline particles with various amounts of mannitol were prepared by combining wet milling in isopropanol followed by spray drying. The effect of mannitol as a co-milling agent on the micromeritic properties, solid state and aerosol performance of the engineered particles was investigated. Crystal morphology modelling and geometric lattice matching calculations were employed to gain insight into the intermolecular interactions that may influence the mechanical properties of theophylline and mannitol. The addition of mannitol facilitated the size reduction of the needle-like crystals of theophylline and also their assembly in microcomposites by forming a porous structure of mannitol nanocrystals wherein theophylline particles are embedded. The microcomposites were found to be in the same crystalline state as the starting material(s) ensuring their long-term physical stability upon storage. Incorporation of mannitol resulted in microcomposite particles with smaller size, more spherical shape and increased porosity. The aerosol performance of the microcomposites was markedly enhanced compared to the spray-dried suspension of theophylline wet milled without mannitol. Overall, wet co-milling with mannitol in an organic solvent followed by spray drying may be used as a formulation approach for producing respirable particles of water-soluble drugs or drugs that are prone to crystal transformation in an aqueous environment (i.e. formation of hydrates). Copyright © 2016. Published by Elsevier B.V.

  13. Theophylline-dependent riboswitch as a novel genetic tool for strict regulation of protein expression in Cyanobacterium Synechococcus elongatus PCC 7942.

    Science.gov (United States)

    Nakahira, Yoichi; Ogawa, Atsushi; Asano, Hiroyuki; Oyama, Tokitaka; Tozawa, Yuzuru

    2013-10-01

    The cyanobacterium Synechococcus elongatus PCC 7942 is a major model species for studies of photosynthesis. It is are also a potential cell factory for the production of renewable biofuels and valuable chemicals. We employed engineered riboswitches to control translational initiation of target genes in this cyanobacterium. A firefly luciferase reporter assay revealed that three theophylline riboswitches performed as expected in the cyanobacterium. Riboswitch-E* exhibited very low leaky expression of luciferase and superior and dose-dependent on/off regulation of protein expression by theophylline. The maximum magnitude of the induction vs. basal level was ∼190-fold. Furthermore, the induction level was responsive to a wide range of theophylline concentrations in the medium, from 0 to 2 mM, facilitating the fine-tuning of luciferase expression. We adapted this riboswitch to another gene regulation system, in which expression of the circadian clock kaiC gene product is controlled by the theophylline concentration in the culture medium. The results demonstrated that the adequately adjusted expression level of KaiC restored complete circadian rhythm in the kaiC-deficient arrhythmic mutant. This theophylline-dependent riboswitch system has potential for various applications as a useful genetic tool in cyanobacteria.

  14. A self-assembling RNA aptamer-based graphene oxide sensor for the turn-on detection of theophylline in serum.

    Science.gov (United States)

    Ling, Kai; Jiang, Hongyan; Li, Yang; Tao, Xiaojun; Qiu, Chen; Li, Fu-Rong

    2016-12-15

    To date, few effective fluorescent biosensors based on RNA aptamers have been developed because the intrinsic instability of RNA in the presence of nucleases precludes the application of RNA aptamers for the analysis of biological fluids. In this study, we developed a simple, sensitive, selective turn-on fluorescent aptasensor for theophylline detection in serum, utilizing ligand-induced self-assembling RNA aptamers and two different interaction stages of the aptamer fragments with graphene oxide (GO). A single strand of the theophylline RNA aptamer (33-mer) was split at the end loop region into two shorter fragments, one of which was labeled with a fluorophore (FAM). In the absence of theophylline, the adsorption of the two individual fragments on GO brought the fluorophore in close proximity to the GO surface, resulting in highly efficient quenching of fluorescence. The system showed very low background fluorescence. Conversely, the fragments self-assembled into an RNA aptamer/theophylline complex and were dissociated from GO. The quenched fluorescence was significantly recovered, and theophylline could be detected at a wide range of concentrations from 1 to 100μM, with a detection limit of 0.155μM and good selectivity in serum. Moreover, because of the shorter RNA fragments and the effective protection ability of GO from nuclease cleavage, the RNA sequences remained stable during the experiments. This design may serve as an example for the application of RNA aptasensors in the clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Alkaloids and athlete immune function: caffeine, theophylline, gingerol, ephedrine, and their congeners.

    Science.gov (United States)

    Senchina, David S; Hallam, Justus E; Kohut, Marian L; Nguyen, Norah A; Perera, M Ann d N

    2014-01-01

    Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.

  16. Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.

    Science.gov (United States)

    Lelo, A; Birkett, D J; Robson, R A; Miners, J O

    1986-01-01

    The pharmacokinetics of caffeine (CA), paraxanthine (PX), theobromine (TB) and theophylline (TP) were studied in six healthy male volunteers after oral administration of each compound on separate occasions. The total plasma clearances of CA and PX were similar in value (2.07 and 2.20 ml min-1 kg-1, respectively) as were those for TP and TB (0.93 and 1.20 ml min-1 kg-1, respectively). The unbound plasma clearances of CA and PX were also similar in magnitude (3.11 and 4.14 ml min-1 kg-1, respectively) as were those of TP and TB (1.61 and 1.39 ml min-1 kg-1, respectively). The half-lives of TP and TB (6.2 and 7.2 h, respectively) were significantly longer than those of CA and PX (4.1 and 3.1 h, respectively). The volume of distribution at steady state of TP (0.44 l kg-1) was lower than that of the other methylxanthines (0.63-0.72 l kg-1). The unbound volume of distribution of TP (0.77 l kg-1) was however the same as that of TB (0.79 l kg-1) whereas the unbound volume of distribution of PX (1.18 l kg-1) was similar to that of CA (1.06 l kg-1). PMID:3756065

  17. Study on the paper substrate room temperature phosphorescence of theobromine, caffeine and theophylline and analytical application

    Science.gov (United States)

    Chuan, Dong; Yan-Li, Wei; Shao-Min, Shuang

    2003-05-01

    Paper substrate room temperature phosphorescence (RTP) of theobromine (TB), caffeine (CF) and theophylline (TP) were investigated. The method is based on fast speed quantitative filter paper as substrate and KI-NaAc as heavy atom perturber. Various factors affecting their RTP were discussed in detail. Under the optimum experimental conditions, the linear dynamic range, limit of detection (LOD), and relative standard deviation (R.S.D.) were 14.41˜576.54 ng per spot, 1.14 ng per spot, 4.8% for TB, 5.44˜699.08 ng per spot, 0.78 ng per spot, 1.56% for CF, 7.21˜360.34 ng per spot, 1.80 ng per spot, 3.80% for TP, respectively. The first analytical application for the determination of these compounds was developed. The recovery of standard samples added to commercial products chocolate, tea, coffee and aminophylline is in the range 92.80-106.08%. The proposed method was successfully applied to real sample analysis without separation.

  18. The interaction of lysozyme with caffeine, theophylline and theobromine in solution.

    Science.gov (United States)

    Zhang, Hong-Mei; Tang, Bo-Ping; Wang, Yan-Qing

    2010-10-01

    The interactions of lysozyme with caffeine (Caf), theophylline (Tph) and theobromine (Tbr) were investigated using UV-Vis absorption, fluorescence, synchronous fluorescence, and three-dimensional fluorescence spectra techniques. The results revealed that Caf (Tph or Tbr) caused the fluorescence quenching of lysozyme by the formation of Caf (Tph or Tbr)-lysozyme complex. The binding constants (K(A)) and thermodynamic parameters (ΔG°, ΔH°, ΔS°) at two different temperatures, the binding locality, and the binding power were obtained. The results showed that the process of binding Caf (Tph or Tbr) to lysozyme was a spontaneous molecular interaction procedure and the hydrophobic and electrostatic interactions play a major role in stabilizing the complex; The distance r between donor (lysozyme) and acceptor (Caf, Tph or Tbr) was obtained according to fluorescence resonance energy transfer. The effect of Caf (Tph or Tbr) on the conformation of lysozyme was analyzed using synchronous fluorescence and three-dimensional fluorescence spectra techniques. The results showed that the binding of Caf (Tph or Tbr) to lysozyme induced some micro-environmental and conformational changes in lysozyme and disturbed the environment of the polypeptide of lysozyme.

  19. Different antibacterial activity of novel theophylline-based ionic liquids - Growth kinetic and cytotoxicity studies.

    Science.gov (United States)

    Borkowski, Andrzej; Ławniczak, Łukasz; Cłapa, Tomasz; Narożna, Dorota; Selwet, Marek; Pęziak, Daria; Markiewicz, Bartosz; Chrzanowski, Łukasz

    2016-08-01

    The aim of this study was to investigate novel theophylline-based ionic liquids and their cytotoxic effects towards model Gram-positive and Gram-negative bacteria (Bacillus cereus and Escherichia coli, respectively). Growth kinetics, respiratory rates and dehydrogenase activities were studied in the presence of ionic liquids at concentrations ranging from 10 to 1000mg/L. Additionally, the influence of ionic liquids on bacterial cells associated with specific interactions based on the structure of cell wall was evaluated. This effect was assessed by viability tests and scanning electron microscope observations. The obtained results confirmed that ionic liquids exhibit different levels of toxicity in relation to Gram-positive and Gram-negative bacteria. Those effects are associated with the chemical structure of the cationic species of the ionic liquids and their critical micelle concentration value. It was established that the presence of an alkyl or allyl group increased the toxicity, whereas the presence of an aryl group in the cation decreased the toxic effect of ILs. Results presented in this study also revealed unexpected effects of self-aggregation of E. coli cells. Overall, it was established that the studied ILs exhibited higher toxicity towards Gram-positive bacteria due to different interactions between the ILs and the cell membranes. These findings may be of importance for the design of ILs with targeted antimicrobial properties. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Regulation of Gene Expression in Diverse Cyanobacterial Species by Using Theophylline-Responsive Riboswitches

    Science.gov (United States)

    Ma, Amy T.; Schmidt, Calvin M.

    2014-01-01

    Cyanobacteria are photosynthetic bacteria that are currently being developed as biological production platforms. They derive energy from light and carbon from atmospheric carbon dioxide, and some species can fix atmospheric nitrogen. One advantage of developing cyanobacteria for renewable production of biofuels and other biological products is that they are amenable to genetic manipulation, facilitating bioengineering and synthetic biology. To expand the currently available genetic toolkit, we have demonstrated the utility of synthetic theophylline-responsive riboswitches for effective regulation of gene expression in four diverse species of cyanobacteria, including two recent isolates. We evaluated a set of six riboswitches driving the expression of a yellow fluorescent protein reporter in Synechococcus elongatus PCC 7942, Leptolyngbya sp. strain BL0902, Anabaena sp. strain PCC 7120, and Synechocystis sp. strain WHSyn. We demonstrated that riboswitches can offer regulation of gene expression superior to that of the commonly used isopropyl-β-d-thiogalactopyranoside induction of a lacIq-Ptrc promoter system. We also showed that expression of the toxic protein SacB can be effectively regulated, demonstrating utility for riboswitch regulation of proteins that are detrimental to biomass accumulation. Taken together, the results of this work demonstrate the utility and ease of use of riboswitches in the context of genetic engineering and synthetic biology in diverse cyanobacteria, which will facilitate the development of algal biotechnology. PMID:25149516

  1. Molecularly imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) modified glassy carbon electrode as an electrochemical theophylline sensor

    Energy Technology Data Exchange (ETDEWEB)

    Aswini, K.K., E-mail: aswinikk@ymail.com; Vinu Mohan, A.M.; Biju, V.M., E-mail: vmbiju@ymail.com

    2016-08-01

    Theophylline is an inexpensive drug employed in asthma and chronic obstructive pulmonary disorder medications and is toxic at higher concentration. The development of a molecularly imprinted polymer based theophylline electrochemical sensor on glassy carbon electrode by the electropolymerization of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid is being discussed in this work. The MIP modification enhances the theophylline recognition ability and the electron transfer kinetics of the bare electrode. The parameters, controlling the performance of the imprinted polymer based sensor, like number of electropolymerization cycles, composition of the pre-polymerization mixture, pH and immersion time were investigated and optimized. The interaction energy and the most stable conformation of the template–monomer complex in the pre-polymerization mixture were determined computationally using ab initio calculations based on density functional theory. The amperometric measurements showed that the developed sensor has a method detection limit of 0.32 μM for the dynamic range of 0.4 to 17 μM, at optimized conditions. The transducer possesses appreciable selectivity in the presence of structurally similar interferents such as theobromine, caffeine and doxofylline. The developed sensor showed remarkable stability and reproducibility and was also successfully employed in theophylline detection from commercially available tablets. - Highlights: • Molecularly imprinted polymer based theophylline sensor was developed. • Imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) was electrodeposited. • Most stable template-monomer complex was assigned by computational analysis. • Possessed remarkable selectivity in the presence of structurally similar interferents • Employed for theophylline detection from commercially available tablets.

  2. Preparation of hybrid molecularly imprinted polymer with double-templates for rapid simultaneous purification of theophylline and chlorogenic acid in green tea.

    Science.gov (United States)

    Tang, Weiyang; Li, Guizhen; Row, Kyung Ho; Zhu, Tao

    2016-05-15

    A novel double-templates technique was adopted for solid-phase extraction packing agent, and the obtained hybrid molecularly imprinted polymers with double-templates (theophylline and chlorogenic acid) were characterized by fourier transform infrared and field emission scanning electron microscope. The molecular recognition ability and binding capability for theophylline and chlorogenic acid of polymers was evaluated by static absorption and dynamic adsorption curves. A rapid and accurate approach was established for simultaneous purification of theophylline and chlorogenic acid in green tea by coupling hybrid molecularly imprinted solid-phase extraction with high performance liquid chromatography. With optimization of SPE procedure, a reliable analytical method was developed for highly recognition towards theophylline and chlorogenic acid in green tea with satisfactory extraction recoveries (theophylline: 96.7% and chlorogenic acid: 95.8%). The limit of detection and limit of quantity of the method were 0.01 μg/mL and 0.03 μg/mL for theophylline, 0.05 μg/mL and 0.17 μg/mL for chlorogenic acid, respectively. The recoveries of proposed method at three spiked levels analysis were 98.7-100.8% and 98.3-100.2%, respectively, with the relative standard deviation less than 1.9%. Hybrid molecularly imprinted polymers with double-templates showed good performance for two kinds of targets, and the proposed approach with high affinity of hybrid molecularly imprinted polymers might offer a novel method for the purification of complex samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. N-acetylcysteine instead of theophylline in patients with COPD who are candidates for elective off-pump CABG surgery: Is it possible in cardiovascular surgery unit?

    Directory of Open Access Journals (Sweden)

    Seyed Jalil Mirhosseini

    2013-01-01

    Full Text Available Background: Forced expiratory volume in one second (FEV1 is a good predictor of chronic obstructive pulmonary disease (COPD. COPD is characterized by a chronic limitation of airflow. This study was designed to compare the effects and complications of theophylline alone, N-acetylcysteine (NAC alone, and a combination of the two drugs on the rates of FEV1 in patients with COPD who were candidates for off-pump coronary artery bypass graft (CABG surgery. Methods: This clinical trial was performed on 100 patients who had a smoking history of 27 pack years with a range of 20 to 40 pack years but were not heavy smokers and were candidates for elective off-pump CABG surgery in Afshar Cardiovascular Hospital, Yazd, Iran. The patients with a history of asthma and bronchospasm and non-COPD respiratory disorders were excluded. There were three groups, that is, the theophylline group (n=33 that received theophylline 10 mg/kg TDS after consumption of food, NAC group (n=33 who received NAC 10-15 mg/kg BD after consumption of food, and the combined group (n=32 who received theophylline and NAC together. Data were analyzed by analysis of variance (ANOVA, Chi-square, and exact test for quantitative and qualitative variables. Results: One hundred patients with COPD enrolled in this study as possible candidates for CABG surgery. Average age of the patients was 60.36±10.21 years. Of the participants, 83 (83.3% were male and 17 (17% were female. Rate of postoperative FEV1 to basal FEV1 was 0.76±0.32, 0.66±0.22, and 0.69±0.24 in the treatments with theophylline, NAC, and the combination, respectively. Theophylline, NAC, and a combination of these drugs can decrease the rate of postoperative FEV1 compared to basal FEV1 significantly. (P=0.0001 Conclusion: Theophylline alone, NAC alone, and a combination of these drugs improve pulmonary function, and there are no significant differences between these protocols. Stomach discomfort and cardiac complications in

  4. Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Devereux, Graham; Cotton, Seonaidh; Barnes, Peter; Briggs, Andrew; Burns, Graham; Chaudhuri, Rekha; Chrystyn, Henry; Davies, Lisa; De Soyza, Anthony; Fielding, Shona; Gompertz, Simon; Haughney, John; Lee, Amanda J; McCormack, Kirsty; McPherson, Gladys; Morice, Alyn; Norrie, John; Sullivan, Anita; Wilson, Andrew; Price, David

    2015-06-10

    Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring

  5. Comprehensive characterization of a theophylline riboswitch reveals two pivotal features of Shine-Dalgarno influencing activated translation property.

    Science.gov (United States)

    Cui, Wenjing; Cheng, Jintao; Miao, Shengnan; Zhou, Li; Liu, Zhongmei; Guo, Junling; Zhou, Zhemin

    2017-03-01

    Tuneable gene expression controlled by synthetic biological elements is of great importance to biotechnology and synthetic biology. The synthetic riboswitch is a pivotal type of elements that can easily control the heterologous gene expression in diverse bacteria. In this study, the theophylline-dependent synthetic riboswitch and the corresponding variants with varied spacings between Shine-Dalgarno (SD) sequence and start codon were employed to comprehensively characterize the induction and regulation properties through combining a strong promoter aprE in Bacillus subtilis. Amongst the sets of newly constructed expression elements, the expression element with 9-bp spacing exhibited the higher expression level, a superior induction fold performance, and a considerably lower leaky expression than those with longer or shorter spacings. The riboswitch expression element with 9-bp spacing showed an approximately linear dose dependence from 0 to 8 mM of theophylline. Modification of the SD sequence through the insertion of a single A base prior to the native sequence enables the increase of the expression level post induction while decreasing the induction fold as a result of the elevated leaky level. The riboswitch elements with the engineered SD and the optimal 9-bp spacing exhibit an altered dose dependency in which the approximately linear range shifts to 0-4 mM, although it has a similar profile to the induction process. These results not only provide comprehensive data for the induced expression by a theophylline riboswitch combined with a strong native promoter from B. subtilis but also provide the two pivotal features of SD essential to the modular design of other synthetic riboswitches.

  6. Effects of long-term theophylline exposure on recovery of respiratory function and expression of adenosine A1 mRNA in cervical spinal cord hemisected adult rats.

    Science.gov (United States)

    Nantwi, Kwaku D; Basura, Gregory J; Goshgarian, Harry G

    2003-07-01

    Our lab has previously shown that when administered acutely, the methylxanthine theophylline can activate a latent respiratory motor pathway to restore function to the hemidiaphragm paralyzed by an ipsilateral C2 spinal cord hemisection. The recovery is mediated by the antagonism of CNS adenosine A1 receptors. The objective of the present study was to assess quantitatively recovery after chronic theophylline administration, the effects of weaning from the drug, and the effects of the drug on adenosine A1 receptor mRNA expression in adult rats subjected to a C2 hemisection. Rats subjected to a left C2 hemisection received theophylline orally for 3, 7, 12, or 30 days and were classified as 3D, 7D, 12D, or 30D respectively. Separate groups of 3D animals were weaned from drug administration for 7, 12, and 30 days before assessment of respiratory recovery. Additional groups of 7D and 12D animals were also weaned from drug administration for 7 and 12 days prior to assessment. Sham-operated controls received theophylline vehicle for similar periods. Quantitative assessment of recovered respiratory activity was conducted under standardized electrophysiologic recording conditions approximately 18 h after each drug application period. Serum theophylline analysis was conducted at the end of electrophysiologic recordings. Adenosine A1 receptor mRNA expression in the phrenic nucleus was assessed with in situ hybridization and immunohistochemistry. Chronic theophylline induced a dose-dependent effect on respiratory recovery over a serum theophylline range of 1.2-1.9 microg/ml. Recovery was characterized as respiratory-related activity in the left phrenic nerve and expressed as a percentage of activity in the homolateral nerve in noninjured animals under similar recording conditions. Recovered activity was 34.13 +/- 2.07, 55.89 +/- 2.96, 74.78 +/- 1.93, and 79.12 +/- 1.75% respectively in the 3D, 7D, 12D, and 30D groups. Theophylline-induced recovered activity persisted for as

  7. Synthesis of the row of new functional derivatives of 7-arylalkyl-8-hydrazine theophyllines

    Directory of Open Access Journals (Sweden)

    Dmytro Korobko

    2016-03-01

    Full Text Available Hydrazine functional derivatives are widely used in medical practice as remedies applied for pharmacotherapy of depression, infection diseases, hypertension, diabetes, etc. It is worth mentioning that among obtained 7-R-8-hydrazine derivatives of 1,3-dimethylxantine promising substances have been identified. Due to the fact that literature sources display only results of occasional studies of the reactions between 7-R-8-hydrazine theophyllines and mono- or dicarbonyle substances, the use of other keto reagents for xanthine bicycle at 8th position functionalization will allow to explore synthetic potential of the last one, and with high probability may lead to obtaining original biologically active substances.Aim. To study types of reaction between 8-hydrazinyl-1,3-dimethyl-7-aryl alkyl-1H-purine-2,6(3H,7H-diones and a number of carbonyl containing reagents.Methods. A nucleophilic addition reaction followed by dehydration or ethanol splitting was used, as well as the complex of the modern analysis methods to confirm the structure and individuality of the synthesized substances.Results. Different directions of 8-hydrazinyl-1,3,-dimethyl-7(fenetyl-, 3-phenylpropyl-, 3-phenylalyl-1H-purine-2,6(3H,7H-diones chemical transformations in reactions with the appropriate carbonyl containing compounds have been studied experimentally. The structure of synthesized substances was confirmed by chromatography/mass and 1H NMR spectroscopy.Conclusion. The group of 7-arylalkyl-8-(3,5-R,R1-pyrazole-1-yltheophyllines, consisting of two functionally substituted bioactive heterocycles, has been synthesized by reaction between initial substances and selected mono- and dicarbonyl compounds

  8. In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia Cupana.

    Science.gov (United States)

    Heard, Charles M; Johnson, Sarah; Moss, Gary; Thomas, Chris P

    2006-07-06

    Extracts of guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. The objective of this work was to investigate in vitro the transdermal delivery of the major pharmacologically active compounds contained in guarana extract. Saturated solutions of guarana were prepared in polyethylene glycol 400 (PEG400), propylene glycol (PG) and H(2)O at 32 degrees C. Guarana extract was also formulated in Duro-tak 2287 transdermal adhesive in a range of concentrations and the diffusional release was determined in addition to adhesive properties. Transdermal delivery across full thickness pig ear skin was investigated in vitro using Franz-type diffusion cells, with reverse-phase HPLC being used for the quantification of the permeation of theobromine (TB), theophylline (TP), (+)-catechin (C) and caffeine (CF). Based upon a combination of release and adhesive property data a patch containing 5.55 mg guarana extract cm(-2) was deemed optimal. The general trend for the delivery of the 4 analytes was: water >5.55 mg cm(-2) patch approximately PG>PEG400. For CF the greatest steady state flux was obtained from the water vehicle: 19 microg cm(-2)h(-1), with approximately 420 microg cm(-2) permeating after 24h. This was some 6x times more than from the drug-in-adhesive patch and 10x greater than PG, a well-known penetration enhancer, and 50x that of the 'regular' excipient PEG400. A water vehicle also provided the greatest delivery of TB (0.45 microg cm(-2) h(-1)), TP (0.022 microg cm(-2) h(-1)), and C (0.10 microg cm(-2) h(-1)). An inverse relationship was noted between lipophilicity and k(p) in each vehicle. The simultaneous transdermal delivery of the major actives of guarana was established, with permeation rates being highly concentration and vehicle dependent.

  9. The formulation of a pressurized metered dose inhaler containing theophylline for inhalation.

    Science.gov (United States)

    Zhu, Bing; Haghi, Mehra; Goud, Mary; Young, Paul M; Traini, Daniela

    2015-08-30

    Theophylline (TP) is a bronchodilator used orally to treat chronic obstructive pulmonary disease (COPD) that has been associated with multiple side effects, tempering its present use. This study aims to improve COPD treatment by creating a low-dose pressurized metered dose inhaler (pMDI) inhalable formulation of TP. Aerosol performance was assessed using Andersen Cascade Impaction (ACI). Solubility of TP in HFA 134/ethanol mixture was measured and morphology of the particles analyzed with a scanning electron microscope (SEM). Calu-3 cell viability, epithelial cell transport and inflammatory-response assays were conducted to study the impact of the formulation on lung epithelial cells. The mass deposition profile of the formulation showed an emitted dose of 250.04±14.48μg per 5 actuations, achieving the designed nominal dose (50μg/dose). SEM showed that the emitted particles were hollow with spherical morphology. Approximately 98% of TP was transported across Calu-3 epithelial cells and the concentration of interleukin-8 secreted from Calu-3 cells following stimulation with tissue necrosis factor-α (TNF-α) resulted in significantly lower level of interleukin-8 released from the cells pre-treated with TP (1.92±0.77ng·ml(-1) TP treated vs. 8.83±2.05ng·ml(-1) TNF-α stimulated, respectively). The solution pMDI formulation of TP developed in present study was shown to be suitable for inhalation and demonstrated anti-inflammatory effects at low doses in Calu-3 cell model. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Stability-indicating RP-HPLC method for simultaneous estimation of levosalbutamol sulfate and theophylline in combined dosage form

    Directory of Open Access Journals (Sweden)

    Sagar Suman Panda

    2013-09-01

    Full Text Available A novel, simple, accurate and precise RP-HPLC method for simultaneous determination of levosalbutamol sulfate and theophylline has been developed and validated. Separation was achieved on a Phenomenex; C18 column (250 mm × 4.6 mm i.d., 5 µm using methanol: 10 mM TBAHS(tetrabutyl ammonium hydrogen sulfate (50:50, v/v as mobile phase at flow rate of 1.0 mL.min-1. The UV detection wavelength was 274 nm. The linearity is obeyed over a concentration range of 0.5-150 µg.mL-1 with correlation coefficient of 0.999 for both the drugs. The proposed method was validated by determining accuracy, precision, stability and system suitability parameters. The method was found to be robust. Specificity of the method was determined by subjecting the drugs to various stress conditions like acid, alkali, oxidation, thermal and photolytic degradation. The method was used successfully for the simultaneous determination of levosalbutamol sulfate and theophylline in syrup dosage form.

  11. Hypoxia-specific inhibition of recovery from radiation damage by a novel 2-nitroimidazole with a theophylline side chain

    Energy Technology Data Exchange (ETDEWEB)

    Hodgkiss, R.J.; Kelleher, E. (Mount Vernon Hospital, Northwood (United Kingdom). Gray Lab.); Parrick, J. (Brunel Univ., Uxbridge (United Kingdom). Dept. of Chemistry)

    1992-06-01

    A novel 2-nitroimidazole with a theophylline sidechain, 7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline, (NITP) was as efficient a hypoxic-cell radiosensitizer as misonidazole. If cells were irradiated with NITP under hypoxic conditions and then exposed to the drug under aerobic conditions, a much larger radiosensitizing effect was observed, partly because of a reduction in the size of the shoulder of the survival curve. There was little effect of NITP on the radiosensitivity of well oxygenated cells, even with post-irradiation drug contact. Split-dose survival curves showed the drug inhibited recovery from radiation damage only when cells were irradiated under hypoxia but not when irradiations were under oxic conditions. A reduction in the size of the survival curve shoulder should allow the hypoxic-cell radiosensitizing efficiency of NITP to be maintained with low doses of radiation used in multifraction cancer radiotherapy. Bifunctional drugs containing both electron-affinic and repair inhibiting groups may represent a new approach to the synthesis of hypoxic-cell targeted adjuncts to radiotherapy. (Author).

  12. Comparative study of the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Lal, Dushyant; Manocha, Sachin; Ray, Arunabha; Vijayan, V K; Kumar, Raj

    2015-09-01

    Bronchial asthma and chronic obstructive pulmonary disease (COPD) are the major obstructive disorders that may contribute to the severity in individual patients. The present study was designed to compare the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and COPD. A total of 60 patients, 30 each with bronchial asthma and COPD, were enrolled for the study. Each group of 30 patients received standard treatment for asthma and COPD. Each group was again subdivided into two with 15 patients each, who received theophylline or doxofylline in addition to standard therapy, for a period of 2 months. Each patient was followed up fortnightly for the assessment of efficacy parameters using a pulmonary function test (PFT), clinical symptoms and emergency drug use, and safety was assessed by recording adverse drug reactions. Both theophylline and doxofylline produced enhancements in PFT at different time intervals in both asthma and COPD patients. The maximum beneficial effects were seen at 6 weeks for asthma patients and at 8 weeks for COPD patients for both theophylline and doxofylline. The comparative study showed that doxofylline was more effective as evidenced by improvement in PFT as well as clinical symptoms, and reduced incidence of adverse effects and emergency bronchodilator use.

  13. THE EFFECT OF THEOPHYLLINE AND IMMOBILIZATION STRESS ON HALOPERIDOL-INDUCED CATALEPSY AND ON METABOLISM IN THE STRIATUM AND HIPPOCAMPUS, STUDIED WITH LACTOGRAPHY

    NARCIS (Netherlands)

    DIJK, S; KRUGERS, HJ; KORF, J

    Whether inducing catalepsy in the rat by an intraperitoneal injection of haloperidol (0.5 mg/kg) had an effect on metabolism in the striatum and in the hippocampus, as determined by lactography, and whether reducing the cataleptic state with stress or theophylline (8 mg/kg i.v.) had any impact on

  14. Effect of pH, buffer concentration and buffer composition on the absorption of theophylline from the small intestine of the rat

    NARCIS (Netherlands)

    Blaey, C.J. de; Schurgers, N.

    1984-01-01

    The absorption of theophylline from the small intestine of the rat was investigated using buffer solutions of different pH (3.0–9.2), composition and concentration. The technique used, encloses luminal perfusion of an intestinal loop with collection of the blood draining the perfused loop, which

  15. Molecularly imprinted poly(4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid) modified glassy carbon electrode as an electrochemical theophylline sensor.

    Science.gov (United States)

    Aswini, K K; Vinu Mohan, A M; Biju, V M

    2016-08-01

    Theophylline is an inexpensive drug employed in asthma and chronic obstructive pulmonary disorder medications and is toxic at higher concentration. The development of a molecularly imprinted polymer based theophylline electrochemical sensor on glassy carbon electrode by the electropolymerization of 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid is being discussed in this work. The MIP modification enhances the theophylline recognition ability and the electron transfer kinetics of the bare electrode. The parameters, controlling the performance of the imprinted polymer based sensor, like number of electropolymerization cycles, composition of the pre-polymerization mixture, pH and immersion time were investigated and optimized. The interaction energy and the most stable conformation of the template-monomer complex in the pre-polymerization mixture were determined computationally using ab initio calculations based on density functional theory. The amperometric measurements showed that the developed sensor has a method detection limit of 0.32μM for the dynamic range of 0.4 to 17μM, at optimized conditions. The transducer possesses appreciable selectivity in the presence of structurally similar interferents such as theobromine, caffeine and doxofylline. The developed sensor showed remarkable stability and reproducibility and was also successfully employed in theophylline detection from commercially available tablets. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Low Dose Theophylline Showed an Inhibitory Effect on the Production of IL-6 and IL-8 in Primary Lung Fibroblast from Patients with COPD

    Science.gov (United States)

    Zhang, Jing; Feng, Ming-xiang; Qu, Jie-ming

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by the abnormal and chronic lung inflammation. We hypothesized that lung fibroblasts could contribute to the local inflammation and investigated whether low dose theophylline had a beneficial effect on fibroblasts inflammation. Subjects undergoing lobectomy for bronchial carcinoma were enrolled and divided into COPD and control groups according to spirometry. Primary human lung fibroblasts were cultured from peripheral lung tissue distant to tumor tissue. There was a significant increase in both the mRNA expressions and protein levels for IL-6 and IL-8 in fibroblasts in COPD group, and the values were negatively correlated with lung function (P theophylline treatment. In addition, theophylline at the dose of 5 μg/mL reduced the increased production of IL-6 and IL-8 induced by 1 μg/mL LPS in primary human lung fibroblasts. Our data suggest that lung fibroblasts participate in the chronic inflammation in COPD by releasing IL-6 and IL-8, and low dose theophylline can alleviate the proinflammatory mediators' production by fibroblasts. PMID:22363103

  17. Changes in the Biochemical Profiles of Mid-Cervically Located Adenosine A1 Receptors After Repeated Theophylline Administration in Adult Rats

    Science.gov (United States)

    Saharan, Rubabe S; Nantwi, Kwaku D

    2006-01-01

    Background/Objective: Adenosine A1 receptors localized in the phrenic motoneurons (PMNs), where the axons of the descending bulbospinal respiratory make synaptic contacts, may be involved in theophylline-induced respiratory-related activity in rats. The objective of this study was to characterize the biochemical profiles of adenosine A1 receptors in 2 groups of rats: (a) naïve and (b) theophylline-treated (3-day oral administration). Methods: Biochemical binding characteristics of adenosine A1 receptors in the C3 to C5 (PMN) of adult rats were assessed in naïve (n =6) and theophylline-treated animals (n =6) using [3H]-DPCPX (10 pmol/L to 30 nmol/L), the specific adenosine A1 receptor antagonist in saturation-binding assays. Competition assays used theophylline as the competing ligand (20 mmol/L to 20 pmol/L), and protein concentration was determined with the Bradford assay using a range of standards (0.016–1.0 mg/mL). Results: In saturation-binding assays in naïve animals, the A1 receptor was characterized by a single binding site with Bmax and Kd values of 256.00 ± 32.13 fmol/mg protein and 2.89 ± 0.45 nmol/L, respectively. Analysis of the isotherm in theophylline-treated animals showed 1 site with Bmax and Kd values of 219.00 ± 26.3 fmol/mg protein and 0.60 ± 0.21 nmol/L, respectively, and a second site characterized by Bmax and Kd values of 492.6 ± 3.15 fmol/mg protein and 14.09 ± 2.06 n mol/L, respectively. Conclusions: Theophylline administration revealed 2 binding sites on receptors (characterized by the specific adenosine A1 antagonist, [3H]-DPCPX) located in the vicinity of phrenic motoneurons (C3–C5). Alteration of the receptor profiles after theophylline may underlie the respiratory-related actions of the drug. PMID:17274491

  18. Oral Low-dose Theophylline on Top of Inhaled Fluticasone-Salmeterol Does Not Reduce Exacerbations in Patients With Severe COPD: A Pilot Clinical Trial.

    Science.gov (United States)

    Cosío, Borja G; Shafiek, Hanaa; Iglesias, Amanda; Yanez, Aina; Córdova, Rocío; Palou, Alexandre; Rodriguez-Roisin, Robert; Peces-Barba, Germán; Pascual, Sergi; Gea, Joaquim; Sibila, Oriol; Barnes, Peter J; Agusti, Alvar

    2016-07-01

    COPD is characterized by chronic inflammation. In vitro and ex vivo observations suggest that this inflammatory response is partially resistant to the effect of corticosteroids and that low-dose theophylline can restore this response via enhancement of histone deacetylase (HDAC) activity. Whether this occurs in vivo and what its potential clinical consequences are is unclear. The objective of this trial was to determine whether low-dose theophylline on top of inhaled long-acting β2-agonists and inhaled corticosteroids (ICS) in patients with COPD (1) enhances HDAC activity and the antiinflammatory effects of ICS in vivo, (2) reduces the concentration of inflammatory markers, and (3) reduces exacerbation frequency. In this prospective, double-blind, placebo-controlled clinical trial, we randomized patients with COPD (FEV1 theophylline 100 mg bid or matched placebo. We determined the following at baseline and at the end of 52 weeks of follow-up: (1) HDAC activity in blood monocytes and sputum macrophages, (2) the concentration of several inflammatory markers (IL-8, IL-6, IL-1β, and tumor necrosis factor -α) in serum and sputum supernatant, and (3) the rates of exacerbations and adverse effects. Seventy patients were randomized-36 to theophylline and 34 to placebo. HDAC activity and inflammatory marker levels were not different in the two arms either at baseline or after 52 weeks. Likewise, the rate of exacerbations during follow-up was similar in both groups. The combination of low-dose oral theophylline and ICS did not enhance the antiinflammatory properties of ICS in vivo or influence exacerbation rate. ClinicalTrials.gov; No.: NCT01599871; URL: www.clinicaltrials.gov. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations.

    Science.gov (United States)

    Machnik, Marc; Kaiser, Simone; Koppe, Sophie; Kietzmann, Manfred; Schenk, Ina; Düe, Michael; Thevis, Mario; Schänzer, Wilhelm; Toutain, Pierre-Louis

    2017-09-01

    Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2 µg/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3 µg/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations for reporting caffeine and theophylline are still lacking. The aim of the study was to investigate IRLs for theobromine in blood and for caffeine and theophylline in blood and urine. Therefore, a set of six administrations were carried out including both single i.v. and single oral administrations of caffeine, theobromine and theophylline. Plasma and urine concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Applying the Toutain model approach an effective plasma concentration (EPC) of caffeine was estimated at 3.05 µg/mL, irrelevant concentrations in blood (IPC) and urine (IUC) approached 6 and 12 ng/mL, respectively. EPC of theobromine was calculated with 3.80 µg/mL, and irrelevant concentrations of theobromine were determined at 8 ng/mL in plasma and at 142 ng/mL in urine. Toutain modelling of the theophylline data produced an EPC, IPC, and IUC of 3.20 µg/mL, 6 ng/mL, and 75 ng/mL, respectively. The obtained irrelevant concentrations were used to postulate IRLs for theobromine in plasma and for caffeine and theophylline in plasma and urine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents.

    Science.gov (United States)

    Mangasuli, Sumitra N; Hosamani, Kallappa M; Devarajegowda, Hirihalli C; Kurjogi, Mahantesh M; Joshi, Shrinivas D

    2018-02-25

    A series of novel coumarin-theophylline hybrids were synthesized and examined for their anti-tubercular activity in vitro against Mycobacterium tuberculosis H 37 Rv, anti-microbial activity in vitro against gram-positive bacteria (Staphylococcus aureus) and gram-negative bacterias (Escherichia coli, Salmonella typhi) as well as fungi (Candida albicans). The compound (3a) has shown excellent anti-tubercular activity with MIC of 0.12 μg/mL. Electron donating compounds (3a, 3f) have displayed significant anti-microbial activity. The compounds have also been precisely elucidated using single crystal X-ray diffraction techniques. Molecular docking study has been performed against 4DQU enzyme of Mycobacterium tuberculosis showed good binding interactions and is in agreement with the in vitro results. Copyright © 2018. Published by Elsevier Masson SAS.

  1. Novel extraction and application of okra gum as a film coating agent using theophylline as a model drug

    Directory of Open Access Journals (Sweden)

    Ikoni J. Ogaji

    2014-01-01

    Full Text Available The purpose of this study was to investigate the effect of extraction and application of okra gum as an aqueous film coating agent. Powdered okra pods dispersed in demineralized water was heated at 80 ± 2 o C for 30 minutes in the presence of sodium chloride. The filtrate was successively centrifuged at 4000 rpm for 30, 60, or 120 minutes and freeze dried. The samples were used as film former at different concentrations in aqueous film coating operations. Near infrared (nIR absorption spectra, photomicrographs, and some physicochemical properties of the coated tablets were evaluated. The okra gum samples had different nIR spectra and possessed good processing and application quality due to relatively low viscosity. A six-fold concentration of this gum from the novel extraction yielded glossy theophylline tablets within a short time. A t (18 = 2.895, P < 0.005, t critical = 1.734 were obtained for the independent analysis of the hardness of core and coated theophylline tablets. A 3.0% concentration of the okra samples at a flow rate of 3 ml/min for 100 minutes showed that F = 3.798, DF = 29, P < 0.035, F critical = 3.354 in tablet hardness among samples and F = 15.632, DF = 29, P < 0.0001, F critical = 2.152 were obtained on film thickness among tablet samples during the coating and drying operation. Novel extraction process enhanced the film coating potential of okra gum by delivering more solids on the substrate at a shorter time with improved operation efficiency.

  2. Effect of Variation in Viscosity Grade of Ethycellulose on Theophylline Microcapsule Properties Prepared by Emulsion Solvent Evaporation.

    Science.gov (United States)

    Garekani, Hadi Afrasiabi; Ahmadi, Behzad; Sadeghi, Fatemeh

    2017-01-01

    There are conflicting reports regarding the effect of polymer viscosity grade on microcapsule properties. The aim of the present study was to investigate the effect of just viscosity grade of ethylcellulose (EC) (not polymeric solution) on properties of theophylline microcapsules prepared by emulsion solvent evaporation. The effect of EC viscosity grade and drug:polymer ratio was investigated on microcapsule properties (yield, particle size, morphology, surface characteristics and drug release). Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) were implemented to study the interaction and solid state of drug. The microcapsules were compressed in the presence of excipients and drug release was evaluated. The yield of microencapsulation and encapsulation efficiency at 1:1 drug:polymer ratio was dependent on EC viscosity. Microcapsules were spherical with some pores on their surfaces. The number of pores was more and their size was bigger for EC 100 cP microcapsules. Theophylline remained in crystalline form after encapsulation. DSC studies confirmed lack of interaction between drug and polymer. The drug release was rapid at 2:1 drug:polymer whilst it was slowed down at 1:1 drug:polymer ratio. Microcapsules obtained from EC 100 cP showed slightly faster drug release at latter ratio. Marginal changes in release rate were observed after compression of microcapsules. All viscosity grades of EC were able to sustain the release of the drug from microcapsules. Considering the similar release profiles for microcapsules prepared from different viscosities of EC, the use of lower viscosity grade of EC is recommended due to the ease of production and also less processing time. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Evaluation of ethylcellulose and its pseudolatex (Surelease in preparation of matrix pellets of theophylline using extrusion-spheronization

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    Hadi Afrasiabi Garekani

    2017-01-01

    Full Text Available Objective(s: This study evaluates the effect of substitution of microcrystalline cellulose (MCC with ethylcellulose (EC on mechanical and release characteristics of theophylline pellets. Materials and Methods: The effect of addition of EC was investigated on characteristics of pellets with varying drug content prepared by extrusion-spheronization. Also the effect of type of granulating liquid (water or Surelease was investigated on characteristics of selected pellets. The pellets were characterized for particle size (sieve analysis, mechanical strength, morphology (microscopy, thermal (DSC and dissolution behaviors. Results: The exrtudability of the wet mass was reduced upon inclusion of EC so that complete replacement of MCC was not possible. Increase in EC percentage led to lower production yield and formation of pellets with larger diameter and slightly rough surfaces. Inclusion of EC also affected the mechanical properties of pellets but had negligible effect on drug release profile. The surface of selected pellets became smoother and their production yield increased upon the use of Surelease as granulating liquid. In addition the rate of drug release decreased to some extent when Surelease was used. Conclusion: Preparation of theophylline pellets with EC alone was not possible in process of extrusion-spheronization. Partial replacement of MCC with EC changed physicomechanical properties of pellets but hardly affected drug release. Although the use of Surelease as granulation liquid slightly decreased the rate of drug release, desirable matrix pellets with sustained drug release could not be produced. Despite this outcome however, these pellets could benefit from reduced coating thickness for drug release control.

  4. Spectroscopic-Based Chemometric Models for Quantifying Low Levels of Solid-State Transitions in Extended Release Theophylline Formulations.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval A; Khan, Mansoor A

    2016-01-01

    Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q(2) were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products. Copyright © 2016. Published by Elsevier Inc.

  5. Theophylline-assisted, eco-friendly synthesis of PtAu nanospheres at reduced graphene oxide with enhanced catalytic activity towards Cr(VI) reduction.

    Science.gov (United States)

    Hu, Ling-Ya; Chen, Li-Xian; Liu, Meng-Ting; Wang, Ai-Jun; Wu, Lan-Ju; Feng, Jiu-Ju

    2017-05-01

    Theophylline as a naturally alkaloid is commonly employed to treat asthma and chronic obstructive pulmonary disorder. Herein, a facile theophylline-assisted green approach was firstly developed for synthesis of PtAu nanospheres/reduced graphene oxide (PtAu NSs/rGO), without any surfactant, polymer, or seed involved. The obtained nanocomposites were applied for the catalytic reduction and removal of highly toxic chromium (VI) using formic acid as a model reductant at 50°C, showing the significantly enhanced catalytic activity and improved recyclability when compared with commercial Pt/C (50%) and home-made Au nanocrystals supported rGO (Au NCs/rGO). It demonstrates great potential applications of the catalyst in wastewater treatment and environmental protection. The eco-friendly route provides a new platform to fabricate other catalysts with enhanced catalytic activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The measurement of theophylline in human serum or plasma using gas chromatography and isotope dilution-mass spectrometry (GC-IDMS) taking other substituted xanthines into consideration.

    Science.gov (United States)

    Kress, Michael; Meissner, Dieane; Kaiser, Patricia; Hanke, Rainer; Wood, William Graham

    2002-01-01

    A method is described which uses a combination of gas chromatography and isotope dilution-mass spectrometry (GC-IDMS) to determine the concentration of theophylline (1,3-dimethyl xanthine) in human plasma or serum samples. The effects of similar substituted xanthines - namely theobromine (3,7-dimethyl xanthine), paraxanthine (1,7-dimethyl xanthine) 1,3-dimethyl-7-(2-hydroxyethyl) xanthine (internal standard HPLC) and caffeine (1,3,7-trimethyl xanthine) were tested to confirm the specificity of the method. The derivatisation of all xanthines was performed with N-methyl-N-trimethylsilyl trifluroacetamide (MSTFA). The internal standard used was 2-(13)C ,1,3-(15)N2-theophylline. The extraction and derivatisation procedures were examined in detail and optimised stepwise during the development of the method. High-performance liquid chromatography (HPLC) was used for comparison.

  7. Low Dose Theophylline Showed an Inhibitory Effect on the Production of IL-6 and IL-8 in Primary Lung Fibroblast from Patients with COPD

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2012-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by the abnormal and chronic lung inflammation. We hypothesized that lung fibroblasts could contribute to the local inflammation and investigated whether low dose theophylline had a beneficial effect on fibroblasts inflammation. Subjects undergoing lobectomy for bronchial carcinoma were enrolled and divided into COPD and control groups according to spirometry. Primary human lung fibroblasts were cultured from peripheral lung tissue distant to tumor tissue. There was a significant increase in both the mRNA expressions and protein levels for IL-6 and IL-8 in fibroblasts in COPD group, and the values were negatively correlated with lung function (P<0.05. For COPD fibroblasts, the protein levels of IL-6 and IL-8 decreased from 993.0 ± 738.9 pg/mL to 650.1 ± 421.9 pg/mL (P=0.014 and from 703.1 ± 278.0 pg/mL to 492.0 ± 214.9 pg/mL (P=0.001, respectively, with 5 μg/mL theophylline treatment. In addition, theophylline at the dose of 5 μg/mL reduced the increased production of IL-6 and IL-8 induced by 1 μg/mL LPS in primary human lung fibroblasts. Our data suggest that lung fibroblasts participate in the chronic inflammation in COPD by releasing IL-6 and IL-8, and low dose theophylline can alleviate the proinflammatory mediators’ production by fibroblasts.

  8. Pharmacokinetic profile of two different pharmaceutical forms of theophylline (a slow release tablet and a syrup after multiple dose administration to healthy human volunteers

    Directory of Open Access Journals (Sweden)

    Marcelo Nicolás Muscará

    1993-03-01

    Full Text Available Due to the narrow therapeutic range of theophyline, plasma concentrations of this drug are monitored in patients undergoing chronic therapy. Slow-release preparations avoid the fluctuations in plasma levels and improve patient compliance. In this study, we have compared the pharmacokinetic profiles of a theophylline slow-release tablet and a syrup form, when administered in multiple doses to healthy adult volunteers. The classification based upon releasing patterns is confirmed.

  9. Clinical efficacy of the transdermal tulobuterol patch in patients with chronic obstructive pulmonary disease: a comparison with slow-release theophylline.

    Science.gov (United States)

    Minami, Shuwa; Kawayama, Tomotaka; Ichiki, Masao; Nishiyama, Mamoru; Sueyasu, Yoshiko; Gohara, Rumi; Kinoshita, Masaharu; Koga, Hideyuki; Iwanaga, Tomoaki; Aizawa, Hisamichi

    2008-01-01

    There is insufficient evidence for the efficacy of a transdermal tulobuterol patch (TP), although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD). A randomized, controlled crossover study was conducted to evaluate the clinical efficacy and safety of the TP in 16 patients with COPD. Slow-release theophylline was used as a control drug. Following a 2-week run-in period, patients were randomly allocated to two groups by the envelope method; they then received the TP and theophylline for 4 weeks each by the crossover method. Pulmonary function tests, peripheral blood examination, and electrocardiography were performed before and after each treatment period. Patients recorded in diaries their symptom scores, numbers of administrations of inhaled beta(2) agonists, and presence/absence of adverse reactions. Patients receiving TP exhibited significant improvement in the number and ease of sputum expectoration and in cough frequency score and wheezing severity score compared with baseline (ptheophylline was non-significant. Assessment of quality of life by the St. George's Hospital Respiratory Questionnaire revealed that treatment with TP was associated with significant improvement in symptoms, impact, and total scores compared with baseline (ptheophylline gave only a non-significant improvement in total score. Neither drug caused significant changes in the results of physiological examinations or in pulse or blood pressure. There was no difference in safety between the treatments. Treatment of COPD patients with TP is more effective than with theophylline.

  10. Determination of caffeine, theobromine and theophylline in Mate beer and Mate soft drinks by high-performance thin-layer chromatography.

    Science.gov (United States)

    Oellig, Claudia; Schunck, Jacob; Schwack, Wolfgang

    2018-01-19

    Mate beer and Mate soft drinks are beverages produced from the dried leaves of Ilex paraguariensis (Yerba Mate). In Yerba Mate, the xanthine derivatives caffeine, theobromine and theophylline, also known as methylxanthines, are important active components. The presented method for the determination of caffeine, theobromine and theophylline in Mate beer and Mate soft drinks by high-performance thin-layer chromatography with ultraviolet detection (HPTLC-UV) offers a fully automated and sensitive determination of the three methylxanthines. Filtration of the samples was followed by degassing, dilution with acetonitrile in the case of Mate beers for protein precipitation, and centrifugation before the extracts were analyzed by HPTLC-UV on LiChrospher silica gel plates with fluorescence indicator and acetone/toluene/chloroform (4:3:3, v/v/v) as the mobile phase. For quantitation, the absorbance was scanned at 274nm. Limits of detection and quantitation were 1 and 4ng/zone, respectively, for caffeine, theobromine and theophylline. With recoveries close to 100% and low standard deviations reliable results were guaranteed. Experimental Mate beers as well as Mate beers and Mate soft drinks from the market were analyzed for their concentrations of methylxanthines. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Stimulation of Release of Adrenal Catecholamine by Adenosine 3′:5′-Cyclic Monophosphate and Theophylline in the Absence of Extracellular Ca2+

    Science.gov (United States)

    Peach, Michael J.

    1972-01-01

    Stimulation of catecholamine release was studied in the isolated adrenal of the cat during retrograde perfusion. Theophylline, adenosine 3′:5′-cyclic monophosphate (cyclic AMP), and dibutyryl-cyclic AMP stimulated catecholamine release in adrenal chromaffin tissue; adenosine, 2′-AMP, 3′-AMP, and 5′-AMP were ineffective. Addition of theophylline for 5-15 min had no effect on catecholamine release induced by KCl or nicotine, but it significantly increased the responses to cyclic AMP and its dibutyryl derivative. Glands perfused with Ca2+-free Locke's solution for 30-180 min rapidly lost their responsiveness to KCl or nicotine. In contrast, exposure to Ca2+-free medium for 180 min had no effect on secretory responses to either the cyclic nucleotides, themselves, or to methylxanthine-induced potentiation of cyclic AMP responses. Thus, dibutyryl-cyclic AMP, cyclic AMP, and theophylline do not require extracellular Ca2+ to release adrenal catecholamines. They may act by translocating intracellular bound Ca2+ or by a mechanism independent of calcium. PMID:4337240

  12. Methotrexate and its therapeutic antagonists caffeine and theophylline, target a motogenic T-cell mechanism driven by thrombospondin-1 (TSP-1).

    Science.gov (United States)

    Talme, Toomas; Bergdahl, Eva; Sundqvist, Karl-Gösta

    2016-05-01

    Methotrexate (MTX) is a widely used treatment for inflammatory diseases such as rheumatoid arthritis and psoriasis, based on the concept that it is immunosuppressive. Its mechanism of action, however, remains unclear, although it is thought to depend on adenosine. Caffeine and theophylline, which have several targets including adenosine receptors, have been shown to suppress the beneficial clinical effects of MTX. Here we show that MTX and caffeine and theophylline differentially affect a motogenic T-cell mechanism driven by endogenous thrombospondin-1 (TSP-1) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1). MTX stimulated TSP-1 expression and the motogenic TSP-1/TSP-1 receptor mechanism in primary human T cells, hence mimicking IL-2 and CXCL12, which similar to MTX, dampen inflammatory disease. SiRNA-mediated gene silencing of TSP-1 and LRP1 inhibited this stimulatory effect. Caffeine and theophylline inhibited the TSP-1/TSP-1 receptor mechanism by inhibiting LRP1 expression. These results indicate that the effect of MTX on T cells is immunoregulatory rather than immunosuppressive, and suggest a pathway dependent on TSP-1/TSP-1 receptor interactions for the regulation of immune responses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The neurophysiological effects of single-dose theophylline in patients with chronic stroke: A double-blind, placebo-controlled, randomized cross-over study.

    Science.gov (United States)

    Schambra, Heidi M; Martinez-Hernandez, Isis E; Slane, Kevin J; Boehme, Amelia K; Marshall, Randolph S; Lazar, Ronald M

    2016-09-21

    Reducing inhibitory neurotransmission with pharmacological agents is a potential approach for augmenting plasticity after stroke. Previous work in healthy subjects showed diminished intracortical inhibition after administration of theophylline. We assessed the effect of single-dose theophylline on intracortical and interhemispheric inhibition in patients with chronic stroke, in a double-blind, placebo-controlled, cross-over study. Eighteen subjects were randomly administered 300 mg of extended-release theophylline or placebo. Immediately and 5 hours following administration, transcranial magnetic stimulation was used to assess bihemispheric resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, and interhemispheric inhibition. Adverse effects on cardiovascular, neurological, and motor performance outcomes were also surveilled. Change between morning and afternoon sessions were compared across conditions. One week later, patients underwent the same assessments after crossing over to the opposite experimental condition. Subjects and investigators were blinded to the experimental condition during data acquisition and analysis. For both hemispheres, changes in intracortical or interhemispheric neurophysiology were comparable under theophylline and placebo conditions. Theophylline induced no adverse neurological, cardiovascular, or motor performance effects. For both conditions and hemipsheres, the baseline level of inhibition inversely correlated with its change between sessions: less baseline inhibition (i.e. disinhibition) was associated with a strengthening in inhibition over the day, and vice versa. A single dose of theophylline is well-tolerated by patients with chronic stroke, but does not alter cortical excitability. The inverse relationship between baseline inhibition and its change suggests the existence of a homeostatic process. The lack of effect on cortical inhibition may be related to an insufficiently

  14. Prophylactic theophylline for the prevention of severe renal dysfunction in term and post-term neonates with perinatal asphyxia: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Al-Wassia, H; Alshaikh, B; Sauve, R

    2013-04-01

    To examine the effect of prophylactic theophylline for the prevention of severe renal dysfunction in post-asphyxiated term and post-term infants. Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing prophylactic theophylline vs placebo in term infants following perinatal asphyxia. Four RCTs involving 197 infants were included in the meta-analysis. Compared with placebo, prophylactic theophylline was associated with a significant reduction in the incidence of severe renal dysfunction (pooled relative risk) using fixed-effects model was 0.38 (95% confidence interval, 0.25 to 0.57; Ptheophylline significantly reduce the incidence of severe renal dysfunction. However, because of the lack of information on the long-term renal and neurodevelopmental outcome and measured theophylline levels with relation to adverse effects observed, prudence with the clinical use of prophylactic theophylline is required. Additionally, the included trials were prior to the era of therapeutic hypothermia and thus inference of renal benefit in an infant undergoing hypothermia therapy cannot be made.

  15. Novel extraction and application of okra gum as a film coating agent using theophylline as a model drug.

    Science.gov (United States)

    Ogaji, Ikoni J; Hoag, Stephen W

    2014-04-01

    The purpose of this study was to investigate the effect of extraction and application of okra gum as an aqueous film coating agent. Powdered okra pods dispersed in demineralized water was heated at 80 ± 2(o)C for 30 minutes in the presence of sodium chloride. The filtrate was successively centrifuged at 4000 rpm for 30, 60, or 120 minutes and freeze dried. The samples were used as film former at different concentrations in aqueous film coating operations. Near infrared (nIR) absorption spectra, photomicrographs, and some physicochemical properties of the coated tablets were evaluated. The okra gum samples had different nIR spectra and possessed good processing and application quality due to relatively low viscosity. A six-fold concentration of this gum from the novel extraction yielded glossy theophylline tablets within a short time. A t (18) = 2.895, P okra samples at a flow rate of 3 ml/min for 100 minutes showed that F = 3.798, DF = 29, P extraction process enhanced the film coating potential of okra gum by delivering more solids on the substrate at a shorter time with improved operation efficiency.

  16. Effects of DU-6859a, a New Quinolone Antimicrobial, on Theophylline Metabolism in In Vitro and In Vivo Studies

    Science.gov (United States)

    Niki, Yoshihito; Itokawa, Kenichi; Okazaki, Osamu

    1998-01-01

    In vitro and in vivo studies were conducted to investigate the drug interaction between a new quinolone antimicrobial, DU-6859a, and theophylline (TP). The effect of DU-6859a on TP metabolism was evaluated in vitro by measuring the rate of TP metabolite formation by using human liver microsomes. DU-6859a inhibited the metabolism of TP, especially the formation of 1-methylxanthine, in vitro, but to a lesser extent than other drugs that are known to interact with TP. TP was administered alone (200 mg twice a day [b.i.d.] for 9 days) or in combination with DU-6859a (50 or 100 mg b.i.d. for 5 days) to six healthy subjects. DU-6859a administered at a dose of 50 mg resulted in no changes in serum TP concentrations, and slight increases in serum TP concentrations were observed at a dose of 100 mg. Moreover, the administration of 100 mg of DU-6859a resulted in decreases in all urinary TP metabolites, with significant differences. It appears that although DU-6859a has a weak inhibitory effect on TP metabolism in vitro, its concomitant use with TP at clinical dosage levels does not cause any adverse effects, showing only a slight increase in blood TP concentrations and a decrease in urinary metabolites. PMID:9661016

  17. Collaboration between HPMC and NaCMC in order to Reach the Polymer Critical Point in Theophylline Hydrophilic Matrices

    Directory of Open Access Journals (Sweden)

    L. Contreras

    2012-01-01

    Full Text Available Percolation theory has been applied in order to study the existence of critical points as well as the possibility to find a “combined percolation threshold” for ternary hydrophilic matrices prepared with HPMC, NaCMC, and theophylline. For this purpose, different batches of ternary as well as binary hydrophilic matrices have been prepared. Critical points have been found for binary hydrophilic matrices between 21.5 and 31.3% (v/v of HPMC and between 39 and 54% (v/v of NaCMC, respectively. In a previous work carried out with the same polymers but a much more soluble drug (KCl, it was demonstrated the existence of a partial collaboration between the polymers in order to establish the gel layer. In this work, it has been observed for the first time the need of a minimum concentration of one of the matrix-forming polymer (between 10 and 20% v/v, approximately for establishing an effective collaboration.

  18. Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.

    Science.gov (United States)

    Ceballos, A; Cirri, M; Maestrelli, F; Corti, G; Mura, P

    2005-01-01

    Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.

  19. Novel extraction and application of okra gum as a film coating agent using theophylline as a model drug

    Science.gov (United States)

    Ogaji, Ikoni J.; Hoag, Stephen W.

    2014-01-01

    The purpose of this study was to investigate the effect of extraction and application of okra gum as an aqueous film coating agent. Powdered okra pods dispersed in demineralized water was heated at 80 ± 2oC for 30 minutes in the presence of sodium chloride. The filtrate was successively centrifuged at 4000 rpm for 30, 60, or 120 minutes and freeze dried. The samples were used as film former at different concentrations in aqueous film coating operations. Near infrared (nIR) absorption spectra, photomicrographs, and some physicochemical properties of the coated tablets were evaluated. The okra gum samples had different nIR spectra and possessed good processing and application quality due to relatively low viscosity. A six-fold concentration of this gum from the novel extraction yielded glossy theophylline tablets within a short time. A t (18) = 2.895, P okra samples at a flow rate of 3 ml/min for 100 minutes showed that F = 3.798, DF = 29, P okra gum by delivering more solids on the substrate at a shorter time with improved operation efficiency. PMID:24959415

  20. Simultaneous determination of artificial sweeteners, preservatives, caffeine, theobromine and theophylline in food and pharmaceutical preparations by ion chromatography.

    Science.gov (United States)

    Chen, Q C; Wang, J

    2001-12-07

    A novel ion chromatographic method was proposed for the simultaneous determination of artificial sweeteners (sodium saccharin, aspartame, acesulfame-K), preservatives (benzoic acid, sorbic acid), caffeine, theobromine and theophylline. The separation was performed on an anion-exchange analytical column operated at 40 degrees C within 45 min by an isocratic elution with 5 mM aqueous NaH2PO4 (pH 8.20) solution containing 4% (v/v) acetonitrile as eluent, and the determination by wavelength-switching ultraviolet absorbance detection. The detection limits (signal-to-noise ratio 3:1) for all analytes were below the sub-microg/ml level. Under the experimental conditions, several organic acids, including citric acid, malic acid, tartaric acid and ascorbic acid, did not interfere with the determination. The method has been successfully applied to the analysis of various food and pharmaceutical preparations, and the average recoveries for real samples ranged from 85 to 104%. The levels of all analytes determined by this method were in good agreement with those obtained by the high-performance liquid chromatographic procedure. The results also indicated that ion chromatography would be possibly a beneficial alternative to conventional high-performance liquid chromatography for the separation and determination of these compounds.

  1. Collaboration between HPMC and NaCMC in order to Reach the Polymer Critical Point in Theophylline Hydrophilic Matrices

    Science.gov (United States)

    Contreras, L.; Melgoza, L. M.; Aguilar-de-Leyva, A.; Caraballo, I.

    2012-01-01

    Percolation theory has been applied in order to study the existence of critical points as well as the possibility to find a “combined percolation threshold” for ternary hydrophilic matrices prepared with HPMC, NaCMC, and theophylline. For this purpose, different batches of ternary as well as binary hydrophilic matrices have been prepared. Critical points have been found for binary hydrophilic matrices between 21.5 and 31.3% (v/v) of HPMC and between 39 and 54% (v/v) of NaCMC, respectively. In a previous work carried out with the same polymers but a much more soluble drug (KCl), it was demonstrated the existence of a partial collaboration between the polymers in order to establish the gel layer. In this work, it has been observed for the first time the need of a minimum concentration of one of the matrix-forming polymer (between 10 and 20% v/v, approximately) for establishing an effective collaboration. PMID:22919292

  2. Calculation of absolute free energy of binding for theophylline and its analogs to RNA aptamer using nonequilibrium work values

    Energy Technology Data Exchange (ETDEWEB)

    Tanida, Yoshiaki [Fujitsu Laboratories Ltd., 10-1 Morinosato-Wakamiya, Atsugi, Kanagawa (Japan)], E-mail: tanida@labs.fujitsu.com; Ito, Masakatsu; Fujitani, Hideaki [Fujitsu Laboratories Ltd., 10-1 Morinosato-Wakamiya, Atsugi, Kanagawa (Japan)

    2007-08-16

    The massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed [H. Fujitani, Y. Tanida, M. Ito, G. Jayachandran, C.D. Snow, M.R. Shirts, E.J. Sorin, V.S. Pande, J. Chem. Phys. 123 (2005) 084108]. As an application, we perform the binding affinity calculations of six theophylline-related ligands with RNA aptamer. Basically, our method is applicable when using many compute nodes to accelerate simulations, thus a parallel computing system is also developed. To further reduce the computational cost, the adequate non-uniform intervals of coupling constant {lambda}, connecting two equilibrium states, namely bound and unbound, are determined. The absolute binding energies {delta}G thus obtained have effective linear relation between the computed and experimental values. If the results of two other different methods are compared, thermodynamic integration (TI) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) by the paper of Gouda et al. [H. Gouda, I.D. Kuntz, D.A. Case, P.A. Kollman, Biopolymers 68 (2003) 16], the predictive accuracy of the relative values {delta}{delta}G is almost comparable to that of TI: the correlation coefficients (R) obtained are 0.99 (this work), 0.97 (TI), and 0.78 (MM-PBSA). On absolute binding energies meanwhile, a constant energy shift of {approx}-7 kcal/mol against the experimental values is evident. To solve this problem, several presumable reasons are investigated.

  3. Clinical efficacy of farcosolvin syrup (ambroxol-theophylline-guaiphenesin mixture) in the treatment of acute exacerbation of chronic bronchitis.

    Science.gov (United States)

    Yakoot, Mostafa; Salem, Amel; Omar, Abdel-Mohsen

    2010-08-09

    Acute exacerbations of chronic bronchitis (AECB) are defined as recurrent attacks of worsening bronchial inflammation that are marked by an increase in the volume of daily sputum produced, a change in color of the expectorated sputum, and worsening dyspnea. Farcosolvin (Pharco Pharmaceuticals, Alexandria, Egypt) is a mixture of ambroxol (15 mg); theophylline (50 mg); and guaiphenesin (30 mg), per 5 mL syrup. To test the clinical efficacy of Farcosolvin in the treatment of AECB in a randomized, single-blinded, controlled study design. One hundred patients with AECB were randomized to either Farcosolvin or guaiphenesin treatment groups, in addition to the standard medical treatment for their cases. Baseline clinical symptomatolgy of breathlessness, cough, and sputum severity scoring were compared before and after 3 and 7 days of treatment in both groups and the differences compared between groups. Changes in perceived improvement were also compared between groups using the Clinical Global Impression of Improvement or Change Scale (CGIC). There were statistically significant improvements in breathlessness and cough scores in both groups (pretreatment versus posttreatment at day 3 and at day 7; P < 0.05). There were highly statistically significant differences between groups in improvement in breathlessness and cough scores, after 3 and 7 days treatment, in favor of the Farcosolvin treatment group (P < 0.001). Out of 50 patients, 48 (96%) in the Farcosolvin-treated group rated their improvement on the CGIC scale as "much" and "very much" improved, while only 41 patients (82%) reported such a degree of improvement in the control group. The difference was statistically significant (P < 0.05). We concluded from our study that Farcosolvin syrup might be safe and effective in improving symptoms in cases of acute exacerbation of chronic bronchitis.

  4. Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine.

    Science.gov (United States)

    Zandvliet, Anthe S; Huitema, Alwin D R; de Jonge, Milly E; den Hoed, Rob; Sparidans, Rolf W; Hendriks, Vincent M; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

    2005-01-01

    The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.

  5. Formulation, characterization and in vitro evaluation of theophylline-loaded Eudragit RS 100 microspheres prepared by an emulsion-solvent diffusion/evaporation technique.

    Science.gov (United States)

    Jelvehgari, Mitra; Barar, Jaleh; Valizadeh, Hadi; Shadrou, Sanam; Nokhodchi, Ali

    2011-01-01

    The aim was to prepare theophylline-loaded Eudragit RS 100 microsphere to achieve sustained release pattern with relatively high production yield. To this end, microspheres were prepared by oil/oil solvent evaporation method using an acetone-methanol mixture and liquid paraffin system containing aluminum tristearate. Drug release profiles were determined at pH 1.2 and 7.4. Morphology and solid state of microspheres were examined using SEM, DSC, X-ray powder diffraction (XRPD), and FT-IR. As the ratio of acetone/methanol increased during the preparation of microspheres the size of microsphere was reduced. The highest drug loading efficiency (87.21%) was obtained for the microsphere containing a high ratio of polymer to drug (6:1) and high volume of acetone. SEM studies showed that the microspheres are almost spherical with a few pores and cracks at surfaces. The FT-IR, XRPD and DSC results ruled out any chemical interaction between theophylline and Eudragit. The microspheres prepared with low ratio of polymer to drug (1:2) showed faster dissolution rate than those with high polymer to drug ratio. The ratio of polymer to drug and the volume of polymer solvent were found to be the key factors affecting the release profile which could lead to microspheres with desired release behavior.

  6. Determination of theobromine, theophylline, and caffeine in by-products of cupuacu and cacao seeds by high-performance liquid chromatography.

    Science.gov (United States)

    Lo Coco, F; Lanuzza, F; Micali, G; Cappellano, G

    2007-01-01

    Theobromine, theophylline, and caffeine are determined simultaneously by a rapid and selective reversed-phase high-performance liquid chromatography (HPLC) method with UV detection in by-products of cupuacu and cacao seeds. The determination is carried out in the raw and roasted ground cupuacu seeds and in the corresponding powders obtained after pressure treatment. The by-products of both cupuacu seeds and cacao seeds are obtained under the same technological conditions. The HPLC method uses isocratic elution with a mobile phase of methanol-water-acetic acid (80:19:1) (v/v) at a flow rate of 1 mL/min and UV absorbance detection at 275 nm. Total elution time for these analytes is less than 10 min, and the detection limit for all analytes is 0.1 mg/g. The amounts of theobromine and caffeine found in all the cupuacu samples are one or more orders of magnitude lower than those from cacao. Theophylline is found in all cacao samples except for the roasted ground paste, and it is only found in the roasted ground paste in the cupuacu samples.

  7. On-line monitoring of vacuum drying of theophylline using NIR spectroscopy: solid-state transitions, water content and semi-empirical modeling.

    Science.gov (United States)

    Amira, Touil; Roman, Peczalski; Fethi, Zagrouba

    2016-11-01

    The aim of this work was to monitor in-line and at a real time, the solid-state forms during pharmaceuticals manufacturing. It concerns the dehydration behavior and the solid-state transitions of theophylline in an agitated vacuum contact dryer. First, a near infrared spectroscopy (NIRS) method was performed using a reflectance diffuse probe to measure the in-line and in-situ exact composition of the mixture of different forms of theophylline and water content during drying. A multivariate modeling has been investigated to build a robust model which can predict four components at the same time during drying process. The XRPD analysis was used as a reference method in the process of calibration of NIRS. The indicators of the accuracy in quantitative spectral analysis confirm the robustness of the model and the efficiency of the method of calibration. Second, the kinetics of solid state transformations were investigated. It was shown that the dehydration advanced first by the formation of the metastable anhydrate and after a lag time of the stable one. Once the stable form appeared, formation of the metastable form came to an end. The temperature was found out to be the main factor controlling the overall process rate but also the final contents of the stable and metastable anhydrates for the considered dryer and operating conditions range. Finally, a semi-empirical drying model was proposed and significant quantitative differences were found, particularly at the product temperature which was probably caused by the excessive simplicity of the model.

  8. Insight into the Structural Requirements of Theophylline-Based Aldehyde Dehydrogenase lAl (ALDHlAl) Inhibitors Through Multi-QSAR Modeling and Molecular Docking Approaches.

    Science.gov (United States)

    Abdul Amin, Sk; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2016-01-01

    Over expression of aldehyde dehydrogenase (ALDH1A1) is one of the vital hallmarks of the self-renewal and differentiational cancer stem cells (CSCs). Till now, no selective ALDH1A1 inhibitor is commercially available in the market. So there is an urgent need to explore some novel molecules which can selectively inhibit ALDH1A1 to combat cancer. Presently, our work deals with the development of QSAR models of some theophylline-based molecules by conventional 2D-QSAR, hologram QSAR (HQSAR), and Bayesian classification modeling. The descriptors identified from these QSAR models give avenues to modulate the structure of theophylline-based compounds to a desirable biological end point. Molecular docking study reveals the selectivity of these molecules towards ALDH1A1 (PDB: 4WP7) and important binding residues (GLY 125, 458; THR 129; TRP 178; TYR 297; PHE 171, 466; VAL 174, 460; MET 175; HIS 293 etc.) for the interaction with the receptors. The current study may help to design novel compounds as selective ALDH1A1 inhibitors.

  9. Synthesis and anticancer activity of silver(I)-N-heterocyclic carbene complexes derived from the natural xanthine products caffeine, theophylline and theobromine.

    Science.gov (United States)

    Mohamed, Heba A; Lake, Benjamin R M; Laing, Thomas; Phillips, Roger M; Willans, Charlotte E

    2015-04-28

    A new library of silver(I)-N-heterocyclic carbene complexes prepared from the natural products caffeine, theophylline and theobromine is reported. The complexes have been fully characterised using a combination of NMR spectroscopy, mass spectrometry, elemental analysis and X-ray diffraction analysis. Furthermore, the hydrophobicity of the complexes has been measured. The silver(I)-N-heterocyclic carbenes have been evaluated for their antiproliferative properties against a range of cancer cell lines of different histological types, and compared to cisplatin. The data shows different profiles of response when compared to cisplatin in the same panel of cells, indicating a different mechanism of action. Furthermore, it appears that the steric effect of the ligand and the hydrophobicity of the complex both play a role in the chemosensitivity of these compounds, with greater steric bulk and greater hydrophilicity delivering higher cytotoxicity.

  10. Pharmacokinetics of an ultralong sustained-release theophylline formulation when given twice daily in elderly patients with chronic obstructive pulmonary disease: monitoring implications.

    Science.gov (United States)

    Armijo, Juan A; Sánchez, Blanca M; Peralta, F Galo; González-Ruiz, Mario; Cuadrado, Antonio; Verdejo, Asunción; Cos, María A de; Arjona, Rafael

    2003-05-01

    The steady-state pharmacokinetics of an ultralong sustained release formulation of theophylline (Unilong) twice daily (bid) in elderly hospitalized patients suffering from chronic obstructive pulmonary disease (COPD) have been studied in order to establish guidelines for monitoring. The study was carried out in 37 patients (33 men), aged 60-87 years. Samples were collected from 0 to 12 h after the morning dose on day 9 of treatment with 250 mg bid (n=25) or 375 mg bid (n=12). Considerable variability in apparent clearance (range 0.33-1.49 ml/min per kg of ideal body weight), Css(min)/D (range 0.28-1.86), Css(max)/D (range 0.65-2.33) and (Css(max)-Css(min))/Css(avg) (range 0.18-0.80) was observed. There was no significant correlation between the patient's age and apparent clearance within this elderly population. The concentration-to-dose ratio and the relationship between the steady-state plasma concentration at different times during the dosage interval and Css(avg) are described. It is concluded that the interpatient variability in peak-trough fluctuation of this formulation was higher than that described in healthy volunteers by other investigators, and that the apparent clearance did not decrease with age within this elderly population with COPD. The importance of theophylline monitoring is emphasized and rules to estimate Css(avg) and Css(5h) from Css(0h) when only a single sample obtained before the morning dose is available are given. Copyright 2003 John Wiley & Sons, Ltd.

  11. Nitrogen-doped carbon nanotubes decorated poly (L-Cysteine) as a novel, ultrasensitive electrochemical sensor for simultaneous determination of theophylline and caffeine.

    Science.gov (United States)

    Wang, Yingzi; Ding, Yaping; Li, Li; Hu, Ping

    2018-02-01

    In present study, a novel and facile electrochemical sensor based on glassy carbon electrode (GCE) modified with nitrogen-doped carbon nanotubes (N-CNT) decorated with poly (L-Cysteine) (PLCY) were fabricated and applied for the simultaneous voltammetric determination of theophylline (THEO) and caffeine (CAF). The morphology and structure of multilayer film modified on the surface of glassy carbon electrode were investigated successfully by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM) and Raman Spectroscopy. And the properties of the modified electrode were investigated by Chronocoulometry (CC), Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV) were utilized to investigate the electrochemical behavior of THEO and CAF on the composite film modified electrode. The results showed that the determination towards THEO and CAF can be operated at the same potential window with the oxidation current peak separated and non-interfering respectively. Compared to the bare GCE, the PLCY/N-CNT/GCE can signally meliorate the electrocatalytic activity towards the oxidation of THEO and CAF with a remarkably increase in the anodic peak currents of 495.94% and 465.48%. Under the optimal conditions, the fabrication multilayer film sensor had excellent performances in determination towards THEO and CAF with a wide linear dynamic range from 0.10 to 70.0μM and 0.40-140.0μM, low detection limit (S/N = 3) of 0.033μM and 0.20μM, respectively. The PLCY/N-CNT/GCE sensor also had advantages as easy-made, high-sensitivity, stability and reproducibility. Moreover, it was successfully used to analyze the THEO and CAF in green tee, oral theophylline sustained release tablets and energy drink sample with a satisfactory result. Copyright © 2017. Published by Elsevier B.V.

  12. Solid-state thermal behavior and stability studies of theophylline-citric acid cocrystals prepared by neat cogrinding or thermal treatment

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Po-Chun; Lin, Hong-Liang [Department of Biotechnology, Yuanpei University, Hsin Chu, Taiwan (China); Wang, Shun-Li, E-mail: wangshunli@mail.ncyu.edu.tw [Department of Applied Chemistry, National Chia Yi University, Chia Yi, Taiwan (China); Lin, Shan-Yang, E-mail: sylin@mail.ypu.edu.tw [Department of Biotechnology, Yuanpei University, Hsin Chu, Taiwan (China)

    2012-08-15

    To investigate the thermal behavior of cocrystal formed between anhydrous theophylline (TP) and anhydrous citric acid (CA) by neat manual cogrinding or thermal treatment, DSC and FTIR microspectroscopy with curve-fitting analysis were applied. The physical mixture and 60-min ground mixture were stored at 55{+-}0.5 Degree-Sign C/40{+-}2% RH condition to determine their stability behavior. Typical TP-CA cocrystals were prepared by slow solvent evaporation method. Results indicate that the cogrinding process could gradually induce the cocrystal formation between TP and CA. The IR spectral peak shift from 3495 to 3512 cm{sup -1} and the stepwise appearance of several new IR peaks at 1731, 1712, 1676, 1651, 1557 and 1265 cm{sup -1} with cogrinding time suggest that the mechanism of TP-CA cocrystal formation was evidenced by interacting TP with CA through the intermolecular O-H{center_dot}{center_dot}{center_dot}O hydrogen bonding. The stability of 60-min ground mixture of TP-CA was confirmed at 55{+-}0.5 Degree-Sign C/40{+-}2% RH condition over a storage time of 60 days. - Garphical abstract: Cogrinding, thermal and solvent-evaporation methods might easily induce the theophylline-citric acid cocrystal formation. Highlights: Black-Right-Pointing-Pointer Cogrinding process could gradually induce the cocrystal formation between TP and CA. Black-Right-Pointing-Pointer The TP-CA cocrystal was formed through the intermolecular O-H{center_dot}{center_dot}{center_dot}O hydrogen bonding. Black-Right-Pointing-Pointer The 60-min TP-CA ground mixture was similar to the solvent-evaporated cocrystal. Black-Right-Pointing-Pointer The thermal-induced TP-CA cocrystal formation was confirmed by pre-heating the physical mixture to 152 Degree-Sign C. Black-Right-Pointing-Pointer The 60-min TP-CA ground mixture was stable at accelerated condition over a storage time of 60 days.

  13. Theophylline and Antiarrhythmics

    Science.gov (United States)

    Vandemark, F. L.

    Liquid chromatography has become a major analytical technique in the laboratory concerned with therapeutic drug monitoring. This acceptance arises from a number of important factors, including the unusual versatility of the technique, its potential use in the routine determination of drug substances, and the nondestructive nature of the detection systems commonly used.

  14. NTP Toxicology and Carcinogenesis Studies of Theophylline (CAS No. 58-55-9) in F344/N Rats and B6C3F1 Mice (Feed and Gavage Studies).

    Science.gov (United States)

    1998-08-01

    Theophylline is an alkaloid found in tea (Thea sinensis) and chocolate and is structurally related to caffeine and theobromine. Theophylline is used as a pharmaceutical agent. It stimulates the heart and central nervous system, relaxes the smooth muscles of the bronchi and blood vessels, and causes diuresis. The drug is used mainly as a bronchodilator in obstructive airway diseases, such as bronchial asthma, and for myocardial stimulation. Theophylline was nominated for toxicologic and carcinogenicity testing as a representative of the purine structural subclass, particularly because of its relationship to purines such as caffeine, 1-methyl-3-hydroxyguanine, and 3-hydroxy-1-methylxanthine, the latter two compounds having been shown to induce sarcomas in rats. Additional reasons for testing theophylline included its widespread use in humans as a pharmaceutical agent, its possible genotoxicity in vitro, and the lack of information on its potential toxicity and/or carcinogenicity under conditions of chronic oral usage. Based on reported teratogenicity and testicular toxicity, it was also recommended that reproductive studies be included in the evaluation of theophylline. The oral route of administration was selected because it is the primary route of human exposure, and the gavage route was selected because it mimics the pharmaceutical use of theophylline in humans. Male and female F344/N rats and B6C3F1 mice were given theophylline (greater than 99% pure) in feed or in corn oil by gavage for 16 days or 14 weeks or in corn oil by gavage for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, mouse bone marrow, and mouse peripheral blood. 16-DAY FEED STUDY IN RATS: Groups of five male and five female F344/N rats were given 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm theophylline in feed for 16 days, which resulted in approximate daily doses of 50, 100, 250, 450, or 1,000 mg theophylline/kg body weight to

  15. Magnetic Solid-phase Extraction with Fe3O4/Molecularly Imprinted Polymers Modified by Deep Eutectic Solvents and Ionic Liquids for the Rapid Purification of Alkaloid Isomers (Theobromine and Theophylline from Green Tea

    Directory of Open Access Journals (Sweden)

    Guizhen Li

    2017-06-01

    Full Text Available Different kinds of deep eutectic solvents (DES based on choline chloride (ChCl and ionic liquids (ILs based on 1-methylimidazole were used to modify Fe3O4/molecularly imprinted polymers (Fe3O4/MIPs, and the resulting materials were applied for the rapid purification of alkaloid isomers (theobromine and theophylline from green tea with magnetic solid-phase extraction (M-SPE. The M-SPE procedure was optimized using the response surface methodology (RSM to analyze the maximum conditions. The materials were characterized by Fourier transform infrared spectroscopy (FI-IR and field emission scanning electron microscopy (FE-SEM. Compared to the ILs-Fe3O4/MIPs, the DESs-Fe3O4/MIPs were developed for the stronger recognition and higher recoveries of the isomers (theophylline and theobromine from green tea, particularly DES-7-Fe3O4/MIPs. With RSM, the optimal recovery condition for theobromine and theophylline in the M-SPE were observed with ratio of methanol (80% as the washing solution, methanol/acetic acid (HAc (8:2 as the eluent at pH 3, and an eluent volume of 4 mL. The practical recoveries of theobromine and theophylline in green tea were 92.27% and 87.51%, respectively, with a corresponding actual extraction amount of 4.87 mg•g−1 and 5.07 mg•g−1. Overall, the proposed approach with the high affinity of Fe3O4/MIPs might offer a novel method for the purification of complex isomer samples.

  16. Magnetic Solid-phase Extraction with Fe₃O₄/Molecularly Imprinted Polymers Modified by Deep Eutectic Solvents and Ionic Liquids for the Rapid Purification of Alkaloid Isomers (Theobromine and Theophylline) from Green Tea.

    Science.gov (United States)

    Li, Guizhen; Wang, Xiaoqin; Row, Kyung Ho

    2017-06-25

    Different kinds of deep eutectic solvents (DES) based on choline chloride (ChCl) and ionic liquids (ILs) based on 1-methylimidazole were used to modify Fe3O4/molecularly imprinted polymers (Fe3O4/MIPs), and the resulting materials were applied for the rapid purification of alkaloid isomers (theobromine and theophylline) from green tea with magnetic solid-phase extraction (M-SPE). The M-SPE procedure was optimized using the response surface methodology (RSM) to analyze the maximum conditions. The materials were characterized by Fourier transform infrared spectroscopy (FI-IR) and field emission scanning electron microscopy (FE-SEM). Compared to the ILs-Fe3O4/MIPs, the DESs-Fe3O4/MIPs were developed for the stronger recognition and higher recoveries of the isomers (theophylline and theobromine) from green tea, particularly DES-7-Fe3O4/MIPs. With RSM, the optimal recovery condition for theobromine and theophylline in the M-SPE were observed with ratio of methanol (80%) as the washing solution, methanol/acetic acid (HAc) (8:2) as the eluent at pH 3, and an eluent volume of 4 mL. The practical recoveries of theobromine and theophylline in green tea were 92.27% and 87.51%, respectively, with a corresponding actual extraction amount of 4.87 mg•g-1 and 5.07 mg•g-1. Overall, the proposed approach with the high affinity of Fe3O4/MIPs might offer a novel method for the purification of complex isomer samples.

  17. Intervention Studies of Inhaled Corticosteroids Combined with Long-acting Theophylline or Long-acting β2-agonists in Patients with Moderate to Severe Asthma: A Randomized, Controlled Study.

    Science.gov (United States)

    Wang, Yan; Chen, Ping; Dai, Anna; Shang, Shengyun; Kong, Lingfei

    2016-12-01

    To evaluate and contrast the therapeutic effect and safety of fluticasone aerosol combined with theophylline tablets in patients with moderate to severe asthma, compared with salmeterol/fluticasone propionate aerosol. After a screening period, patients meeting the inclusion criteria were randomly assigned to the experiment group (fluticasone aerosol combined with theophylline tablets) or the control group (salmeterol/fluticasone aerosol combined with placebo tablets) for 12 weeks of treatment. The main outcome measurements were forced expiratory volume in 1 second and fractional concentration of exhaled nitric oxide value, whereas the secondary measures were forced vital capacity, peak expiratory flow value, and Asthma Control Test/Asthma Quality of Life Questionnaire score. Forty-four cases completed the course, with 23 cases in the experiment group and 21 cases in the control group. The forced expiratory volume in 1 second values of both groups were significantly improved from before (P theophylline tablets is worth considering for use in primary hospitals or for low-income populations. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  18. A physiologically based pharmacokinetic model characterizing mechanism-based inhibition of CYP1A2 for predicting theophylline/antofloxacin interaction in both rats and humans.

    Science.gov (United States)

    Pan, Xian; Wang, Ping; Hu, Nan; Liu, Li; Liu, Xiaodong; Xie, Lin; Wang, Guangji

    2011-01-01

    Clinical studies have revealed that some fluoroquinolones may cause severe adverse effects when co-administered with substrates of CYP1A2. Our previous study showed antofloxacin (ATFX) was responsible for mechanism-based inhibition (MBI) of the metabolism of phenacetin in rats. In the clinical setting, ATFX is likely to be administrated with theophylline (TP), which is mainly metabolized by CYP1A2. The aim of the present study was to investigate the possible mechanism of TP/ATFX interaction. In vitro studies showed that the inhibitory effect of ATFX on the formation of three TP metabolites depended on NADPH, the pre-inhibition time, and ATFX concentration, i.e., factors which characterize MBI. In vivo studies demonstrated that single-dose ATFX (20 mg/kg) did not affect the pharmacokinetic behavior of TP, but multidose ATFX (20 mg/kg b.i.d. for 7.5 days) significantly increased the AUC of TP, decreased the amount of three TP metabolites in urine, and suppressed hepatic microsomal activity. A physiologically based pharmacokinetic (PBPK) model characterizing MBI of the three TP metabolites was developed for predicting TP/ATFX interaction in rats; this model was further extrapolated to humans. The predicted results were in good agreement with observed data. All the results indicated that ATFX was responsible for MBI of the metabolism of TP, and the PBPK model characterizing MBI may give good prediction of TP/ATFX interaction.

  19. UV-Vis Spectrophotometry and Multivariate Calibration Method for Simultaneous Determination of Theophylline, Montelukast and Loratadine in Tablet Preparations and Spiked Human Plasma.

    Science.gov (United States)

    Hassaninejad-Darzi, Seyed Karim; Samadi-Maybodi, Abdolraouf; Nikou, Seyed Mohsen

    2016-01-01

    Resolution of binary mixtures of theophylline (THEO), montelukast (MKST) and loratadine (LORA) with minimum sample pre-treatment and without analyte separation has been successfully achieved by multivariate spectrophotometric calibration, together with partial least-squares (PLS-1), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV-Vis spectra of three compounds. The method of central composite design was used in the ranges of 2-14 and 3-11 mg L(-1) for calibration and validation sets, respectively. The models refinement procedure and their validation were performed by cross-validation. The minimum root mean square error of prediction (RMSEP) was 0.173 mg L(-1) for THEO with PCR, 0.187 mg L(-1) for MKST with PLS1 and 0.251 mg L(-1) for LORA with HLA techniques. The limit of detection was obtained 0.03, 0.05 and 0.05 mg L(-1) by PCR model for THEO, MKST and LORA, respectively. The procedure was successfully applied for simultaneous determination of the above compounds in pharmaceutical tablets and human plasma. Notwithstanding the spectral overlapping among three drugs, as well as the intrinsic variability of the latter in unknown samples, the recoveries are excellent.

  20. The effect of light and nitrogen availability on the caffeine, theophylline and allantoin contents in the leaves of Coffea arabica L.

    Directory of Open Access Journals (Sweden)

    Marcelo F. Pompelli

    2013-09-01

    Full Text Available Caffeine is the most abundant and important purine alkaloid derived from several important crop, such as coffee, tea, cocoa, guarana, and other plants. In tea and coffee plants, caffeine is predominantly produced in the young buds of leaves and in immature fruits. The effect of light-stimulating caffeine biosynthesis is uncertain, but our results clearly show that light, independent of N-availability, increases caffeine (26%, allantoin (47%, and theophylline (8% content in plants compared with those grown in a shaded (50% solar irradiation environment. Caffeine is the major low-molecular-weight nitrogenous compound in coffee plants, and at times, it functions as a chemical defense for new bud leaves. Therefore, the primary question that remains is whether caffeine can serve as a nitrogen source for other metabolic pathways. If so, plants grown under a low nitrogen concentration should promote caffeine degradation, with the consequent use of nitrogen atoms (e.g., in NH3 for the construction of other nitrogen compounds that are used for the plant’s metabolism. Our results provide strong evidence that caffeine is degraded into allantoin at low rates in N-deficient plants but not in N-enriched ones. By contrast, this degradation may represent a significant N-source in N-deficient plants.

  1. Simultaneous determination of caffeine, theophylline and theobromine in human plasma by on-line solid-phase extraction coupled to reversed-phase chromatography.

    Science.gov (United States)

    Emara, Samy

    2004-10-01

    A reversed-phase liquid chromatographic column switching system was described for the determination of caffeine (CF), theophylline (TH) and theobromine (TB) in human plasma with a direct injection procedure. A short protein-coated mu Bondapak CN silica pre-column (20 x 3 mm, i.d.) was used for enrichment of the drugs and clean up from weakly retained plasma components using phosphate buffer saline pH 7.4. After washing step, the retained drugs were flushed into a reversed-phase column (5 microm TSK gel ODS-80 TM, 150 x 4.6 mm i.d.) with a mobile phase of methanol-0.01 M phosphate buffer, pH 3.5 (30:70, v/v) for the final separation. The eluent was monitored with a UV detector at 275 nm. The resulting chromatograms showed no interference from endogenous plasma components. A linear relationship between the concentration of drug and peak height was confirmed in the range of 0.5-20 microg/mL for all drugs. High extraction recoveries from plasma ranging from 96.12 to 100.32% were achieved. Validation of the method was examined performing intra- and inter-day accuracy and precision and was found to be satisfactory. The coefficients of variation of the three drugs were less than 3% for intra-day and less than 4% for inter-day run assays.

  2. Predictive evaluation of pharmaceutical properties of direct compression tablets containing theophylline anhydrate during storage at high humidity by near-infrared spectroscopy.

    Science.gov (United States)

    Otsuka, Yuta; Yamamoto, Masahiro; Tanaka, Hideji; Otsuka, Makoto

    2015-01-01

    Theophylline anhydrate (TA) in tablet formulation is transformed into monohydrate (TH) at high humidity and the phase transformation affected dissolution behavior. Near-infrared spectroscopic (NIR) method is applied to predict the change of pharmaceutical properties of TA tablets during storage at high humidity. The tablet formulation containing TA, lactose, crystalline cellulose and magnesium stearate was compressed at 4.8 kN. Pharmaceutical properties of TA tables were measured by NIR, X-ray diffraction analysis, dissolution test and tablet hardness. TA tablet was almost 100% transformed into TH after 24 hours at RH 96%. The pharmaceutical properties of TA tablets, such as tablet hardness, 20 min dissolution amount (D20) and increase of tablet weight (TW), changed with the degree of hydration. Calibration models for TW, tablet hardness and D20 to predict the pharmaceutical properties at high-humidity conditions were developed on the basis of the NIR spectra by partial least squares regression analysis. The relationships between predicted and actual measured values for TW, tablet hardness and D20 had straight lines, respectively. From the results of NIR-chemometrics, it was confirmed that these predicted models had high accuracy to monitor the tablet properties during storage at high humidity.

  3. Solid-state thermal behavior and stability studies of theophylline-citric acid cocrystals prepared by neat cogrinding or thermal treatment

    Science.gov (United States)

    Hsu, Po-Chun; Lin, Hong-Liang; Wang, Shun-Li; Lin, Shan-Yang

    2012-08-01

    To investigate the thermal behavior of cocrystal formed between anhydrous theophylline (TP) and anhydrous citric acid (CA) by neat manual cogrinding or thermal treatment, DSC and FTIR microspectroscopy with curve-fitting analysis were applied. The physical mixture and 60-min ground mixture were stored at 55±0.5 °C/40±2% RH condition to determine their stability behavior. Typical TP-CA cocrystals were prepared by slow solvent evaporation method. Results indicate that the cogrinding process could gradually induce the cocrystal formation between TP and CA. The IR spectral peak shift from 3495 to 3512 cm-1 and the stepwise appearance of several new IR peaks at 1731, 1712, 1676, 1651, 1557 and 1265 cm-1 with cogrinding time suggest that the mechanism of TP-CA cocrystal formation was evidenced by interacting TP with CA through the intermolecular O-H···O hydrogen bonding. The stability of 60-min ground mixture of TP-CA was confirmed at 55±0.5 °C/40±2% RH condition over a storage time of 60 days.

  4. Determination of ambroxol hydrochloride, guaifenesin, and theophylline in ternary mixtures and in the presence of excipients in different pharmaceutical dosage forms.

    Science.gov (United States)

    Abdelwahab, Nada S

    2012-01-01

    Determination of ternary mixtures of ambroxol hydrochloride, guaifenesin, and theophylline with minimum sample pretreatment and without analyte separation has been successfully achieved by using chemometric and RP-HPLC methods. The developed chemometric models are partial least squares (PLS) and genetic algorithm coupled with PLS. Data of the analyses were obtained from UV-Vis spectra of the studied drugs in different concentration ranges. These models have been successfully updated to be applied for determination of the proposed drugs in Farcosolvin syrup and in the presence of a syrup excipient (methyl paraben). In the developed RP-HPLC method, chromatographic runs were performed on an RP-C18 analytical column with the isocratic mobile phase 0.05 M phosphate buffer-methanol-acetonitrile-triethylamine (63.5 + 27.5 + 9 + 0.25, v/v/v/v, pH 5.5 adjusted with orthophosphoric acid) at a flow rate of 1.2 mL/min. The analytes were detected and quantified at 220 nm. The method was optimized in order to obtain good resolution between the studied components and to prevent interference from methyl paraben. Method validation was performed with respect to International Conference on Harmonization guidelines and the validation acceptance criteria were met in all cases. The proposed methods can be considered acceptable for QC of the studied drugs in pharmaceutical capsules and syrup. The results obtained by the suggested chemometric methods for determination of the studied mixture in different pharmaceutical preparations were statistically compared to those obtained by applying the developed RP-HPLC method, and no significant difference was found.

  5. Development of the insulin secretion mechanism in fetal and neonatal rat pancreatic B-cells: response to glucose, K+, theophylline, and carbamylcholine

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    A.C. Mendonça

    1998-06-01

    Full Text Available We studied the development of the insulin secretion mechanism in the pancreas of fetal (19- and 21-day-old, neonatal (3-day-old, and adult (90-day-old rats in response to stimulation with 8.3 or 16.7 mM glucose, 30 mM K+, 5 mM theophylline (Theo and 200 µM carbamylcholine (Cch. No effect of glucose or high K+ was observed on the pancreas from 19-day-old fetuses, whereas Theo and Cch significantly increased insulin secretion at this age (82 and 127% above basal levels, respectively. High K+ also failed to alter the insulin secretion in the pancreas from 21-day-old fetuses, whereas 8.3 mM and 16.7 mM glucose significantly stimulated insulin release by 41 and 54% above basal levels, respectively. Similar results were obtained with Theo and Cch. A more marked effect of glucose on insulin secretion was observed in the pancreas of 3-day-old rats, reaching 84 and 179% above basal levels with 8.3 mM and 16.7 mM glucose, respectively. At this age, both Theo and Cch increased insulin secretion to close to two-times basal levels. In islets from adult rats, 8.3 mM and 16.7 mM glucose, Theo, and Cch increased the insulin release by 104, 193, 318 and 396% above basal levels, respectively. These data indicate that pancreatic B-cells from 19-day-old fetuses were already sensitive to stimuli that use either cAMP or IP3 and DAG as second messengers, but insensitive to stimuli such as glucose and high K+ that induce membrane depolarization. The greater effect of glucose on insulin secretion during the neonatal period indicates that this period is crucial for the maturation of the glucose-sensing mechanism in B-cells.

  6. Synthesis and investigation of the physicochemical properties of 2-(5-((theophylline-7'-ylmethyl-4-phenyl-4H-1,2,4-triazole-3-ylthio-acetic acid salts

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    A. S. Gotsulya

    2014-02-01

    Full Text Available Introduction. In last decades considerable interest to the search of biologically active compounds in series of azole derivatives is indicated. This is mainly connected with the successful use of several drugs with heterocyclic system in the structure. Analysis of the pharmacological properties of heterocyclic nitrogen–containing compounds of the known groups let us to suggest, that the triazole substituent is an important pharmacophore fragment, responsible for the availability of diverse physiological activity. In addition, it causes a little toxicity. Considerable attention belongs to synthesis and research of the biological activity of 1,2,4-triazoles derivatives. The great importance also has research of the influence of heterocyclic fragments of different nature in combination in one molecule on the activity of the synthesized compounds. Like different synthons in the structure of 1,2,4-triazoles in various kinds of biological activity of the reaction products with an aim of new and highly efficient low-toxicity compounds reception. The aim of work was to study synthesis and properties of substances among salts of 2-(5-((theophylline-7'-ylmethyle-4-phenyle-4Н-1,2,4-triazole-3-ylthioacetate acid. Materials and methods of the research. In the process as a starting material for reception of new series of compounds theophylline has been chosen. It is important to note, that by the diversity and strength of pharmacological effects, which appears, this structure takes its rightful place among heterocyclic compounds. Through the series of the successive stages 4-phenyle-5-(1',3'-dimethylxantine-7'-ylmethyle-1,2,4-triazole-3-thiol was obtained from the theophylline. Research of the physico-chemical properties of the received compounds conducted according to methods, described in the State Pharmacopoeia of Ukraine. open capillary method, elemental analysis (Elementar Vario L cube (CHNS. 1H NMR spectra of compounds were recorded with a

  7. Development and in vitro evaluation of extended-release theophylline matrix capsules Desenvolvimento e avaliação in vitro de cápsulas de teofilina de liberação prolongada

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    Vanessa Alves Pinheiro

    2007-06-01

    Full Text Available Polymers like cellulose (MethocelTM K100MPRCR, K15MPRCR and E4MCR at different proportions (15-35% were used to slow the release of theophylline (100 mg from capsules. Volumetric method for powder filling capsules was used to prepare the capsules. Drug release from capsules was performed using apparatus 1, at 100 rpm and 900 mL of intestinal medium without enzymes (pH 7.5, at 37 °C, following the USP 28th ed. (Test 8. Dissolution profiles were compared to two batches of commercial extended-release capsules. Capsules compounded with 35% (wt/wt of MethocelTM E4MCR showed dissolution profile according to the official especifications. Similar results were reproduced with other ten compounded batches. Commercial extended-release capsules containing theophylline pellets (100 mg showed quick drug release when submitted to the same test, indicating that, in these conditions, the capsules did not show prolonged release. Mathematical models like zero-order, first-order and Higuchi were applied in kinetic studies of theophylline release from the compounded capsules. Polymers were efficient to control the release of theophylline in capsules involving diffusion and erosion as mechanisms, and that first-order model was the best fitted one for theophylline matrix capsules. These results support that compounded extended-release capsules can be prepared, since the drug release tests can be done.Cápsulas de liberação modificada contendo 100 mg de teofilina foram preparadas com polímeros derivados da celulose (Methocel® K100MPRCR, K15MPRCR e E4MCR em diferentes concentrações, 15-35%, empregando-se o método volumétrico. Estudos de liberação do fármaco foram realizados de acordo com a Farmacopéia Americana 28 ed., (Teste 8, empregando aparato 1, rotação de 100 rpm e temperatura de 37 ºC em 900 mL de meio fluido intestinal sem enzimas (pH 7,5. Os perfis de dissolução foram comparados ao de duas especialidades farmacêuticas comerciais. A formula

  8. Formulation and in vitro evaluation of theophylline-Eudragit® sustained-release tablets Desenvolvimento e avaliação in vitro de comprimidos de liberação prolongada de teofilina preparados com Eudragit®

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    Evelyn Ojoe

    2005-09-01

    Full Text Available Tablets containing theophylline (66.67% based on a Eudragit® RS 30D and NE 30D matrices containing 10% to 30% of either of the polymer were produced by compression method. The influence of the different proportions of methacrylic esters, the use of lactose and tribasic calcium phosphate as diluents and also the effects of the addition of magnesium stearate as a hydrophobic agent lubricant on the theophylline release, were studied. Physicochemical analyses and drug content was evaluated. In vitro drug release studies were carried out in simulated gastric fluid without pepsin (pH1.2 and simulated intestinal fluid without pancreatin (pH7.5. A relatively prolonged release of theophylline from the polymer matrices for a 7 hr-release period was detected. Magnesium stearate at 0.5% and Eudragit® NE 30D at 10% was considered a better sustained-release matrix compressed theophylline tablets comparing with Eudragit® RS 30D in the same conditions (USP. Results from physicochemical analyses were in accordance with specifications. The release patterns were analyzed from the viewpoint of square-root of time and as a first-order, zero-order kinetics, and Higuchi. Additionally, half-life of release (Td50% and dissolution rates (kd were calculated. Higuchi was the model that better fitted theophylline kinetic, and diffusion controlled was involved.Comprimidos contendo teofilina (66.67% e polímeros de Eudragit® NE 30D e RS 30D entre 10 e 30% foram produzidos por compressão. A influência das diferentes proporções de ésteres do ácido metacrílico, uso da lactose e fosfato de cálcio tribásico como diluente, bem como os efeitos da adição de estearato de magnésio como agente lubrificante hidrofóbico na liberação da teofilina foram estudados. Análises físico-químicas e teor de fármaco foram avaliados. Estudos da liberação do fármaco in vitro foram conduzidos em fluido gástrico simulado (pH 1,2 e fluido intestinal simulado sem pancreatina (p

  9. Influence of cellulose polymers type on in vitro controlled release tablets containing theophylline Desenvolvimento e avaliação de comprimidos matriciais de teofilina baseados em ésteres da celulose

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    Evelyn Ojoe

    2007-12-01

    Full Text Available In this study, the effect of ethylcellulose (EC and 6 types of hydroxypropylmethylcellulose (Methocel® K100M, K100MPRCR, K15MPRCR, K4MPRCR, K4M PR and E4MCR on release profile of theophylline from matrix tablets was evaluated. Formulations tablets were prepared by either wet granulation or direct compression technique. The tablets were evaluated for physical characteristics and in vitro release of drug was performed as described in USP 30 ed. (Test 3. All formulations with cellulose polymer produced tablets easily and with physicals characteristics in accordance with official limits. Drug dissolution tests showed that formulations with 15% of Methocel® K4MPR, 15% of Methocel® K4MPRCR and 30% of Ethocel® N10STD, obtained by direct compression method, complied with official specifications, in terms of release profile and diffusion was the main mechanism involved in theophylline delivery.Os efeitos das variáveis das formulações na liberação da teofilina a partir da hidroxipropilmetilcelulose (HPMC e etilcelulose (EC em comprimidos matriciais foram estudados. Formulações de comprimidos foram preparadas pelos métodos da granulação úmida ou compressão direta usando diferentes viscosidades de HPMC. Propriedades físico-químicas dos comprimidos e liberação do fármaco foram estudadas conforme dissolução descrita no Teste 3 da Farmacopéia Americana 30ed. Ensaios "in vitro" mostraram que as formulações com 15% de Methocel® K4MPR, 15% de Methocel® K4MPRCR e 30% de Ethocel® N10STD obtidas por compressão direta apresentaram bom perfil de liberação de teofilina e a difusão foi o principal mecanismo envolvido na liberação.

  10. Self-assembly of the hydrogel polymer chain consisting of chitosan and chondroitin sulphate in the presence of theophylline;Propriedades de higrogeis constituidos de quitosana e sulfato decondroitina na presenca de teofilina intumescidos em diferentes pHs

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Lais C.; Piai, Juliana F.; Fajardo, Andre R.; Rubira, Adley F.; Muniz, Edvani C., E-mail: ecmuniz@uem.b [Universidade Estadual de Maringa (GMPC/UEM), PR (Brazil). Grupo de Materiais Polimericos e Compositos

    2009-07-01

    In this work, polyelectronic complex (PEC) consisting of two polysaccharides were developed. One is chitosan (QT), cationic polymer, produced by the chitin deacetylation and the other is chondroitin sulphate (CS), anionic polymer, extracted from bovine or porcine aorta. The PECs were prepared in the presence of theophylline (TEO) for evaluating the influence of this drug in the polymer chains reorganization, as well as, studying the mechanical properties and release of SC and TEO in aqueous solutions on different pH conditions. By the obtained results, it was observed that the 84QT/15SC/TEO (% in weight) hydrogel is pH responsive because the CS releasing is more effective at pH 8, while the release of the TEO is higher at pH 2. The hydrogel showed mechanical properties more resistant to pH 2, 8 and 10 and this was attributed to interactions between the polymer chains. Finally, the X-rays profile showed the presence of peaks associated to reorganization of the chains in the hydrogel is at times larger than the hydrogel in the absence of solute. (author)

  11. Efeito da teofilina associada ao beta2-agonista inalatório de curta ou longa duração, em pacientes com doença pulmonar obstrutiva crônica estável: revisão sistemática Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review

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    Eliane Cristina Zacarias

    2007-04-01

    Full Text Available OBJETIVOS: Avaliar se o tratamento com teofilina associada ao beta2-agonista inalatório de curta ou longa duração é mais eficaz que o placebo e que o uso isolado de cada um dos fármacos, para os pacientes com doença pulmonar obstrutiva crônica estável. MÉTODOS: Realizou-se uma revisão sistemática com metanálise, sendo selecionados todos os ensaios clínicos aleatórios e duplo-cegos encontrados na literatura. RESULTADOS: Foram incluídos oito estudos. Teofilina associada ao beta2-agonista vs. placebo: houve melhora estatisticamente significante para o VEF1 (L, com média 0,27 (IC95% 0,11 a 0,43; e para a dispnéia, com média -0,78 (IC95% -1,26 a -0,29. Teofilina associada ao beta2-agonista vs. beta2-agonista isolado: nenhuma das metanálises realizadas detectou diferença entre os grupos. Teofilina associada ao beta2-agonista vs. teofilina isolada: houve melhora estatisticamente significante para a dispnéia, com média -0,19 (IC95% -0,34 a -0,04. CONCLUSÕES: Em pacientes com doença pulmonar obstrutiva crônica estável: 1 teofilina associada ao beta2-agonista é mais eficaz que o placebo, em relação ao VEF1 e dispnéia; 2a teofilina associada ao beta2-agonista é mais eficaz que a teofilina isolada, em relação à dispnéia; e 2b teofilina associada ao beta2-agonista não é mais eficaz que o beta2-agonista isolado, para quaisquer das variáveis estudadas.OBJECTIVES: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS: A total of eight studies were included. In comparing the effect of theophylline combined with beta2-agonists to that of a placebo, we found a

  12. Liberación de la teofilina a partir de matrices hidrófilas que contienen algfinato de sodio procedentes de Sargassum cymosum (Phaeofphyta Release of theophylline from hydrophilic matrices containing sodium alginate from seasonal Sargassum cymosum (Phaeophyta

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    Itamar Francisco Andreazza

    2009-08-01

    Full Text Available The sodium alginate extracted from seasonal Sargassum cymosum samples (autumn, winter, spring and summer in Paciência Beach (Penha- SC-Brazil showed a viscosity of 18.3, 33.5, 62.6 and 34.2 mPa·s, respectively. Theophylline tablets(60 mg containing 35 % of sodium alginate samples were analyzed by dissolution profile in a dissolution device at 100 rev×min-1 and 37 °C, using water as dissolution medium, during 6 h. Tablets with the lesser viscous sodium alginate sample (autumn showed a complete disintegration and drug release after 1 h. Despite all others tablets have exhibited the same drug release mechanism, by diffusion, the winter sodium alginate tablets released > 90 % of theophylline after 3 h, while spring and summer sodium alginate tablets showed similar dissolution profile with a release > 90 % of drug after 6 h. In general, the less viscous polymers showed a faster drug release, but probably other characteristics beside viscosity have played role in this process.El alginato de sodio extraído de muestras estacionales de Sargassum cymosum (otoño, invierno, primavera y verano en la Playa de la Paciencia (Penha-SC-Brasil mostró viscosidad de 18,3, 33,5, 62,6 y 34,2 mPa·s, respectivamente. Tabletas de teofilina (60 mg que contenían 35 % de muestras de alginato de sodio fueron analizadas a través del perfil de disolución, en un disolutor a 100 rev×min-1 y 37 ºC, utilizando agua como medio de disolución, durante 6 h. Las tabletas con la muestra de alginato de sodio menos viscosa (otoño mostraron completa desintegración y liberación del fármaco después de 1 h. A pesar de que todas las demás tabletas mostraron el mismo mecanismo de liberación del fármaco, por difusión, las tabletas con la muestra de alginato de sodio de invierno liberó > 90 % de la teofilina después de 3 h, mientras las tabletas de alginato de sodio de primavera y verano presentaron un perfil de disolución semejante con liberación > 90 % de f

  13. Determination of theophylline by HPLC and GC-IDMS, the effect of chemically similar xanthine derivatives on the specificity of the method and the possibility of paracetamol as interfering substance.

    Science.gov (United States)

    Kress, Michael; Meissner, Dieane; Kaiser, Patricia; Hanke, Rainer; Wood, William Graham

    2002-01-01

    The aim of this study was to develop and compare high-performance liquid chromatography (HPLC) and gas chromatography coupled with isotope dilution-mass spectrometry (GC-IDMS) methods with a common extraction procedure for the determination of substituted xanthines in biological matrices such as serum and urine. For HPLC both isocratic and gradient methods were evaluated. Difficulties occurred in separation of all 6 xanthines of interest - uric acid, theobromine, theophylline, paraxanthine, caffeine and 1,3-dimethyl-7-(2-hydroxyethyl) xanthine as internal standard. In addition, paracetamol was seen to interfere at higher concentrations, which meant that a system had to be developed to separate all 7 components of interest. The final solution chosen consisted of precipitation of serum samples with 6 mol/l trichloroacetic acid followed by neutralisation with 3 mol/l KOH and chromatography on a 150 x 4.6 mm Nautilus C-18 column (Macherey & Nagel) using an isocratic elution consisting of 0.02 mol/l acetate-phosphate buffer, pH 3.0 containing 9.6% v/v acetonitrile and monitoring at 273 +/- 7 nm. Comparisons with GC-IDMS and FPIA were acceptable. Run times of 10 minutes were possible. An additional "safe time" of 5 minutes was allowed to elute any substances with similar absorption maxima which were sometimes present in commercial control sera. Precision of the method was 1.64% (intra-assay) and 2.87% (inter-assay) at 4.1 mg/l and 1.51% respectively 2.15% at 25 mg/l including extraction and measurement steps. Recovery was between 86 and 101% between 1.25 and 100 mg/l and peak time deviations for all 7 components between 0.07% and 0.34% (coefficient of variation) in 7 consecutive measurements.

  14. Determinação simultânea de teobromina, teofilina e cafeína em chás por cromatografia líquida de alta eficiência Simultaneous determination of theobromine, theophylline and caffeine in teas by high performance liquid chromatography

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    Adriana Barreto Alves

    2002-06-01

    Full Text Available Para a realização deste trabalho, foram analisadas 10 amostras de diferentes tipos e marcas de chás com o objetivo de se quantificar teobromina, teofilina e cafeína simultaneamente. Para tanto, otimizou-se técnica de cromatografia líquida de alta eficiência (CLAE baseada na ISO 10095 (1992, utilizando-se coluna Inertsil ODS-3 (150x4 mm, 5 mm, fase móvel de ácido acético 1% + acetonitrila (95:5, v/v, fluxo de 1 mL/min e detector de UV/VIS ajustado em 273 nm. Os resultados de cafeína obtidos por esse método foram comparados com os obtidos por um método espectrofotométrico de acordo com Schormüller (1970. Não houve diferença significativa nos resultados de cafeína nas amostras de chá preto obtidos pelos dois métodos. As amostras de chá preto foram as que apresentaram maiores teores de teobromina e cafeína e nenhuma das amostras apresentou quantidades significativas de teofilina.To carry out this study, 10 samples of different kinds and brands of teas were analyzed with the purpose of quantifying simultaneously theobromine, theophylline and caffeine. For this, high performance liquid chromatography (HPLC was used based on ISO 10095 (1992. The conditions were: a reversed phase column (Inertisil ODS-3, 150x4 mm, 5 mm; acetic acid 1% + acetonitrile (95:5, v/v as mobile phase; flow of 1 ml/min and UV-VIS detector set at 273 nm. The results of caffeine obtained by this method were compared with those using a spectrophotometric method according to Schormüller (1970. In the case of black tea, no difference was observed in the caffeine, by both methods. The samples of black tea had the highest amounts of theobromine and caffeine and no sample had a significant amount of theophylline.

  15. Dgroup: DG01609 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01609 DGroup Xanthine-type bronchodilator -fylline, -phylline ... DG01061 ... Theophylline ... D00371 ... Theophyllin...e (JP17) ... D01712 ... Theophylline sodium acetate (JAN) ... D06103 ... Theophylline (USP) ... D06104 ... Theophylline

  16. Development and evaluation of an optimised theophylline timed ...

    African Journals Online (AJOL)

    Background: Chronopharmaceutics is a branch of pharmaceutics devoted to the design and evaluation of drug delivery systems that releases a bioactive agent at a rhythm that ideally matches the biological requirement of a given disease. Aim: To develop and evaluate an optimized compression coated timed release tablet ...

  17. Preparation, Characterization and In vitro Evaluation of Theophylline ...

    African Journals Online (AJOL)

    of Starch and Vegetable Protein Processing, Ministry of Education, South China University of Technology, Guangzhou 510640,. China. *For correspondence: .... a TM-3000 scanning electron microscope (Hitachi, Japan) in the charge-up ..... molecules, part of its primary amino groups lost their positive charges after they ...

  18. Preparation, Characterization and In vitro Evaluation of Theophylline ...

    African Journals Online (AJOL)

    Methods: SPI-based nanoparticles were prepared with soy protein-dextran conjugates obtained by titanium dioxide (TiO2) photocatalysis using a simple ionic gelation method. Formation of the conjugates was monitored spectrophotometrically for free amino group content (A340nm) and by Fourier transform infrared ...

  19. Differential pulse voltammetric determination of theophylline at poly ...

    African Journals Online (AJOL)

    amino-3-hydroxynaphthalene sulfonic acid (AHNSA) in 0.1 M HNO3. Cyclic voltammetry (CV) was used to study the electrochemical properties of the polymer film. The polymer film-modified electrode was used to electrochemically detect ...

  20. differential pulse voltammetric determination of theophylline at poly ...

    African Journals Online (AJOL)

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    Scheme 1. Mechanism for the oxidation of TP at poly(AHNSA)/GCE. As can be seen from Figure 5C, the peak current response decreased with increasing pH values from 2.0 to 7.0 which is in agreement with the previous report [18]. The sharpness of the peaks also decreases along with increasing the pH of the solution.

  1. Dgroup: DG01061 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01061 Chemical ... DGroup Theophylline ... D00371 ... Theophylline (JP17) ... D01712 ... Theophylline... sodium acetate (JAN) D06103 ... Theophylline (USP) D06104 ... Theophylline sodium glycinate (USP) Other

  2. Dgroup: DG01892 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ne ... D08555 ... Tacrine (INN) ... D02068 ... Tacrine hydrochloride (USP) DG01061 ... Theophylline ... D00371 ... Theophylline (JP17) ... D01712 ... Theophy...lline sodium acetate (JAN) ... D06103 ... Theophylline (USP) ... D06104 ... Theophylline

  3. 76 FR 9789 - Determination That Theophylline Oral Solution, 80 Milligrams/15 Milliliters, Was Not Withdrawn...

    Science.gov (United States)

    2011-02-22

    ... the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants... drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing... ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug...

  4. High-dose inhaled corticosteroids or addition of theophylline in patients with poorly controlled asthma?

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    Pilar Celis

    2015-08-01

    Full Text Available Existen varias estrategias para el manejo de los pacientes asmáticos con mal control a pesar del tratamiento habitual. Dentro de las alternativas terapéuticas se encuentra aumentar las dosis de corticoides inhalados o utilizar teofilina. Sin embargo, esta última se asocia a importantes efectos adversos. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos una revisión sistemática que incluye cuatro estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si teofilina o el uso de dosis altas de corticoides inhalados logran un mejor control sintomático o reducción de las exacerbaciones en pacientes asmáticos no controlados porque la certeza de la evidencia es muy baja.

  5. CONTROLLED-RELEASE OF THEOPHYLLINE MONOHYDRATE FROM AMYLODEXTRIN TABLETS - IN-VITRO OBSERVATIONS

    NARCIS (Netherlands)

    VANDERVEEN, J; TEWIERIK, GHP; VANDERWAL, L; EISSENS, AC; LERK, CF

    Amylodextrin is a linear dextrin and can be produced by enzymatic hydrolysis of the alpha-1,6 glycosidic bonds of amylopectin. Tablets compacted from pure amylodextrin showed good binding properties and did not disintegrate in aqueous media. Extended and decreasing drug release rates were found for

  6. Pharmacokinetics of vephylline--a new N-substituted theophylline derivative.

    Science.gov (United States)

    Staneva, D; Mihailova, D; Astroug, H; Prodanova, K; Micheva, M

    1988-01-01

    Vephylline (7,2-bis-2-hydroxyethylamino-1, 3-dimethylxanthine tartarate) is a xanthine derivative with high bronchodilating activity, low toxicity, and weak effects on the central nervous system. The aim of this study is to determine the pharmacokinetic parameters of vephylline after intravenous and oral (in solution and in tablets) administration to rabbits. Vephylline (dose 50 mg/kg b.w. intravenousely and orally in solution and dose 53.5 mg/kg b.w. in the form of tablets) is administered to the rabbits in an autocontrol crossover design at 7-days intervals. After the intravenous administration the distribution is relatively fast (t1/2 alpha = 3.28h). High values of the apparent volume of distribution--12.15 1/kg suggest tissue accumulation. Elimination is considerably slower (t1/2 beta = 19,00 h) than distribution. After oral administration of the drug in solution the absorption half-life is short and the bioavailability is relatively high. Peak plasma levels are attained at the first hour. The differences in the distribution and elimination patterns for vephylline and theophyline could determine a longer effect for the new bronchodilating drug. The results are discussed in regard to the future clinical application of vephylline.

  7. Simultaneous determination of theobromine, theophylline and caffeine in teas by high performance liquid chromatography

    OpenAIRE

    Adriana Barreto Alves; Neura Bragagnolo

    2002-01-01

    Para a realização deste trabalho, foram analisadas 10 amostras de diferentes tipos e marcas de chás com o objetivo de se quantificar teobromina, teofilina e cafeína simultaneamente. Para tanto, otimizou-se técnica de cromatografia líquida de alta eficiência (CLAE) baseada na ISO 10095 (1992), utilizando-se coluna Inertsil ODS-3 (150x4 mm, 5 mm), fase móvel de ácido acético 1% + acetonitrila (95:5, v/v), fluxo de 1 mL/min e detector de UV/VIS ajustado em 273 nm. Os resultados de cafeína obtido...

  8. Dgroup: DG01616 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ophylline ... D00371 ... Theophylline (JP17) ... D01712 ... Theophylline sodium acetate (JAN) ... D06103 ... Theophyllin...e (USP) ... D06104 ... Theophylline sodium glycinate (USP) ... DG01062 ... Aminophylline ... D00... DG01616 DGroup Xanthine derivative -fylline, -phylline ... DG01609 ... Xanthine-type bronchodilator ... DG01061 ... The

  9. Drug: D02017 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02017 Mixture, Drug Choline theophylline (JAN); Oxtriphylline (USP); Choline theop... Choline theophylline (JAN); Oxtriphylline (USP); Choline theophyllinate (INN) CAS: 4499-40-5 PubChem: 7849079 Drug

  10. Novel extraction and application of okra gum as a film coating agent using theophylline as a model drug

    OpenAIRE

    Ikoni J. Ogaji; Stephen W. Hoag

    2014-01-01

    The purpose of this study was to investigate the effect of extraction and application of okra gum as an aqueous film coating agent. Powdered okra pods dispersed in demineralized water was heated at 80 ± 2 o C for 30 minutes in the presence of sodium chloride. The filtrate was successively centrifuged at 4000 rpm for 30, 60, or 120 minutes and freeze dried. The samples were used as film former at different concentrations in aqueous film coating operations. Near infrared (nIR) absorption spectr...

  11. Estimation of the release profiles of multi-unit dose tablets of theophylline from the release profiles of their components

    National Research Council Canada - National Science Library

    Uhumwangho, M.U; Okor, R.S

    2008-01-01

    Purpose: The objective of this study is to investigate whether the drug release profile of a multi-unit dose form consisting of fast and slow release components can be predicted from the release profiles...

  12. Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine

    NARCIS (Netherlands)

    Zandvliet, Anthe S.; Huitema, Alwin D. R.; de Jonge, Milly E.; den Hoed, Rob; Sparidans, Rolf W.; Hendriks, Vincent M.; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

    2005-01-01

    The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine

  13. Structure-affinity relationship in the interactions of human organic anion transporter 1 with caffeine, theophylline, theobromine and their metabolites.

    Science.gov (United States)

    Sugawara, Mitsuru; Mochizuki, Takahiro; Takekuma, Yoh; Miyazaki, Katsumi

    2005-08-15

    It is well known that human organic anion transporter 1 (hOAT1) transports many kinds of drugs, endogenous compounds, and toxins. However, little is known about the structure-affinity relationship. The aim of this study was to elucidate the structure-affinity relationship using a series of structurally related compounds that interact with hOAT1. Inhibitory effects of xanthine- and uric acid-related compounds on the transport of p-aminohippuric acid were examined using CHO-K1 cells stably expressing hOAT1. The order of potency for the inhibitory effects of xanthine-related compounds on PAH uptake was 1-methyl derivative>7-methyl derivative>3-methyl derivative falling dotsxanthine>1,3,7-trimethyl derivative (caffeine). The order of potency of the inhibition was 1,3,7-trimethyluric acid>1,3-dimethyluric acid>1,7-dimethyluric acid>1-methyluric acid>uric acid. A significant correlation between inhibitory potency and lipophilicity of the tested uric acid-related compounds was observed. The main determinant of the affinity of xanthine-related compounds is the position of the methyl group. On the other hand, lipophilicity is the main determinant of the affinity of uric acid-related compounds.

  14. Enhanced elimination of theophylline, phenobarbital and strychnine from the bodies of rats and mice by squalane treatment

    National Research Council Canada - National Science Library

    Kamimura, H; Koga, N; Oguri, K; Yoshimura, H

    1992-01-01

    Our previous study suggested that squalane would be a good candidate for an antidote to reduce the toxicity of drug ingested accidentally at a high dose by enhancing the drug elimination from the body...

  15. Improved solubility and bioactivity of theophylline (a bronchodilator drug) through its new nitrate salt analysed by experimental and theoretical approaches

    Science.gov (United States)

    Mary Novena, L.; Suresh Kumar, S.; Athimoolam, S.

    2016-07-01

    Synthesis, crystal structure, vibrational spectroscopy, quantum chemical studies and biological activity of the new semi organic compound, Theophyllinium Nitrate [C7H9N4 O2)+. (NO3)-], are reported here. Crystals of Theophyllinium nitrate (TN) were grown by slow solvent evaporation technique. The crystal packing is dominated by N-H···O intermolecular hydrogen bonds. The cations and anions are aggregated almost parallel leading to a lamellar structure. This molecular aggregation features two alternate hydrogen bonded chain C22(8) and C21(6) motifs. Further, a bifurcated ring R12(4) motifs is also seen. This aggregated molecular sheets are parallel to (2 bar 06) and (20 6 bar) planes of the crystal. The solubility test is carried out to enhance the physico-chemical activity of the compound. The atomic charge distribution on different atoms of TN has been calculated by Mulliken charge analysis. A detailed interpretation of FT-IR and FT-Raman spectra of TN show that most of the bands are matching between the experimental and theoretical methods. The strong intensity bands and shifting of bands due to intermolecular hydrogen bonds are also investigated. The NBO analysis is carried out to elucidate the stability of the molecule and charge delocalization within the molecule. The HOMO-LUMO analysis reveals molecular stability and chemical reactivity of the present compound. Also, the compound was examined for its antibacterial activity and found to exhibit notable activity against Pseudomonas aeruginosa. This shows that the present compound is a good candidate for the antimicrobial agent apart from its inherent Bronchodilator drug property. Hence, the new compound (TN) may be a good alternative for patients with Chronic Obstructive Pulmonary Disease (COPD) and bacterial infections.

  16. Drug: D10297 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10297 Mixture ... Drug Theophylline - dextrose mixt; Theophylline in dextrose (TN) (Theophylline... [DR:D00371] | Theophylline [DR:D06103]), Dextrose [DR:D02325] ... ATC code: R03DA54 ... Treatment of bronchitis ... PubChem: 163312328 ...

  17. Theophylline-Based KMUP-1 Improves Steatohepatitis via MMP-9/IL-10 and Lipolysis via HSL/p-HSL in Obese Mice

    Directory of Open Access Journals (Sweden)

    Bin-Nan Wu

    2016-08-01

    Full Text Available KMUP-1 (7-[2-[4-(2-chlorobenzenepiperazinyl]ethyl]-1,3-dimethylxanthine has been reported to cause hepatic fat loss. However, the action mechanisms of KMUP-1 in obesity-induced steatohepatitis remains unclear. This study elucidated the steatohepatitis via matrix metallopeptidase 9 (MMP-9 and tumor necrosis factor α (TNFα, and related lipolysis via hormone sensitive lipase (HSL and adipose triglyceride lipase (ATGL by KMUP-1. KMUP-1 on steatohepatitis-associated HSL/p-HSL/ATGL/MMP-9/TNFα/interleukin-10 (IL-10 and infiltration of M1/M2 macrophages in obese mice were examined. KMUP-1 was administered by oral gavage from weeks 1–14 in high-fat diet (HFD-supplemented C57BL/6J male mice (protection group and from weeks 8–14, for 6 weeks, in HFD-induced obese mice (treatment group. Immunohistochemistry (IHC and hematoxylin and eosin (H&E staining of tissues, oil globules number and size, infiltration and switching of M1/M2 macrophages were measured to determine the effects on livers. IL-10 and MMP-9 proteins were explored to determine the effects of KMUP-1 on M1/M2 macrophage polarization in HFD-induced steatohepatitis. Long-term administration of KMUP-1 reversed HFD-fed mice increased in body weight, sGOT/sGPT, triglyceride (TG and glucose. Additionally, KMUP-1 decreased MMP-9 and reactive oxygen species (ROS, and increased HSL/p-HSL and IL-10 in HFD mice livers. In conclusion, KMUP-1, a phosphodiesterase inhibitor (PDEI, was shown to reduce lipid accumulation in liver tissues, suggesting that it could be able to prevent or treat steatohepatitis induced by HFD.

  18. Multifocal atrial tachycardia

    Science.gov (United States)

    ... the last 6 weeks Overdosed on the drug theophylline Sepsis When the heart rate is less than ... potassium through a vein Stopping medicines, such as theophylline, which can increase heart rate Taking medicines to ...

  19. A New Application of Lipid Nanoemulsions as Coating Agent, Providing Zero-Order Hydrophilic Drug Release from Tablets

    Directory of Open Access Journals (Sweden)

    Nicolas Anton

    2012-01-01

    Full Text Available The objective of the present investigation was to evaluate potential of nanoemulsions as a coating material for the tablets. The nanoemulsion of size less than 100 nm was prepared using a simple and low-energy spontaneous emulsification method. Conventional tablets containing theophylline as a model hydrophilic drug were prepared. The theophylline tablets were coated with the nanoemulsion using a fluid bed coater. The effect of different levels of the nanoemulsion coating on the theophylline release was evaluated. The theophylline tablets containing different levels of the nanoemulsion coating could be successfully prepared. Interestingly, the coating of tablet with the nanoemulsion resulted in zero-order release of theophylline from the tablets. The noncoated theophylline tablets release the entire drug in less than 2 minutes, whereas nanoemulsion coating delayed the release of theophylline from tablets. This investigation establishes the proof of concept for the potential of nanoemulsions as a coating material for tablets.

  20. Spray Drying of Cocrystals for Engineering Particle Properties : Diploma Work

    OpenAIRE

    Hadi, Kuther

    2015-01-01

    The goals of this work were to combine crystal and particle engineering in a single step using spray drying and improve particle properties that can potentially minimize the need for coating agents. Specific aim was to prepare and characterize theophylline cocrystal particles intended for inhalation using by spray drying. Theophylline is a bronchodilator used in the treatment of asthma and is used as a model drug in this study. Theophylline cocrystals with citric acid, flufenamic acid and sac...

  1. Evaluación de las subpoblaciones de linfocitos T en pacientes tuberculosos empleand la modulación con teofilina T lymphocyte subsets evaluation in patients with pulmonary tuberculosis using theophylline modulation

    Directory of Open Access Journals (Sweden)

    Diana Dlugovitzky

    1991-04-01

    Full Text Available Se evaluaron las poblaciones y subpoblaciones linfocitarias en pacientes con tuberculosis pulmonar antes y durante la terapia relacionando estos valores con la incidencia y evolución de la enfermedad. Pacientes en sus diversas manifestaciones clínicas, vírgenes de tratamiento, se estudiaron por baciloscopía (BAAR, radiología, i.d.r. Mantoux y análisis complementarios. Se cuantificaron mediante la prueba de Rosetas espontáneas (RE linfocitos T totales y activos (RE a 4ºC y 37ºC, T colaboradores (RE Teofilina Resistentes: RETR y supresores (RE Teofilina Sensibles: RETS. Los exámenes se repitieron en los mismos sujetos iniciado el tratamiento y en testigos sanos (TS. Se demostró en los pacientes en todas sus formas clínicas un descenso significativo en los valores relativos y absolutos de células T y en la relación RETR/RETS (menor de 1. Existe asociación entre la forma clínica y el número de linfocitos T colaboradores. Los pacientes en tratamiento con evolución favorable, evidenciaron un incremento significativo en los linfocitos T totales, activos, colaboradores y en la relación RETR/RETS. Los enfermos con baciloscopía altamente positiva presentaron i.d.r. Mantoux baja o negativa y marcado descenso de células inmunocompetentes. Se comprobó asociación entre estas tres variables, lo mismo que entre el estado nutricional y la predisposición a contraer la enfermedad.T cells and T cells subsets in peripheral blood of patients with different forms of pulmonary tuberculosis were evaluated to explain some aspects of the immunocompromised state of these subjects. Diagnosis was made by baciloscopy (BAAR, chest roentgenography i.d.r Mantoux, and other clinical analysis. Spontaneous E-Rosette test (RE was used to quantify Total (RET 4ºC and Active T cells (REA 37ºC and the same test after incubation with Theophilline (The for helper cells (The-re-sistant cells: RETR and suppressor cells (The-sensitive cells: RETS. Patients were followed for at least 4 months after therapy. The data demonstrate a significant decrease of relative and absolute numbers of Total T-cells and a diminished T helper/T suppressor subset ratio (RETR/RETS which dropped to less than 1 in untreated patients. Treated patients with a favourable evolution showed a restoration of Total active and helper T cells. RETR/RETS ratio was also significantly increased. In patients with highly positive BAAR, low on negative i.d.r Mantoux, a decreased level of immunocompetent cells was observed. The 3 aspects were associated. Nutritional condition of the patients wal also associated with the predisposition to acquire this disease.

  2. An evaluative study of the short-term effects of oncedaily, sustained ...

    African Journals Online (AJOL)

    To examine the effects of once-daily, sustainedrelease theophylline on sleep patterns in nocturnal asthmatics. Design. Double-blind, randomised, cross-over, placebocontrolled trial over 22 days. Seven-day period to establish therapeutic levels of theophylline (11.8 ± 3 mg/I); a-day cross-over period of 4 days' placebo or ...

  3. Caffeine Content of Tea and Coffee

    African Journals Online (AJOL)

    1974-03-13

    Mar 13, 1974 ... The xanthines (caffeine, theophylline, and theobromine) occur in plants widely distributed throughout the world. Best known for the preparation of beverages are coffee beans which contain caffeine, tea leaves which contain caffeine and theophylline, and cocoa seeds which contain caffeine and ...

  4. Optimization and Development of Swellable Controlled Porosity ...

    African Journals Online (AJOL)

    Erah

    (Aerospace, China) and mean thickness was calculated. Assay of theophylline. The theophylline content of each tablet formulation was analyzed spectrophoto- metrically (Shimadzu UV-1601) at 271 nm based on the crushed material from 5 randomly selected tablets from each batch. The tablet material was dissolved in 0.1 ...

  5. Drug Release Mechanism of Slightly Soluble Drug from ...

    African Journals Online (AJOL)

    theophylline) from nanocomposite of zeolite (ZLT) or hydrotalcite (HTC) used as drug carrier. Methods: Nanocomposite was prepared with dispersion of either ZLT or HTC as drug carrier and theophylline (THP) as drug in drug to clay ratios of 1:2 ...

  6. Drug: D00227 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00227 Drug Aminophylline (USP/INN); Somophyllin (TN); Theophylline ethylenediamin...vative Bonding agent of Theophylline [DR:D00371] and Ethylenediamine [DR:D01114] ...hodilator Cyp substrate ... DG01892 ... CYP1A2 substrate ATC code: R03DA05 Chemical group: DG01062 ... Xanthine deri

  7. The relationship between energy metabolism and the action of inhibitors of histamine release

    DEFF Research Database (Denmark)

    Garland, L G; Johansen, Torben

    1977-01-01

    1 Dextran-induced release of histamine from rat mast cells was inhibited equally in complete and glucose-free Tyrode solution by doxantrazole (0.03-3 micronmol/l), theophylline (0.1-3 mmol/l) and dicumarol (0.01-10 micronmol/litre). 2 Doxantrazole (3 micronmol/l), theophylline (3 mmol....... 4 These results suggest that dicumarol, like doxantrazole and theophylline, inhibits histamine release without affecting mast cell energy metabolism. In contrast, papaverine probably inhibits release by depleting ATP that is required for exocytosis. 5 Inhibition of histamine release by dibutyryl...

  8. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells

    NARCIS (Netherlands)

    Endres, S; Fülle, H J; Sinha, B; Stoll, D; Dinarello, C A; Gerzer, R; Weber, P.C.

    Recent reports have shown that phosphodiesterase (PDE) inhibitors suppress production of tumour necrosis factor-alpha (TNF-alpha) in mouse macrophages. In the present study we show that theophylline, pentoxifylline and 3-isobutyl-1-methylxanthine markedly suppress the lipopolysaccharide

  9. Oxcarbazepine

    Science.gov (United States)

    ... Depakote); proton-pump inhibitors such as lansoprazole (Prevacid), omeprazole (Prilosec), and pantoprazole (Protonix); theophylline (Theo-Dur); and ... are pregnant, plan to become pregnant, or are breastfeeding. If you are using hormonal contraceptives, you should ...

  10. References

    African Journals Online (AJOL)

    STG's) and. Essential Drug List (EDL) in 1996 some of the traditional medication for the treatment of asthma and chronic obstructive pulmonary disease (COPD) were removed from the medication list. e.g. slow release oral theophylline.

  11. Chronic obstructive airway diseases: Is the EDL sufficient? A study ...

    African Journals Online (AJOL)

    STG's) and Essential Drug List (EDL) in 1996 some of the traditional medication for the treatment of asthma and chronic obstructive pulmonary disease (COPD) were removed from the medication list, e.g. slow release oral theophylline.

  12. Therapeutic Drug Monitoring

    Science.gov (United States)

    ... LDL Particle Testing (LDL-P) Lead Legionella Testing Leptin Levetiracetam Lipase Lipid Profile Lipoprotein (a) Lithium Liver ... Bronchodilators Theophylline , caffeine Asthma , chronic obstructive pulmonary disorder (COPD) , neonatal apnea ... tacrolimus , sirolimus , mycophenolate mofetil , ...

  13. Aminophylline overdose

    Science.gov (United States)

    ... are found in medicines with these names (with brand names in parentheses): Aminophylline Theophylline (Theo-Dur, Slo- ... AND JOINTS Muscle twitching and cramping NERVOUS SYSTEM Confusion Convulsions Dizziness Fever Hallucinations (thinking something is there, ...

  14. Environ: E00771 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00771 Guarana Medicinal herb Caffeine [CPD:C07481], Theophylline [CPD:C07130], The...obromine [CPD:C07480], Tannin, Saponin Paullinia cupana [TAX:392747] Sapindaceae Guarana seed Major component: Caffeine

  15. Radioimmunoassays for cyclic AMP cross-react with phosphodiesterase inhibitors and buffer components

    NARCIS (Netherlands)

    Sinha, B; Semmler, J; Haen, E; Moeller, J; Endres, S

    We addressed the issue of cross-reactivity of several commonly used phosphodiesterase inhibitors with radioimmunoassays for cyclic AMP, after we had observed a considerably high cross-reactivity with a noncommercial antibody. Theophylline, pentoxifylline, penthydroxifylline (BL 194), albifylline

  16. Cetirizine

    Science.gov (United States)

    ... to pollen, dust, or other substances in the air) and allergy to other substances (such as dust ... other medications for cold and allergy, sedatives, sleeping pills, tranquilizers, and theophylline (Theo-24, Theolair). Your doctor ...

  17. [Auto-intoxication with an illegal slimming product].

    Science.gov (United States)

    Kraaijenbrink, Bastiaan V C; van den Hoek, Hester L; Nowitzky, Ralph J M; Wilms, Erik B

    2015-01-01

    Dexaprine is an illegal slimming product with known serious adverse cardiac effects. Despite warnings from the Netherlands Food and Consumer Product Safety Authority, Dexaprine is still readily available online. A 29-year-old woman was brought into the emergency room after a suicide attempt with 29 Dexaprine tablets. The symptoms on admission were agitation, nausea and vomiting, hypotension, atrioventricular nodal reentrant tachycardia and hypothermia. Extensive drug screening revealed that Dexaprine contains caffeine, amphetamine and theophylline, explaining the symptoms. The patient was admitted to the intensive care unit for supportive therapy overnight before being discharged. In contrast to the advertised composition, Dexaprine contains several pharmacologically active substances including caffeine, amphetamine and theophylline. In intoxications caused by products of unknown composition, additional toxicological screening is invaluable to determine the extent and severity of intoxication. In this case, the patient's symptoms were due to theophylline intoxication. Ultimately, the theophylline levels did not indicate additional treatment such as haemodialysis.

  18. 77 FR 35691 - Notice of Withdrawal of Certain Unapproved Abbreviated New Drug Applications

    Science.gov (United States)

    2012-06-14

    ... maleate. 83421 Probenecid. 83439 Quinidine sulfate. 83444 Rauwolfia serpentina. 83454 Lidocaine. 83494...; phenacetin; caffeine. 85442 Chlordiazepoxide hydrochloride. 85489 Probenecid. 85516 Theophylline. 85576.... 86991 Probenecid. 86999 Butalbital; aspirin; phenacetin; caffeine. 87000 Hydralazine hydrochloride...

  19. Hops

    Science.gov (United States)

    ... by mouth for medicinal uses. Special precautions & warnings: Pregnancy and breast-feeding: There is not enough reliable ... that are changed by the liver include theophylline, omeprazole, clozapine, progesterone, lansoprazole, flutamide, oxaliplatin, erlotinib, and caffeine. ...

  20. Extraction of purine alkaloids from maté (Ilex paraguariensis) using supercritical CO(2).

    Science.gov (United States)

    Saldaña, M D; Mohamed, R S; Baer, M G; Mazzafera, P

    1999-09-01

    Experimental data for the supercritical CO(2) extraction of purine alkaloids (caffeine, theobromine, and theophylline) from ground herbal maté tea (Ilex paraguaryensis) using a high-pressure apparatus are presented. Caffeine, theophylline, and theobromine were identified in the extracted fractions using HPLC. Results indicated a much higher CO(2) selectivity for caffeine in comparison with those for theophylline and theobromine. Solubilities of pure compounds in carbon dioxide were also determined at 313.2, 323.2, 338.2, and 343.2 K, and pressures ranging from 14 to 24 MPa. Caffeine solubility exhibited a retrograde behavior with temperature while theophylline and theobromine manifested a normal behavior at conditions explored in this study. Solubilities in binary CO(2)/purine alkaloid model systems were much higher than those obtained during extraction of maté tea, demonstrating the difficulty of using binary data in predicting complex multicomponent behavior.

  1. Pentoxifylline

    Science.gov (United States)

    ... to caffeine-containing products (coffee, tea, colas), pentoxifylline, theobromine, theophylline (Theo-Dur), or any other drugs.tell ... of reach of children. Store it at room temperature and away from excess heat and moisture (not ...

  2. Relation of 24-hour urinary caffeine and caffeine metabolite excretions with self-reported consumption of coffee and other caffeinated beverages in the general population

    National Research Council Canada - National Science Library

    Petrovic, Dusan; Estoppey Younes, Sandrine; Pruijm, Menno; Ponte, Belén; Ackermann, Daniel; Ehret, Georg; Ansermot, Nicolas; Mohaupt, Markus; Paccaud, Fred; Vogt, Bruno; Pechère-Bertschi, Antoinette; Martin, Pierre-Yves; Burnier, Michel; Eap, Chin B; Bochud, Murielle; Guessous, Idris

    2016-01-01

    ...% of caffeine is provided by caffeinated coffee consumption, and then metabolized by the liver CYP1A2 enzyme into paraxanthine (~80%), theobromine (~12%) and theophylline (~4%) [4]. Caffeine and caffeine rel...

  3. PREPARATION, CHARACTERIZATION AND APPLICATION OF LINEAR DEXTRINS .6. GENERAL APPLICABILITY AND MECHANISM OF PROGRAMMED RELEASE FROM AMYLODEXTRIN TABLETS

    NARCIS (Netherlands)

    TEWIERIK, GHP; VANDERVEEN, J; EISSENS, AC; LERK, CF

    1993-01-01

    This study reports the successful application of amylodextrin as a unique excipient in the design of programmed release systems. Physical mixtures of amylodextrin with the model compounds theophylline, paracetamol, methyl-PABA, prednisolone, atrazine, procaine HCl and potassium dichromate,

  4. IR and ESR studies on novel Cu(II) theophyllinato complexes containing mono- or bidentate ligands

    Science.gov (United States)

    Forizs, Edit; David, L.; Cozar, O.; Chiş, V.; Damian, G.; Csibi, Jolán

    1999-05-01

    Three mixed-ligand copper(II) complexes containing theophylline and mono- or bidentate N-donor ligands (2,2'-bipyridine, 4-fluoraniline and 1,10-phenanthroline) were synthesized and characterized by elemental analysis, IR and ESR spectra. According to IR and ESR data the Cu(II) complexes exhibit a distorted tetrahedral coordination of copper by two nitrogen atoms of the monodentate or bidentate ligands and the two monodentate theophyllinate anion bonded through N(7) atom.

  5. Metabolism of alkaloids in coffee plants

    OpenAIRE

    ASHIHARA, Hiroshi

    2006-01-01

    Coffee beans contain two types of alkaloids, caffeine and trigonelline, as major components. This review describes the distribution and metabolism of these compounds. Caffeine is synthesised from xanthosine derived from purine nucleotides. The major biosynthetic route is xanthosine -> 7-methylxanthosine -> 7-methylxanthine -> theobromine -> caffeine. Degradation activity of caffeine in coffee plants is very low, but catabolism of theophylline is always present. Theophylline is converted to xa...

  6. Long-term effect of pH on B-cell function in isolated islets of Langerhans in tissue culture

    DEFF Research Database (Denmark)

    Brunstedt, J; Nielsen, Jens Høiriis

    1978-01-01

    Collagenase isolated mouse pancreatic islets were maintained in tissue culture for up to 5 months in a culture medium buffered with Hepes and the pH varying between 6.8 and 7.6. The amount of insulin released into the medium and the insulin response to glucose and glucose plus theophylline were...... glucose and glucose plus theophylline than islets cultured at the other pH values, but later they lost their insulin releasing ability....

  7. Radio-immunoassay of somatostatin from isolated rat pancreatic islets

    Energy Technology Data Exchange (ETDEWEB)

    Vonen, B.; Florholmen, J.; Giaever, A.K.; Burhol, P. (Tromsoe Univ. (Norway))

    1989-04-01

    Certain aspects of radio-immunoassay of somatostatin from isolated rat pancreatic islets are described. Somatostatin-14, and not somatostatin-28, is secreted from isolated rat pancreatic islets. Less somatostatin secretion is measured per islet owing to purity of tracer in the radio-immunoassay. Theophylline apparently cross-reacts with somatostatin in the assay described, and this has to be taken into consideration when studying somatostatin release induced by theophylline in isolated islets. (author).

  8. The Differences in the Relaxant Effects of Different Fractions of Rosa damascena on Guinea Pig Tracheal Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Hassan Rakhshandah

    2010-06-01

    Full Text Available Objective(sIn the present study, the differences in the relaxant effects of aqueous, ethyl acetate and n-butanol fractions of Rosa damascena on tracheal smooth muscle of guinea pigs were examined. Materials and MethodsThe relaxant effects of three cumulative concentrations of each fraction (0.1, 0.2 and 0.4 g% in comparison with saline and three cumulative concentrations of theophylline (0.1, 0.2, and 0.4 mM were examined on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1, n= 5 and 10 µM methacholine (group 2, n= 8. ResultsIn group 1, all concentrations of theophylline, ethyl acetate fraction and two final concentrations of n-butanol fraction showed significant relaxant effects in comparison with saline (p< 0.05 to P< 0.001. In group 2, all concentrations of theophylline, ethyl acetate and aqueous fractions showed concentration dependent relaxant effects compared to that of saline (p< 0.01 to P< 0.001. In addition, the effect of ethyl acetate fraction in group 1 was significantly higher than those of theophylline (p< 0.05 to p< 0.001. However, the effects of other fractions were significantly lower than theophylline in both groups (p< 0.01 to p< 0.001. There were significant correlations between the relaxant effects and concentrations for theophylline and all fractions (except aqueous fractions in group 1 in both groups. ConclusionThe results showed a potent relaxant effect for ethyl acetate fraction of R. damascena on tracheal smooth muscle comparable to that of theophylline but a relatively weak relaxant effect for aqueous and n-butanol fractions at concentrations used.

  9. Contribution of adenosine to the increase in skeletal muscle blood flow caused by manual acupuncture in rats.

    Science.gov (United States)

    Shinbara, Hisashi; Nagaoka, Satomi; Izutani, Yasuyuki; Okubo, Masamichi; Kimura, Keisaku; Mizunuma, Kunio; Sumiya, Eiji

    2017-08-01

    Adenosine is believed to play an important role in local acupuncture analgesia. The aim of this study was to investigate the contribution of adenosine to the increase in skeletal muscle blood flow (MBF) caused by manual acupuncture (MA). Thirty-two male Sprague-Dawley rats (310-360 g) were anaesthetised and divided into four equal groups (n=8 each): Saline, Saline+MA, Theophylline, and Theophylline+MA. In the two MA groups, the sparrow-pecking MA technique was applied at 30 repetitions per min for 1 min to a depth of 15-18 mm using a stainless steel acupuncture needle (0.20×40 mm). The stimulus point was located on the right tibialis anterior (TA) muscle 7-8 mm below the knee. Animals in the two theophylline groups were intra-arterially injected with 8-(p-sulphophenyl) theophylline, a non-selective adenosine receptor antagonist, at a dose of 30 mg/kg before MA. Animals in the two saline groups received control saline. Fluorescent microspheres (15 µm in diameter, yellow-green fluorescent) were used for MBF measurement in all four groups. MA of the TA muscle significantly increased MBF (Saline+MA vs Saline: p=0.001; Saline+MA vs Theophylline: p=0.008). Pre-treatment with theophylline appeared to inhibit this increase (Theophylline vs Theophylline+MA; p=1.000). MBF in the Theophylline+MA group was 43% lower than in the Saline+MA group, although this was not significantly different (p=0.104). The results suggest that adenosine leads to an increase in MBF caused by MA. Adenosine may play a role in acupuncture analgesia by washing out algesic substances. Further studies are needed in order to elucidate the precise mechanism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Type I photosensitized reactions of oxopurines. Kinetics and thermodynamics of the reaction with triplet benzophenone by time-resolved photoacoustic spectroscopy

    Science.gov (United States)

    Murgida, Daniel H.; Erra Balsells, Rosa; Crippa, Pier Raimondo; Viappiani, Cristiano

    1998-09-01

    Benzophenone photosensitized reactions of caffeine, theophylline and theobromine were investigated in acetonitrile by time-resolved laser-induced photoacoustics. In the three cases global quenching rate constants of triplet benzophenone were measured as a function of temperature and it was observed that this is a non-activated process. Besides, for theobromine and theophylline heats for NH hydrogen abstraction reactions were determined. In agreement with semiempirical calculation predictions, hydrogen abstraction is thermodynamically more favorable and faster for theophylline (Δ H=-265 kJ mol -1, kr=9.6×10 8 M -1 s -1) than for theobromine (Δ H=-168 kJ mol -1, kr=3.7×10 8 M -1 s -1).

  11. Characterization of polymorphic solid-state changes using variable temperature X-ray powder diffraction

    DEFF Research Database (Denmark)

    Karjalainen, Milja; Airaksinen, Sari; Rantanen, Jukka

    2005-01-01

    The aim of this study was to use variable temperature X-ray powder diffraction (VT-XRPD) to understand the solid-state changes in the pharmaceutical materials during heating. The model compounds studied were sulfathiazole, theophylline and nitrofurantoin. This study showed that the polymorph form...... of sulfathiazole SUTHAZ01 was very stable and SUTHAZ02 changed as a function of temperature to SUTHAZ01. Theophylline monohydrate changed via its metastable form to its anhydrous form during heating and nitrofurantoin monohydrate changed via amorphous form to its anhydrous form during heating. The crystallinity...... of SUTHAZ01, SUTHAZ02 and theophylline monohydrate were very high and stable. Nitrofurantoin monohydrate was also very crystalline at room temperature but during heating at lower temperatures the crystallinity decreased and started to increase strongly at the temperature where the sample had changed...

  12. Fractal analysis of SEM images and mercury intrusion porosimetry data for the microstructural characterization of microcrystalline cellulose-based pellets

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Carracedo, A.; Alvarez-Lorenzo, C.; Coca, R.; Martinez-Pacheco, R.; Concheiro, A. [Departamento de Farmacia y Tecnologia Farmaceutica, Universidad de Santiago de Compostela, Santiago de Compostela 15782 (Spain); Gomez-Amoza, J.L. [Departamento de Farmacia y Tecnologia Farmaceutica, Universidad de Santiago de Compostela, Santiago de Compostela 15782 (Spain)], E-mail: joseluis.gomez.amoza@usc.es

    2009-01-15

    The microstructure of theophylline pellets prepared from microcrystalline cellulose, carbopol and dicalcium phosphate dihydrate, according to a mixture design, was characterized using textural analysis of gray-level scanning electron microscopy (SEM) images and thermodynamic analysis of the cumulative pore volume distribution obtained by mercury intrusion porosimetry. Surface roughness evaluated in terms of gray-level non-uniformity and fractal dimension of pellet surface depended on agglomeration phenomena during extrusion/spheronization. Pores at the surface, mainly 1-15 {mu}m in diameter, determined both the mechanism and the rate of theophylline release, and a strong negative correlation between the fractal geometry and the b parameter of the Weibull function was found for pellets containing >60% carbopol. Theophylline mean dissolution time from these pellets was about two to four times greater. Textural analysis of SEM micrographs and fractal analysis of mercury intrusion data are complementary techniques that enable complete characterization of multiparticulate drug dosage forms.

  13. Idiopathic Systemic Capillary Leak Syndrome: A Diagnostic Challenge and Its Management

    Directory of Open Access Journals (Sweden)

    Janak Tarun Bahirwani

    2017-10-01

    Full Text Available Idiopathic Systemic Capillary Leak Syndrome (ISCLS is a fatal disorder characterised by recurrent episodes of hypotension, hypoalbuminemia and haemoconcentration. It is a rare disease, under-reported partly because of unawareness of treating physician. Here is a description of a 30 year old male presenting with history of fever, generalized oedema progressing to hypovolemic shock and multi organ dysfunction. His laboratory studies showed haemoconcentration, hypoalbuminemia and monoclonal gammopathy with negative bacteriological cultures. After excluding other probable etiologies he was diagnosed to have ISCLS. He was managed successfully with intravenous methylprednisolone, theophylline and other supportive measures. He has been put on prophylactic oral theophylline for one year.

  14. Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets

    DEFF Research Database (Denmark)

    Fonteyne, Margot; Wickström, Henrika; Peeters, Elisabeth

    2014-01-01

    quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline......-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect...... their processability and several critical quality attributes of the resulting granules and tablets....

  15. Dehydration studies using a novel multichamber microscale fluid bed dryer with in-line near-infrared measurement

    DEFF Research Database (Denmark)

    Räsänen, Eetu; Rantanen, Jukka; Mannermaa, Jukka-Pekka

    2003-01-01

    . The materials studied were disodium hydrogen phosphates with three different levels of hydrate water and wet theophylline granules. Measured process parameters of fluid bed drying were logged, including in-line NIR signals. Off-line analyses consisted of X-ray powder diffraction patterns, Fourier transform NIR...... of solid materials. The temperature and the moisture content of the process air were demonstrated to be significant factors for the solid-state stability of theophylline. The presented setup is a material and cost-saving approach for studying the influence of different process parameters on dehydration...

  16. (Diethylenetriaminebis(theophyllinatozinc(II dihydrate

    Directory of Open Access Journals (Sweden)

    Attila-Zsolt Kun

    2009-05-01

    Full Text Available In the title compound, [Zn(C7H7N4O22(C4H13N3]·2H2O, the ZnII ion is pentacoordinated by three N atoms of the diethylenetriamine ligand and one N atom of each of the two theophyllinate anions in a distorted trigonal-bipyramidal geometry. The Zn—N distances range from 2.076 (3 to 2.221 (3 Å. The crystal packing is stabilized by O—H...O, O—H...N and N—H...O hydrogen bonds involving the theophylline and diethylenetriamine ligands and uncoordinated water molecules.

  17. Dissociation between insulin secretion and DNA synthesis in cultured pancreatic islets

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1985-01-01

    Glucose has been suggested to be the most important stimulus for beta cell replication in vivo and in vitro. In order to study the relationship between insulin secretion and DNA synthesis, newborn rat islets were cultured in the presence of different concentrations of glucose, theophylline and 3......M glucose in spite of a dose dependent increase in insulin release. 5 mM theophylline potentiated the glucose induced insulin release but lowered both 3H-Tdr synthesis and insulin content in the islets. In contrast, 0.05 mM IBMX induced a significant stimulation of both insulin release and 3H...

  18. State of T-lymphocytes at different stages of anthracosis

    Energy Technology Data Exchange (ETDEWEB)

    Tlegenova, A.N.; Baimanova, A.M. (Institut Fiziologii i Gigieny Truda AN Kazakhskoi SSR, Karaganda (USSR))

    1990-04-01

    Recommends analysis of T-rosette formation in blood samples as a method of diagnosing anthracosis in its early stages in coal miners. Tests were performed on a total of 134 miners aged 38-49, with at least 10 years employment in coal mining. Particularly indicative of developing anthracosis was the ratio of theophylline resistant to theophylline sensitive T-lymphocytes, which increased in sufferers in comparison with the control (although the overall number of T-lymphocytes showed little change). When the anthracosis was complicated by chronic bronchitis, this ratio decreased, with an overall fall in numbers of all T-lymphocytes. 7 refs.

  19. Effects of quinoa hull meal on piglet performance and intestinal epithelial physiology

    DEFF Research Database (Denmark)

    Carlson, Dorthe; Fernandez, J.A.; Poulsen, H.D.

    2012-01-01

    added. Epithelial permeability, Na+-dependent glucose transport and serotonin (5-HT) and theophylline- induced secretion were measured. The results showed that QHM had no influence on piglet’s growth (p = 0.41) or feed intake (p = 0.17). In spite of a large difference in saponin content between SA...... that consumed 100 or 300 mg/kg SA-QHM. The secretory response to 5-HT was not affected (p = 0.59) by dietary treatments, but the theophylline-induced secretion decreased (p = 0.02) with increasing dietary SA-QHM. The changes in epithelial physiology mea...

  20. CPD

    African Journals Online (AJOL)

    croinoglycate) or unacceptable side- effects (theophyllines and SIT). Their use cannot be justified under any circumstances. In addition the value of alternative and complementary thera- pies, such as homeopathy, acupuncture, herbal medicine and chiropractic manipulation are either not researched or lacking, in eft'ieacy.

  1. Relaxant effect of Thymus vulgaris on guinea-pig tracheal chains and its possible mechanism(s).

    Science.gov (United States)

    Boskabady, M H; Aslani, M R; Kiani, S

    2006-01-01

    Thymus vulgaris for the treatment of respiratory diseases is indicated widely, and relaxant effects on smooth muscle have been shown previously. In the present study, the relaxant effects of macerated and aqueous extracts of Thymus vulgaris on tracheal chains of guinea-pigs were examined using cumulative concentrations of macerated and aqueous extracts in comparison with saline (as the negative control) and theophylline (as the positive control). The relaxant effects of four cumulative concentrations of macerated and aqueous extracts (0.25, 0.5, 0.75 and 1.0 g %) in comparison with saline (as the negative control) and four cumulative concentrations of theophylline (0.25, 0.5, 0.75 and 1.0 mm; as the positive control) were examined for their relaxant effects on precontracted tracheal chains of guinea-pig by 60 mm KCl and 10 microm methacholine in two different conditions: non-incubated tissues and incubated tissues with 1 microm propranolol and 1 microm chlorphenamine. There were significant correlations between the relaxant effects and the concentrations for both extracts and theophylline in all experimental groups (p Thymus vulgaris on guinea-pig tracheal chains that was comparable to theophylline at the concentrations used. Copyright 2006 John Wiley & Sons, Ltd.

  2. Author Details

    African Journals Online (AJOL)

    Uhumwangho, MU. Vol 7, No 2 (2008) - Articles Estimation of the release profiles of multi-unit dose tablets of theophylline from the release profiles of their components. Abstract PDF · Vol 10, No 5 (2011) - Articles Development of an Optimised Losartan Potassium Press-Coated Tablets for Chronotherapeutic Drug Delivery

  3. Synthesis and Swelling Behavior of pH-Sensitive Semi-IPN Superabsorbent Hydrogels Based on Poly(acrylic acid) Reinforced with Cellulose Nanocrystals

    National Research Council Canada - National Science Library

    Lim Sze Lim; Noor Afizah Rosli; Ishak Ahmad; Azwan Mat Lazim; Mohd Cairul Iqbal Mohd

    2017-01-01

    .... It was found that the hydrogel reached maximum swelling at pH 7. The potential of the resulting hydrogels to act as drug carriers was then evaluated by means of the drug encapsulation efficiency test using theophylline as a model drug. It was observed that 15% CNC/PAA hydrogel showed the potential to be used as drug carrier system.

  4. JI1II

    African Journals Online (AJOL)

    hazardous side-effects such as theophylline, digoxin, cyclo- sporin, lithium or ... blocked one. In many cases, the foreign body will pop Out with minimal trauma. Simple, but often forgotten. . The other minor point concerns cauterising Little's area for recurrent .... lation that should limit the future success of the industry.

  5. Author Details

    African Journals Online (AJOL)

    Preparation, Characterization and In vitro Evaluation of Theophylline Nanoparticles Prepared with Dextran- Conjugated Soy Protein Abstract PDF · Vol 14, No 5 (2015) - Articles Headspace Solid-Phase Microextraction Coupled with Gas Chromatography-Mass Spectrometric Analysis of Volatile Components of Raw and ...

  6. The cardiovascular effects of methylxanthines

    NARCIS (Netherlands)

    Riksen, N.P.; Smits, P.; Rongen, G.A.P.J.M.

    2011-01-01

    In the concentration range that is normally achieved in humans, e.g., after the drinking of coffee or in patients treated with theophylline, the cardiovascular effects of methylxanthines are primarily due to antagonism of adenosine A(1) and A(2) receptors. Inhibition of phosphodiesterases or

  7. Glaucoma: a brief update for 2017

    African Journals Online (AJOL)

    anticholinergic effect. Methylxanthines (e.g. theophylline and caffeine (low risk)). The methylxanthines may precipitate an attack of angle-closure glaucoma, by accentuating the anti-cholinergic action on the eye. .... may elicit both local and systemic adverse effects, with the latter warranting similar precautions to those that ...

  8. BKR 26(2) pp. 36-42 (Igunnu)

    African Journals Online (AJOL)

    Femi Olorunniji

    2014-06-30

    Jun 30, 2014 ... AP is inhibited by several compounds on the basis of different mechanisms. L- phenylalanine, imidazole, histamine and theophylline are known to inhibit alkaline phosphatase uncompetitively while phosphate, phosphoethanolamine and phenylphosphonate are competitive inhibitors (Ghosh and Fishman, ...

  9. Effect of curing time on ph and time dependant coated pellets ...

    African Journals Online (AJOL)

    METHODS: Theophylline loaded pellets were coated with a non aqueous time and pH dependant eudragit solution. The coated pellets were cured at constant process parameters (45°C) for different time periods (05, 10, or 20 min) and the drug release profile and other characteristics of formulation were evaluated.

  10. In-vitro Characterization of Optimized Multi-Unit Dosage Forms of ...

    African Journals Online (AJOL)

    Michael Horsfall

    In-vitro Characterization of Optimized Multi-Unit Dosage Forms of Theophylline and its Solid State Characterisation. *1UHUMWANGHO, M U; 2RAMANA, MURTHY K V. 1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Benin, Nigeria. 2University College of Pharmaceutical ...

  11. Effect of Coating Solvent Ratio on the Drug Release Lag Time of ...

    African Journals Online (AJOL)

    Erah

    Methods: Porous theophylline osmotic pump tablets were formulated by direct compression and coated by spraying with varying ratios of water-alcohol containing hydroxypropyl methylcellulose (HPMC, 5 cps) as primary swelling layer and Eudragit® RSPO and RLPO as porous layer. The viscosity of HPMC coating solution ...

  12. Download this PDF file

    African Journals Online (AJOL)

    be treated with ipratropium and low dosage beta 2 agonists to decrease the side effects of beta 2 agonists. 4'9 The routine use of inhalation steroids in. COPD is uncertain, but more useful in patiens with an allergic background.'°'. This is also the same as in the STG and EDL. The use of long acting oral theophylline.

  13. Validation of Individual Non-Linear Predictive Pharmacokinetic ...

    African Journals Online (AJOL)

    B. Testosterone metabolism in rat brain is differentially enhanced by phenytoin inducible cytochrome. P450 isoforms. Journal of. Neuroendocrinology 1999; 11: 597-604. 20. Saitoh T, Kokue E, Shimoda M. The impact of acute phase response on the plasma clearance of antipyrine, theophylline, phenytoin and nifedipine in.

  14. [Mobilization of Ca2+ from intracellular stores of spermatozoa of Bos taurus depending on their functional status].

    Science.gov (United States)

    Denisenko, V Yu; Boytseva, E N; Kuzmina, T I

    2015-01-01

    On the basis of inhibitory analysis by using a fluorescence probe chlortetracycline, calcium transduction pathway in spermatozoa of Bos taurus has been examined. Additional release of Ca2+ from intracellular stores of sperm was found after combiened action of prolactin and GTP, which took place under influence of protein kinase C inhibitor (compound Ro 31-8220); the combined effect of theophylline and GDP also stimulated additional release of Ca2+ from intracellular stores, which was missing when adding inhibitor of protein kinase A, compound H-89. Using chlortetracycline test (analysis localization of chlortetracycline fluorescence in spermatozoa), we have shown the combined action of prolactin and GTP increases the number of sperm with acrosome reaction, which is reduced after influence of Ro 31-8220; the combined effect of theophylline and GDP increases the percentage of capacitated spermatozoa, which was decreased in the presence of H-89. According with the data obtained, we propose the hypothesis that the transduction of Ca2+ between intracellular stores in bull spermatozoa stimulated by the combined action of prolactin and GTP, or theophylline and GDP, determines the functional status of the spermatozoa. Namely: the transduction of Ca2+ between intracellular stores in bull spermatozoa stimulated by the combined action of prolactin and GTP is involved in the regulation of acrosomal processes, while sperm capacitation is mediated by the transduction of calcium between intracellular stores activated by the combined influence of theophylline and GDP.

  15. APPLICATION OF A POLYSACCHARIDE DERIVED FROM ...

    African Journals Online (AJOL)

    A hydrophilic polysaccharide obtained from Treculia africana fruit was employed as a release matrix for theophylline hydrate tablets. The polysaccharide was employed at concentration levels of 0-30%w/w and tablets were formulated using the wet granulation method. There was a relatively prolonged release of ...

  16. Proceedings of the Combined Effects of Multiple Stressors on Operational Performance Held in San Diego, California on 4-5 April 1989

    Science.gov (United States)

    1989-04-05

    shipboard deployed SEALs. The use of thermogenic drugs (theophylline and caffeine) have been effective in cold air but do not appear to be useful under...essentially without fear, that ’they can go limitless amounts of time without food or without sleep and that they have infinite capacity for sex. It’s

  17. Drug interactions: 1998 update.

    Science.gov (United States)

    1998-12-01

    (1) The 1998 edition of the Drug Interactions section of the French data sheet compendium (Dictionnaire Vidal) includes welcome updates. (2) Increasingly numerous interactions involve tramadol, clarithromycin, oral anticoagulants, antiepileptics, theophylline and various psychotropic agents. (3) An entire section is now devoted to the numerous potassium-raising drugs.

  18. Rate-controlled rectal drug delivery in man with a hydrogel preparation

    NARCIS (Netherlands)

    de Leede, L.G.J.; Boer, A.G.; Pörtzgen, E.; Feijen, Jan; Breimer, D.D.

    1986-01-01

    Cylindrical hydrogels of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent were prepared by radical polymerization at 70°C. After washing they were soaked in an aqueous drug solution of antipyrine or theophylline. The in vitro drug release experiments

  19. Disease: H01841 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ncephalopathy in Japan, and is often observed in children with neurological problems, such as intellectual d...kasaka M, Anzai Y, Mizuguchi M ... TITLE ... Clinical and genetic features of acute encephalopathy in childr...en taking theophylline. ... JOURNAL ... Brain Dev 37:463-70 (2015) DOI:10.1016/j.braindev.2014.07.010

  20. Patients Aged 80 Years or Older are Encountered More Potentially Inappropriate Medication Use

    Directory of Open Access Journals (Sweden)

    Li Mo

    2016-01-01

    Conclusions: The finding from this study revealed that inpatients aged 80 years or older encountered more PIM use than those aged 65-79 years. Anticholinergic properties, megestrol, antipsychotics, theophylline, and aspirin are medications that often prescribed to inpatients aged 80 years or older. Doctors should carefully choose drugs for the elderly, especially the elderly aged 80 years or older.

  1. topics revised

    African Journals Online (AJOL)

    Chantel

    likely to be enhanced by MDAC. This form of treatment should be considered if a patient has ingested a life-threatening quantity of carba- mazepine, dapsone, phenobarbi- tone, quinine or theophylline. MDAC may also increase the elim- ination of amitriptyline, dextro- propoxyphene, digoxin, phenytoin, nadolol and sotalol.

  2. Initiation of smell function in patients with congenital hyposmia.

    Science.gov (United States)

    Henkin, Robert I; Abdelmeguid, Mona; Knöppel, Alexandra B

    2016-01-01

    Patients with congenital smell loss (hyposmia) are born without a sense of smell. They comprise two types. Type I patients have genetic abnormalities manifested by brain, gonadal and other somatic abnormalities. Type II patients have neither a family history of smell loss nor any somatic abnormalities. No systematic attempts to initiate smell function in Type II patients have been reported. Smell function was measured in 19 Type II congenital smell loss patients by both subjective responses and by olfactometry using measurements of detection and recognition thresholds, magnitude estimation and hedonics in response to four odors (pyridine, nitrobenzene, thiophene and amyl acetate) before and after treatment with oral theophylline, 200-800mg daily for periods of 2-36months with evaluation of smell function and serum theophylline measured at intervals of 2-6months. In 12 of the 19 Type II patients (63%) smell function was initiated for the first time and was quantitated by both subjective responses and by olfactometry. Initiation of smell function occurred after treatment with 200-800mg of oral theophylline for periods of 2-19months. This is the first systematic demonstration of initiation of smell in patients who were born without smell function. Oral theophylline presumably acts to increase both olfactory receptor growth, development and perpetuation and brain plasticity which enables them to recognize olfactory signals with initiation of olfactory function. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Author Details

    African Journals Online (AJOL)

    Rahman, M. Vol 11, No 2 (2012) - Articles Interaction of Ketotifen Fumarate with Anhydrous Theophylline in Simulated Gastric and Intestinal Media and Effect on Protein Binding Abstract PDF · Vol 11, No 5 (2012) - Articles Caesarean Risk Factors in Northern Region of Bangladesh: A Statistical Analysis Abstract PDF.

  4. Gradation of microcapsule wall porosity by deposition of polymer mixtures (Eudragit RL and Eudragit RS). Phase separation of polymer mixtures and effects of external media and conditions on release.

    Science.gov (United States)

    Donbrow, M; Hoffman, A; Benita, S

    1995-01-01

    With the aim of increasing flexibility in controlling release from microcapsules, mixtures of wall polymers varying in porosity were investigated by phase separation. Eudragit RL and RS (polymethylmethacrylate linear backbone polymers) mixtures differing in polar substituent content and porosity were used as the wall material and were deposited using a non-solvent addition method. Release rates increased with polar group content of the mixtures, using theophylline, potassium dichromate or sodium chloride as model core materials. Theophylline release rate had the same relationship to polar group content as found earlier for urea permeation of cast mixed-polymer films. Release was generally accelerated in these systems when the external medium contained sodium lauryl sulphate as a wetting agent but not consistently, decreasing unexpectedly for RL-theophylline microcapsules. Localized dissolution of core substance was visible microscopically during release from single microcapsules. The release rate was sensitive to agitation intensity only at low wall to core ratios. Temperature change revealed only a single release mechanism for sodium chloride by Arrhenius equation treatment. Buffer ions penetrated coatings readily, changing theophylline release rates and providing clear evidence of diffusion via a pore-capillary mechanism.

  5. Pellet manufacturing by extrusion-spheronization using process analytical technology

    DEFF Research Database (Denmark)

    Sandler, Niklas; Rantanen, Jukka; Heinämäki, Jyrki

    2005-01-01

    The aim of this study was to investigate the phase transitions occurring in nitrofurantoin and theophylline formulations during pelletization by extrusion-spheronization. An at-line process analytical technology (PAT) approach was used to increase the understanding of the solid-state behavior...

  6. Formulation and evaluation of matrix microspheres for simultaneous ...

    African Journals Online (AJOL)

    Purpose: The objective of this study was to formulate and evaluate a matrix microsphere system for simultaneous delivery of two anti-asthmatic drugs Salbutamol sulphate and Theophylline which are often indicated for the management of asthma, their frequent dosing may reduce compliance, thus making a prolonged ...

  7. A high throughput platform for understanding the influence of excipients on physical and chemical stability

    DEFF Research Database (Denmark)

    Raijada, Dhara; Cornett, Claus; Rantanen, Jukka

    2013-01-01

    The present study puts forward a miniaturized high-throughput platform to understand influence of excipient selection and processing on the stability of a given drug compound. Four model drugs (sodium naproxen, theophylline, amlodipine besylate and nitrofurantoin) and ten different excipients were...

  8. Effects of β₂-agonists on force during and following anoxia in rat extensor digitorum longus muscle

    DEFF Research Database (Denmark)

    Fredsted, A; Gissel, H; Ortenblad, N

    2012-01-01

    of salbutamol on force recovery were prevented by blocking the Na(+),K(+)- pumps with ouabain or by blocking glycolysis with 2-deoxyglucose. Dibutyryl cAMP (1 mM) or theophylline (1 mM) also improved force recovery remarkably. In anoxic muscles, salbutamol decreased intracellular Na(+), increased (86)Rb uptake...

  9. Buffer-Free High Performance Liquid Chromatography Method for ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a simple, economical and reproducible high performance liquid chromatographic (HPLC) method for the determination of theophylline in pharmaceutical dosage forms. Method: Caffeine was used as the internal standard and reversed phase C-18 column was used to elute the drug and ...

  10. Soy matrix drug delivery systems obtained by melt-processing techniques

    NARCIS (Netherlands)

    Vaz, C.M.; Doeveren, van P.F.N.M.; Reis, R.L.; Cunha, A.M.

    2003-01-01

    The aim of this study was to develop new soy protein drug delivery matrix systems by melt-processing techniques, namely, extrusion and injection moulding. The soy matrix systems with an encapsulated drug (theophylline, TH) were previously compounded by extrusion performed at two different pH values,

  11. Drug release from non-aqueous suspensions. II. The release of methylxanthines from paraffin suspensions

    NARCIS (Netherlands)

    Blaey, C.J. de; Fokkens, J.G.

    1984-01-01

    The release of 3 methylxanthines, i.e. caffeine, theobromine and theophylline, from suspensions in liquid paraffin to an aqueous phase was determined in an in vitro apparatus. The release rates were determined as a function of the pH of the aqueous phase. It was proved that the release process was

  12. Optimization and Development of Swellable Controlled Porosity ...

    African Journals Online (AJOL)

    Purpose: To develop swellable controlled porosity osmotic pump tablet of theophylline and to define the formulation and process variables responsible for drug release by applying statistical optimization technique. Methods: Formulations were prepared based on Taguchi Orthogonal Array design and Fraction Factorial ...

  13. Evaluation of Native and Cross-Linked Acacia Senegal Gums as ...

    African Journals Online (AJOL)

    Fourier transform infrared spectroscopy (FTIR) studies indicated the compatibility of the gums with the model drug, theophylline. Dissolution studies showed AS, Cross-linked var. karensis (CAS) and var. senegal (CAH) can sustain the release of the drug beyond 12 h at higher gum concentrations (p < 0.05) indicating the ...

  14. A non-destructive method for quality control of the pellet distribution within a MUPS tablet by terahertz pulsed imaging

    DEFF Research Database (Denmark)

    Novikova, Anna; Markl, Daniel; Axel Zeitler, J

    2018-01-01

    Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of multiple unit pellet system (MUPS) tablets. MUPS tablets containing different amounts of theophylline pellets coated with Eudragit® NE 30 D and with microcrystalline cellulose (MCC) as cushioning agent were analysed. The...

  15. South African Medical Journal - Vol 86, No 7 (1996)

    African Journals Online (AJOL)

    An evaluative study of the short-term effects of oncedaily, sustained-release theophylline on sleep in nocturnal asthmatics · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Denise Richardt, Helen S. Driver, 803-804 ...

  16. Author Details

    African Journals Online (AJOL)

    Onyechi, JO. Vol 7, No 1 (2009) - Articles Use of dika fat in the formulation of sustained release theophylline tablets and capsules. Abstract · Vol 7, No 1 (2009) - Articles Preformulation compatibility screening of dika fat-drug mixtures using differential scanning calorimetry. Abstract · Vol 9, No 2 (2012) - Articles Auxilliary Dry ...

  17. East African Medical Journal - Vol 80, No 4 (2003)

    African Journals Online (AJOL)

    Effects of theophylline administration and intracranial abnormalities on protective head turning response in preterm infants · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. A Wasunna, 204-206. http://dx.doi.org/10.4314/eamj.v80i4.8643 ...

  18. Author Details

    African Journals Online (AJOL)

    Majid, ASA. Vol 13, No 1 (2014) - Articles Buffer-Free High Performance Liquid Chromatography Method for the Determination of Theophylline in Pharmaceutical Dosage Forms Abstract PDF. ISSN: 1596-9827. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More ...

  19. Chromatographic Separation of Xanthine Derivatives on Single and Mixed-Template Imprinted Polymers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dexian; Hong, Seung Pyo; Row, Kyung Ho [Inha University, Incheon (Korea, Republic of)

    2004-03-15

    We developed in the present study molecular imprinted polymers (MIP{sub s}), using single templates (pentoxifylline, caffeine and theophylline) and mixed-templates (pentoxifylline-caffeine, pentoxifylline-theophylline and caffeine-theophylline). The MIP{sub s} were prepared with methacrylic acid (MAA) as the monomer, ethylene glycol dimetharylate (EGDMA) as the crosslinker and 2,2'-azobis(isobutyronitrile) (AIBN) as the initiator. The obtained polymer particles (particle size after grinding was about 25-35 {mu}m) were packed into a HPLC column (3.9 mm i.d. {Chi} 150 mm). The selectivity and chromatographic characteristics of the MIP{sub s} were studied using acetonitrile as the mobile phase at a flow rate of 0.8 mL/min. UV detector wavelength was set at 270 nm. Different single template MIP{sub s} showed different molecular recognitions to the templates and the structurally analogues, according to the rigidity and steric hindrance of the compounds. Recognition was improved on the mixed-template MIP{sub s} as a result of the cooperation or sum effect of the templates, whereas on the pentoxifylline-theophylline imprinted polymer, the highest selectivity and affinity were obtained. Separations of the test compounds on different polymers were also investigated

  20. Effect of pre-analytical handling on haematological variables in minipigs

    DEFF Research Database (Denmark)

    Olsen, A K; Bladbjerg, E-M; Jensen, A L

    2001-01-01

    Pre-analytical handling may be an important determinant of haematological variables, if analysis is delayed. We investigated the effect of anticoagulants, i.e. tripotassium ethylenediamine-tetraacetic acid (EDTA) and citric acid, theophylline, adenosine, dipyridamole (CTAD), storage time (0.5, 1...

  1. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Jensen, P O; Mortensen, B T; Hodgkiss, R J

    2000-01-01

    -labelling with a mixture of 2-nitroimidazole linked to theophylline (NITP) and bromodeoxyuridine (BrdUrd). The leukaemic cells were identified with the RM124 antibody. In rats inoculated with leukaemic cells the fraction of RM124+ cells was significantly increased from day 20 onwards in the spleen and from day 27...

  2. Author Details

    African Journals Online (AJOL)

    Pachuau, L. Vol 7, No 2 (2008) - Articles Formulation and evaluation of matrix microspheres for simultaneous delivery of salbutamol sulphate and theophylline. Abstract PDF. ISSN: 1596-9827. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

  3. Questionnaire-based analysis of the current level of asthma control and management in Niigata Prefecture, Japan: Changes from 1998 to 2000

    Directory of Open Access Journals (Sweden)

    Takashi Hasegawa

    2004-01-01

    Conclusion: These results indicate that antiinflammatory agents, including inhaled corticosteroids and leukotriene receptor antagonists, contributed to improved asthma control, whereas oral theophylline is characteristically used in Niigata Prefecture, Japan. However, not all asthma-related problems, such as satisfaction in daily life, improved and self-evaluation of asthma control by patients may play a key role in improving their satisfaction in daily life.

  4. Tropical Journal of Pharmaceutical Research - Vol 8, No 3 (2009)

    African Journals Online (AJOL)

    Effect of Coating Solvent Ratio on the Drug Release Lag Time of Coated Theophylline Osmotic Tablets · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. MM Kanakal, MHF Sakeena, MN Azmin, D Yusrida. http://dx.doi.org/10.4314/tjpr.v8i3.44539 ...

  5. Tiotropium as a first maintenance drug in COPD: secondary analysis of the UPLIFT trial

    DEFF Research Database (Denmark)

    Troosters, T; Celli, B; Lystig, T

    2010-01-01

    -term Impacts on Function with Tiotropium (UPLIFT) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting beta-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation...

  6. Use of roughness maps in visualisation of surfaces

    DEFF Research Database (Denmark)

    Seitavuopio, Paulus; Rantanen, Jukka; Yliruusi, Jouko

    2005-01-01

    monohydrate, theophylline anhydrate, sodium chloride and potassium chloride. The roughness determinations were made by a laser profilometer. The new matrix method gives detailed roughness maps, which are able to show local variations in surface roughness values and provide an illustrative picture...

  7. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N

    1998-01-01

    . Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...

  8. Non-linear mixed-effects pharmacokinetic/pharmacodynamic modelling in NLME using differential equations

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Madsen, Henrik

    2004-01-01

    equation (ODE) solver package odesolve and the non-Linear mixed effects package NLME thereby enabling the analysis of complicated systems of ODEs by non-linear mixed-effects modelling. The pharmacokinetics of the anti-asthmatic drug theophylline is used to illustrate the applicability of the nlme...

  9. Tropical Journal of Pharmaceutical Research - Vol 7, No 2 (2008)

    African Journals Online (AJOL)

    Estimation of the release profiles of multi-unit dose tablets of theophylline from the release profiles of their components · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. MU Uhumwangho, RS Okor, 981-986. http://dx.doi.org/10.4314/tjpr.v7i2.14682 ...

  10. ORIGINAL ARTICLES

    African Journals Online (AJOL)

    absorption and local side-effects.>_. .... There is an ... Long-acting inhaled or oral ~2-agonists, theophylline, ipratropium bromide and .... The dilierence in effect for the clinical variables was non- conclusive, as demonstrated in Fig. 1. No serious adverse events were reported during the study. Six patients, 3 in each group ...

  11. if, when and how to treat gastro-oesophageal reflux

    African Journals Online (AJOL)

    neonates) are predisposed to reflux; there might be adverse consequences of not intervening surgically in the ... stimulant such as theophylline will be considered. Persistent symptoms, particularly if temporally ... beneficial effects on gastric emptying and respiratory function.s. However, such infants should be changed to the ...

  12. Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer.

    Science.gov (United States)

    Domvri, Kalliopi; Zarogoulidis, Konstantinos; Zogas, Nikolaos; Zarogoulidis, Paul; Petanidis, Savvas; Porpodis, Konstantinos; Kioseoglou, Efrosini; Hohenforst-Schmidt, Wolfgang

    2017-01-01

    Purpose: Lung cancer remains the leading cause of cancer-related deaths worldwide and novel therapeutic approaches targeting crucial pathways are urgently needed to improve its treatment. Differentiation-based therapeutics (Methylxanthines) and phosphodiesterase inhibitors (type 4 and 5), have been implicated in cancer treatment. Our objectives were to capture any potential anti-tumor effect of these drug combinations with chemotherapeutic agents in vitro. Methods: Theophylline as Methylxanthines, Roflumilast as phosphodiesterase type 4 (PDE4) inhibitor and Sildenafil as phosphodiesterase type 5 (PDE5) inhibitor are the drugs that we combined with the chemotherapeutic agents (Docetaxel, Cisplatin and Carboplatin) in vitro. Lung cancer cell lines (NCI-H1048-Small cell lung cancer-SCLC, A549- Non-small cell lung cancer-NSCLC) were purchased from ATCC LGC Standards. At indicated time-point, following 24h and 48h incubation, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Statistical analysis was performed by GraphPad Prism. Results: In SCLC, following 48h incubation, platinum combinations of carboplatin with roflumilast and sildenafil (p<0.001) and carboplatin with theophylline and sildenafil showed increased apoptosis when compared to carboplatin alone. Concerning the combinations of cisplatin, when combined with roflumilast, theophylline and sildenafil appeared with increased apoptosis of that alone (p<0.001, 24h and 48h incubation). In NSCLC, the 24h incubation was not enough to induce satisfactory apoptosis, except for the combination of cisplatin with roflumilast and theophylline (p<0.05) when compared to cisplatin alone. However, following 48h incubation, carboplatin plus sildenafil, carboplatin plus sildenafil, theophylline and roflumilast showed more cytotoxicity when compared to carboplatin alone (p<0.001). Docetaxel combinations showed no statistically significant results. Conclusion: The synergistic effect of PDE

  13. Use of phosphodiesterase inhibitors and prevalence of self-reported glaucoma in the United States.

    Directory of Open Access Journals (Sweden)

    Stephanie P Chen

    Full Text Available While decreased ocular blood flow is thought to be a possible contributor to glaucoma pathogenesis, it is unclear what role systemic phosphodiesterase inhibitors (PDEi play. We performed a cross-sectional study of a nationally representative sample of the U.S. population to investigate the relationship between the most commonly used PDEi, sildenafil and theophylline, and self-reported glaucoma.We used the National Health and Nutrition Examination Survey 2005-2008 cycles for this observational study. 7,042 participants, aged 40 years and over, responded to a survey item on glaucoma status and were included in the analysis. Multivariable logistic regression models were constructed to evaluate the association between at least 1 year of self-reported PDEi use and prevalent glaucoma. Regressions were adjusted for potential confounding variables, including demographics, socioeconomic status, and general health conditions, and accounted for the complex design of the survey. Sample weights were constructed and used to ensure the generalizability of results.482 respondents self-reported a diagnosis of glaucoma, of which 11 used sildenafil and 20 used theophylline for at least 1 year. Covariates significantly associated with higher odds of glaucoma prevalence in univariable analyses included older age, black race, former smoking status, diabetes, hyperlipidemia, myocardial infarction, and stroke. Conversely, higher education and income were significantly associated with lower odds of glaucoma prevalence. In regression analyses adjusted for demographic and socioeconomic variables, sildenafil (OR = 4.90, CI: 1.24-19.27, p = 0.025 and theophylline (OR = 3.15, CI: 1.46-6.80, p = 0.005 were significantly associated with higher odds of self-reported glaucoma. These associations held after further adjustment with general health behaviors and conditions for both sildenafil and theophylline.Use of sildenafil and theophylline for one or more years was associated

  14. Analisi costo/efficacia della doxofillina vs. teofillina nella terapia dell’asma cronica reversibile dell’adulto

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2002-06-01

    Full Text Available Doxofylline is a methyl-xanthine with bronchodilator activity which clinical efficacy in the treatment of asthma and COPD is equivalent to theophylline. Clinical trials prooved that while doxofylline is as effective as theophylline in the treatment of asthma, it is associated with lesser side effects. For our pharmacoeconomical evaluation, we employed the data of an international multi-centric study that compared the efficacy and tolerability of 12 weeks of treatment with either theophylline 250 mg tid, or doxofylline 400 mg tid, or placebo. The efficacy was evaluated with pulmonary function tests and by recording the number of asthma attacks and beta-2 agonist puffs: doxofylline 1200 mg/day and theophylline 750 mg/day resulted equally effective, but the former resulted better tolerated, as the adverse effects were lesser in number and severity. We performed a cost/effectiveness analysis in order to compare the two treatments, considering the perspective of the Italian health system (SSN and of the Italian society. For the purposes of this analysis, the efficacy indices we considered were two: one simple, consisting in the number of avoided asthma attacks (AAA, and a more complex one, i.e. UATD (Utility Adjusted Therapy Days. For the construction of this index, we extracted the survival curve of the patients remaining in therapy; this curve showed that the cumulative number of therapy days is significantly greater in the doxofylline group, although the percentage of dropouts is similar at the end of the three months: this is due to the fact that the drop-outs in the theophylline group occur earlier after treatment start. The number of therapy days was then weighed for an utility index inversely proportional to the main daily number of avoided asthma attacks, thus obtaining the UATDs. The results of the cost/effectiveness analyses showed that doxofylline dominates theophylline treatment in asthma, as it is less expensive and more effective (in

  15. Relaxant effects of Rosa damascena on guinea pig tracheal chains and its possible mechanism(s).

    Science.gov (United States)

    Boskabady, M H; Kiani, S; Rakhshandah, H

    2006-07-19

    Several therapeutic effects including hypnotic, antispasmodic, treatment of abdominal and chest pain and strengthening the heart have been described for the flowers of Rosa damascena. Therefore in the present study, the relaxant effects of ethanolic extract and essential oils of Rosa damascena on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of ethanolic extract (0.25, 0.5, 0.75, and 1.0g%) and essential oils (0.25, 0.5, 0.75, and 1.0vol.%) in comparison with saline as negative control and four cumulative concentrations of theophylline (0.25, 0.5, 0.75, and 1.0mM) were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60mM KCl (group 1, n=5) and 10microM methacholine in two different conditions including: non-incubated tissues (group 2, n=8) and incubated tissues with 1microM propranolol and 1microM chlorpheniramine (group 3, n=5). In group 1 experiments two final concentrations of essential oil and theophylline and only final concentration of ethanolic extract showed relaxant effects compared to that of saline (p<0.01-0.001). In group 2 three higher concentrations of ethanolic extract and theophylline and all concentrations of essential oil showed concentration dependent relaxant effects compared to that of saline (p<0.05-0.001). In addition, the effect of 0.25 and 0.5g% of essential oils in group 2 was significantly higher than those of theophylline and ethanolic extract (p<0.01 for all cases). However, in group 3 experiments the extract and essential oil of Rosa damascena did not show any significant relaxant effect. There were significant correlations between the relaxant effects and concentrations for ethanolic extract and essential oil and theophylline in groups 1 and 2. These results showed a potent relaxant effect of Rosa damascena on tracheal chains of guinea pigs that was comparable to that of theophylline at concentrations used.

  16. EFFECT OF BRONCHODILATORS ON HEART RATE VARIABILITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    H. H. Shugushev

    2015-12-01

    Full Text Available Aim. To study effect of long-acting theophylline (Theotard, KRKA and combination of salmeterol and fluticasone (Seretide, GlaxoSmithKline on heart rhythm variability (HRV and number of arrhythmic episodes in patients with chronic obstructive pulmonary disease (COPD.Material and methods. 144 patients with COPD and 35 patients of control group were examined. The analysis of HRV and Holter monitoring were made f on 2th and 14th days.Results. Treatment with both drugs led to increase in power of low- and high frequencies and their ratio (LF/HF, decrease in rate of supraventricular and ventricular arrhythmias. Theophylline therapy raised in a number of single and pair supraventricular extrasystoles. Treatment with combination of salmeterol and fluticasone did not change a number of extrasystoles.Conclusion. Combination of salmeterol and fluticasone is more preferable as a broncholytic therapy for patients with COPD and heart rhythm disorders.

  17. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Nesterov, Sergey V; Kemppainen, Jukka

    2007-01-01

    Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF......) muscles during exercise, measured using positron emission tomography. In six healthy young women, BF was measured at rest and then during three incremental low and moderate intermittent isometric one-legged knee-extension exercise intensities without and with theophylline-induced nonselective adenosine...... and with theophylline (P Adenosine receptor blockade did not have any effect on mean bulk BF or BF heterogeneity among the QF muscles, yet blockade increased within-muscle BF heterogeneity in all four QF muscles (P = 0.03). Taken together, these results show that BF becomes less heterogeneous with increasing...

  18. The detection of small organic molecules based on novel functionalized surface plasmon resonance sensors

    Science.gov (United States)

    Zheng, Rui; Cameron, Brent D.

    2010-02-01

    The objective of this study was to develop rapid, inexpensive, and easily applied in vivo phenotyping strategies for characterizing drug-metabolizing phenotypes with reference to the cytochrome P450 (CYP) enzymes in biological fluids. Therefore, the accurate detection of low concentration of theophylline, which can be used as a probe for cytochrome P450 (CYP450) enzymes (e.g. CYP1A2) activity, could benefit drug-metabolizing studies. In this study, a portable, specific, and sensitive functionalized surface plasmon resonance (SPR) sensor using polyacrylamide molecularly imprinted polymers (MIPs) as the highly specific selector is developed for the detection of low concentration theophylline in the presence of other confounding components, such as, caffeine which has a very similar chemical structure.

  19. Application of Surfactant Micellar Solutions as Extractants and Mobile Phases for TLC-Determination of Purine Bases and Doping Agents in Biological Liquids

    Directory of Open Access Journals (Sweden)

    Daria Victorovna Yedamenko

    2015-04-01

    Full Text Available Separation of caffeine and its metabolites (theophylline and theobromine and doping agents (spironolactone, propranolol, and ephedrine and determination of caffeine in serum sample and propranolol and ephedrine in urine were studied on normal-phase thin layers (“Sorbfil-UV-254”. Aqueous organic solvents and aqueous micellar surfactant solutions were compared as the mobile phases for separation. The acceptable separation of purine bases and doping agents was achieved by micellar Thin Layer Chromatography and normal-phase Thin Layer Chromatography. Anionic surfactant solution with added 1-propanol was the best eluent as for caffeine, theophylline, and theobromine separation, as for doping agents. The best characteristics of caffeine extraction from serum, and propranolol and ephedrine from urine were achieved when micellar eluent based on non-ionic Tween-80 surfactant was used. DOI: http://dx.doi.org/10.17807/orbital.v7i1.632

  20. Nanoparticles in plant extracts--factors which influence the formation of nanoparticles in black tea infusions.

    Science.gov (United States)

    Gröning, R; Breitkreutz, J; Baroth, V; Müller, R S

    2001-10-01

    The influence of different factors on the formation of nanoparticles in freshly brewed tea extracts was investigated. A black tea infusion was observed during cooling using photon correlation spectroscopy (PCS). The mean particle size and the number of the nanoparticles increase with decreasing temperature. In the presence of caffeine more particles are formed within the infusion. To study the influence of slight structural differences between methylxanthines, the effect of the addition of caffeine to solutions of freshly prepared decaffeinated tea was compared to that of theophylline and theobromine. In the case of theophylline fewer nanoparticles were formed. Molecular modelling calculations were performed to evaluate the most probable geometries for caffeine-polyphenol complexes. A parallel position and a congruent orientation of the 6-membered ring of caffeine and the aromatic galloyl group is the most probable geometry.

  1. Preparation in high-shear mixer of sustained-release pellets by melt pelletisation.

    Science.gov (United States)

    Voinovich, D; Moneghini, M; Perissutti, B; Filipovic-Grcic, J; Grabnar, I

    2000-08-10

    The preparation of sustained-release pellets by melt pelletisation was investigated in a 10-l high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline as a model drug. A translated Doehlert matrix was applied for the optimisation of process variables and quality control of pellets characteristics. After determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis. Finally, the in vitro release from every single size fraction was evaluated and the release mechanism was analysed. Since the drug release rate decreased when enhancing the pellet size fraction, the 2000-microm fraction, exhibiting a substantially zero-order release, was selected for further in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formulate sustained release pellets for theophylline.

  2. Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy.

    Science.gov (United States)

    Baias, Maria; Widdifield, Cory M; Dumez, Jean-Nicolas; Thompson, Hugh P G; Cooper, Timothy G; Salager, Elodie; Bassil, Sirena; Stein, Robin S; Lesage, Anne; Day, Graeme M; Emsley, Lyndon

    2013-06-07

    A protocol for the ab initio crystal structure determination of powdered solids at natural isotopic abundance by combining solid-state NMR spectroscopy, crystal structure prediction, and DFT chemical shift calculations was evaluated to determine the crystal structures of four small drug molecules: cocaine, flutamide, flufenamic acid, and theophylline. For cocaine, flutamide and flufenamic acid, we find that the assigned (1)H isotropic chemical shifts provide sufficient discrimination to determine the correct structures from a set of predicted structures using the root-mean-square deviation (rmsd) between experimentally determined and calculated chemical shifts. In most cases unassigned shifts could not be used to determine the structures. This method requires no prior knowledge of the crystal structure, and was used to determine the correct crystal structure to within an atomic rmsd of less than 0.12 Å with respect to the known reference structure. For theophylline, the NMR spectra are too simple to allow for unambiguous structure selection.

  3. EP4 and EP2 receptor subtypes involved in colonic secretion in rat

    DEFF Research Database (Denmark)

    Mosa, A.S.; Hansen, M.B.; Tilotta, C.M.

    2008-01-01

    EP receptor selective agonists were employed on stripped rat colon pre-treated with indomethacin and theophylline. Receptor-specific agonists were butaprost (EP2), sulprostone (EP1 and EP3) and PGE(1) alcohol (OH-PGE(1)) (EP4). GW627368X was used as a specific EP4 receptor antagonist. Forskolin......-induced SCC was used as a control of tissue viability. The mean basal SCC was 24.5 +/- 0.9 mu A/cm(2) (range 9.8-45.1), and mean basal slope conductance was 23.7 +/- 6.1 mS/cm(2) (range 9.7-39.8). The basal SCC decreased after pre-treatment with indomethacin and increased after pre-treatment with theophylline...

  4. Override of the radiation-induced mitotic block in human tumour cells by methylxanthines and its relationship to the potentiation of cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Musk, S.R.R.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1990-06-01

    Caffeine, theophylline, theobromine and paraxanthine, were tested for ability to override mitotic block induced by ionizing radiation in the human bladder carcinoma cell line RT112. All were found to partially override the block, at a concentration of 1mM in the order caffeine > theophylline > theobromine = paraxanthine. At a concentration of 1 mM only caffeine was found to potentiate cell killing as well as causing block override; at higher concentrations all had a significant effect on survival but little or no further influence on the degree of block override. It is concluded that override of a mitotic block is not in itself sufficient to cause increased killing when irradiated cells are incubated in the presence of caffeine, and that caffeine exerts its potentiating effect by directly inhibiting repair of damage in DNA or by causing override of radiation-induced inhibition of DNA synthesis. (author).

  5. Polyurethane/Poly(2-(Diethyl AminoEthyl Methacrylate blend for drug delivery applications

    Directory of Open Access Journals (Sweden)

    María Gabriela Echeverría

    2015-08-01

    Full Text Available AbstractA pH-sensitive blend of polyurethane (PU and poly(2-(diethyl aminoethyl methacrylate (PDEA with good film-forming capacity was prepared from the corresponding aqueous dispersions. The polymer matrix was first characterized by using FTIR, DSC, water vapor transmission and water swelling capacity at different pHs. The drug release profile of films was evaluated using a vertical Franz Cell and theophylline as model drug. The water swelling degree increases from 54 to 180% when the pH of the medium is changed from 6 to 2, demonstrating the pH-responsive behavior of the film. The in-vitro release studies indicate that an anomalous transport mechanism governs the theophylline release.

  6. Potential of [{sup 11}C]TMSX for the evaluation of adenosine A{sub 2A} receptors in the skeletal muscle by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi E-mail: ishiwata@pet.tmig.or.jp; Mizuno, Masaki; Kimura, Yuichi; Kawamura, Kazunori; Oda, Keiichi; Sasaki, Toru; Nakamura, Yoshio; Muraoka, Isao; Ishii, Kenji

    2004-10-01

    We examined the potential of [7-methyl-{sup 11}C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([{sup 11}C]TMSX) for the assessment of adenosine A{sub 2A} receptors in muscle. In rodents, specific binding of [{sup 11}C]TMSX was observed in muscle and heart by blockade with A{sub 2A}-selective CSC and non-selective theophylline, but not with A{sub 1}-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [{sup 11}C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.

  7. Screening and quantitative determination of twelve acidic and neutral pharmaceuticals in whole blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Buck, Maike

    2010-01-01

    . The method was fully validated for salicylic acid, paracetamol, phenobarbital, carisoprodol, meprobamate, topiramate, etodolac, chlorzoxazone, furosemide, ibuprofen, warfarin, and salicylamide. The method also tentatively includes thiopental, theophylline, piroxicam, naproxen, diclophenac, and modafinil......We describe a multi-method for simultaneous identification and quantification of 12 acidic and neutral compounds in whole blood. The method involves a simple liquid-liquid extraction, and the identification and quantification are performed using liquid chromatography-tandem mass spectrometry...

  8. Regulation of Cardiovascular Development by Adenosine and Adenosine-Mediated Embryo Protection

    OpenAIRE

    Rivkees, Scott A; Wendler, Christopher C.

    2012-01-01

    Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists include the methlyxanthines caffeine and theophylline. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined how adenosine acts via A1ARs to influence embryo development.

  9. Corticosteroids in acute severe asthma: effectiveness of low doses.

    OpenAIRE

    Bowler, S D; Mitchell, C. A.; Armstrong, J. G.

    1992-01-01

    BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known. METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intra...

  10. US Army Biomedical Laboratory Annual Progress Report, Fiscal Year 1980

    Science.gov (United States)

    1980-10-01

    Irreversible Antiholinesterase: Effects of Theophylline and N6, U2-dibutyryl Adenosine 3’, 5’ -monophosphate on Synthesis and Survival. Toxicol. Appl. Pharmacol...be expected that therapy compounds either enhance respiration or at the very least have no adverse effects on respiration. 43 Heart rate and blood...of anticholinesterase-oxime interactions. In. S. Baker (Ed.) The Correlation of Adverse Effects in Man with Observations in Animals, Procepdinas of

  11. The selection and use of essential medicines: report of the WHO Expert Committee, 2005 (including the 14th Model List of Essential Medicines)

    National Research Council Canada - National Science Library

    2006-01-01

    ... for Human Health Meeting, Canberra, Australia, 15- 17 February 2005 3.9 Update on the Priority Medicines Project 3.10 Collaboration with the International Society of Drug Bulletins 3.11 Discussion 3 3 4 4 5 5 6 6 7 8 8 8 4. Changes made in revising the Model List 4.1 Applications for deletions 4.1.1 Aminophylline and theophylline 4.1.2 Atr...

  12. The Regulation of Blood Flow and Metabolism in Adipose Tissue: Evidence for a Role of Adenosine

    Science.gov (United States)

    1984-10-17

    bone for every mole of triglyceride degraded. The pathway is catalyzed by a series of lipases . The first lipase , hormone-senaitive lipaae... catalyzes the rate-limiting step, the removal of the first fatty acid (Newsholme and Start, 1973). Subsequent hydrolysis is then catalyzed by di- and...9. Percent change in metabolic parameters from the onaet 67 of an intravenous Infusion of saline or theophylline, meaaured at peak drug levels or

  13. Relation of 24-hour urinary caffeine and caffeine metabolite excretions with self-reported consumption of coffee and other caffeinated beverages in the general population.

    Science.gov (United States)

    Petrovic, Dusan; Estoppey Younes, Sandrine; Pruijm, Menno; Ponte, Belén; Ackermann, Daniel; Ehret, Georg; Ansermot, Nicolas; Mohaupt, Markus; Paccaud, Fred; Vogt, Bruno; Pechère-Bertschi, Antoinette; Martin, Pierre-Yves; Burnier, Michel; Eap, Chin B; Bochud, Murielle; Guessous, Idris

    2016-01-01

    Caffeine intake is generally estimated by self-reported consumption, but it remains unclear how well self-report associates with metabolite urinary excretion. We investigated the associations of self-reported consumption of caffeinated drinks with urinary excretion of caffeine and its major metabolites in an adult population. We used data from the population-based Swiss Kidney Project on Genes in Hypertension (SKIPOGH) study. Consumption of caffeinated coffee, decaffeinated coffee and other caffeinated beverages was assessed by self-administered questionnaire. Quantification of caffeine, paraxanthine, theobromine and theophylline was performed by ultra-high performance liquid chromatography tandem mass spectrometry in 24-h urine. Association of reported consumption of caffeinated drinks with urinary caffeine derived metabolites was determined by quantile regression. We then explored the association between urinary metabolite excretion and dichotomized weekly consumption frequency of caffeinated coffee, with Receiver Operator Characteristic (ROC) analysis. In the present analysis, we included 598 individuals (52% women, mean age =46 ± 17 years). Self-reported caffeinated coffee intake was positively associated with 24-h urinary excretions of paraxanthine, theophylline and caffeine (p intakes of decaffeinated coffee and other caffeinated beverages showed no association. In ROC analysis, optimal discrimination between individuals consuming less than one caffeinated coffee/week, vs. at least one coffee, was obtained for 24-h urinary paraxanthine (Area Under Curve (AUC) = 0.868, 95% Confidence Interval (CI) [0.830;0.906]), with slightly lower performance for theophylline and caffeine, whereas theobromine did not allow any discrimination. Our results suggest that reported consumption of caffeinated coffee is positively associated with 24-h urinary excretion of caffeine, paraxanthine, and theophylline, and may be used as a marker of caffeine intake for

  14. Distribution coefficients of purine alkaloids in water-ammonium sulfate-alkyl acetate-dialkyl phthalate systems

    Science.gov (United States)

    Korenman, Ya. I.; Krivosheeva, O. A.; Mokshina, N. Ya.

    2012-12-01

    The distribution of purine alkaloids (caffeine, theobromine, theophylline) was studied in the systems: alkyl acetates-dialkyl phtalate-salting-out agent (ammonium sulfate). The quantitative characteristics of the extraction-distribution coefficients ( D) and the degree of extraction ( R, %) are calculated. The relationships between the distribution coefficients of alkaloids and the length of the hydrocarbon radical in the molecule of alkyl acetate (dialkyl phtalate) are determined. The possibility of predicting the distribution coefficients is demonstrated.

  15. Theobromine Inhibits Uric Acid Crystallization. A Potential Application in the Treatment of Uric Acid Nephrolithiasis

    OpenAIRE

    Felix Grases; Adrian Rodriguez; Antonia Costa-Bauza

    2014-01-01

    Purpose To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. Materials and Methods The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobr...

  16. Supercritical carbon dioxide extraction of methylxanthines from maté tea leaves

    OpenAIRE

    Saldaña, M.D.A.; R. S. Mohamed; Mazzafera, P.

    2000-01-01

    Methylxanthines are alkaloids found in natural products such as tea, coffee and guaraná. These alkaloids are commonly used in cola drinks and pharmaceutical products due principally to their stimulant and diuretic effects on the human organism. In this work, experimental data on the supercritical CO2 extraction of caffeine, theophylline and theobromine from herbal maté tea, a beverage traditionally consumed by the gauchos of southern Brazil, the Argentine, Paraguay and Uruguay, were obtained ...

  17. Computationally-Assisted Approach to the Vibrational Spectra of Molecular Crystals: Study of Hydrogen-Bonding and Pseudo-Polymorphism13

    OpenAIRE

    Nolasco, Mariela M.; Amado, Ana M.; Ribeiro-Claro, Paulo J. A.

    2006-01-01

    A new computationally-assisted methodology (PiMM), which accounts for the effects of intermolecular interactions in the crystal, is applied to the complete assignment of the Raman and infrared vibrational spectra of room temperature forms of crystalline caffeine, theobromine, and theophylline. The vibrational shifts due to crystal packing interactions are evaluated from ab initio calculations for a set of suitable molecular pairs, using the B3LYP/6-31G* approach.The proposed methodology provi...

  18. 3D Simulation of Internal Tablet Strength During Tableting

    OpenAIRE

    Siiriä, Simo Matti; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

    2011-01-01

    This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle–particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and exper...

  19. Programmed evolution for optimization of orthogonal metabolic output in bacteria.

    Directory of Open Access Journals (Sweden)

    Todd T Eckdahl

    Full Text Available Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in

  20. Interactions of xanthines with activated carbon

    Energy Technology Data Exchange (ETDEWEB)

    Navarrete Casas, R. [Inorganic Chemistry Department, Granada University (Ugr), E-18071 Granada (Spain)]. E-mail: rncasas@ugr.es; Garcia Rodriguez, A. [Inorganic Chemistry Department, Granada University (Ugr), E-18071 Granada (Spain); Rey Bueno, F. [Inorganic Chemistry Department, Granada University (Ugr), E-18071 Granada (Spain); Espinola Lara, A. [Inorganic Chemistry Department, Granada University (Ugr), E-18071 Granada (Spain); Valenzuela Calahorro, C. [Inorganic Chemistry Department, Granada University (Ugr), E-18071 Granada (Spain); Navarrete Guijosa, A. [Inorganic Chemistry Department, Granada University (Ugr), E-18071 Granada (Spain)

    2006-06-30

    Because of their pharmaceutical and industrial applications, we have studied the adsorption of xanthine derivates (caffeine and theophylline) by activated carbon. To this end, we examined kinetic, equilibrium and thermodynamic aspects of the process. This paper reports the kinetics results. The experimental results indicate that the process was first order in C and the overall process was assumed to involve a single, reversible adsorption-desorption process obeying a kinetic law postulated by us.