Theophylline

Aims The cytochrome P4501A2 (CYP1A2) catalyses the metabolism of a number of clinically used drugs, and thus there is an interest in determining the activity of CYP1A2 in patients before treatment with CYP1A2 substrates. Caffeine is the most commonly used model drug to assess CYP1A2 function, but due to the complex metabolism of caffeine, there is a need for an alternative drug to use as an index of CYP1A2 activity. In this study the CYP1A2 substrate theophylline was tested as a possible alternative to caffeine as a model drug for CYP1A2. Methods Twelve healthy volunteers ingested 200 mg of caffeine, and the caffeine metabolic ratios (CMR), CMRurine=(AFMU+1MX+1MU)/17DMU and CMRplasma=17DMX/137TMX were determined 6 h after drug intake. After a period of about 2 months the volunteers ingested 257 mg theophylline and blood samples were drawn and urine was collected during the following 48 h. The oral and partial clearances of theophylline were calculated via N‐demethylation and 8‐hydro...

Recent studies have shown that the neurotrophins NGF and BDNF are produced by eosinophils. The influence of neurotrophins in allergic diseases including asthma has been described. The regulation by pharmacological substance remains unclear. The aim of this study was to assess whether approved pharmacological substances in the treatment of asthma such as corticosteroids or theophylline regulate neurotrophins on a cellular level. Eosinophils were purified by negative immunoselection from allergics and non-allergic donors. Eosinophils were incubated with dexamethasone and theophylline and supernatants were collected for measurement of neurotrophic factors. The content of neurotrophins in eosinophil lysates was determined by ELISA. Regulation of stored NGF and BDNF was demonstrated by Western-blotting and flow cytometry while influence on transcription level was demonstrated by RT-PCR. Eosinophils produce and release the neurotrophins NGF and BDNF at different levels in allergics and no...

The controlled release drug delivery preserves the efficient concentration of drug in blood and omits the side effect of it. Also, it provides more comfort and high quality of life for patients. Polymers, one of the common substrate of drug delivery systems, usually were used in nano-particle shape, that are one of the appropriate methods for controlled and efficient drug delivery. Among the methods for preparation of nano-particles, electrospray because of its simple control on the rate of deposition, size, and density of particles, low-cost equipment, fabrication in atmospheric condition and low temperature is a unique way.In this study, the theophylline(TF) was encapsulated in PVA by electrospray for controlled release drug delivery purposes. For determining the optimized particle, the first different molecular weights of PVA (23000, 72000 and 144000 gr/mol) were assessed by SEM pictures. Then different concentrations of PVA (5, 10, 13 and 15% w/v) were evaluated by SEM for the b...

Study Objective. To compare the performance of a new point‐of‐care theophylline assay (AccuMeter) with that of a standard laboratory assay (TDx), and another point‐of‐care method (AccuLevel).Design. Prospective evaluation of consecutive patients receiving theophylline.Setting. University‐based, ambulatory, allergy‐pulmonary clinic.Patients. Forty subjects receiving maintenance theophylline therapy for asthma.Interventions. Theophylline concentrations obtained from AccuMeter, TDx and AccuLevel were compared.Measurements and Main Results. The error, or difference, between TDx and AccuMeter results in 40 subjects on maintenance theophylline described accuracy. Mean error, an estimate of bias, was 1.1 (95% CI 0.72–1.5), 0.67 (0.34–1.0), and 0.98 (0.79–1.2) μg/ml for AccuMeter capillary, serum, and heparinized blood samples. Square root of the mean squared error, an estimate of precision, was 1.6 (1.2–2.0), 1.22 (0.90–1.5), and 1.14 (0.96–1.3) μg/ml for AccuMeter capillary, serum, and he...

Assessment in young children of the bioavailability of slow-release theophylline formulations is hampered by the requirement for frequent blood sampling. Calculations of bioavailability from serial serum and passively absorbed saliva samples were therefore compared in six 9- to 12-year-old asthmatic children receiving multiple doses of Theo-Dur Sprinkle every 12 hours, using Theo-Dur tablets, a previously characterized formulation, as a reference. Results indicated 85 ± 5 percent and 82 ± 8 percent (mean ± SEM) relative bioavailability based on serum and salivary measurements, respectively. Correlation coefficient for serum and passively absorbed saliva bioavailabilities was 0.90. Passively absorbed saliva provides an acceptably accurate, noninvasive method for theophylline bioavailability assessment and may be a useful alternative for bioavailability studies in young children.

The cardiovascular effects of the adenosine A1 receptor agonist N6‐cyclopentyladenosine (CPA) and the adenosine A2A receptor agonist 2‐p‐(2‐carboxyethyl)phenethylamino‐5′‐N‐ethylcarboxamidoadenosine (CGS 21680) were investigated in rats implanted with telemetry transmitters for the measurement of blood pressure and heart rate. Intraperitoneal (i.p.) injections of the adenosine A1 receptor agonist CPA led to dose‐dependent decreases in both blood pressure and heart rate. These effects of 0.3 mg kg−1 CPA were antagonized by i.p. injections of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethyl‐xanthine (CPT), but not by i.p. injections of the adenosine A2A receptor antagonist 3‐(3‐hydroxypropyl)‐8‐(m‐methoxystyryl)‐7‐methyl‐1‐propargylxanthine phosphate disodium salt (MSX‐3). Injections (i.p.) of the peripherally acting nonselective adenosine antagonist 8‐sulfophenyltheophylline (8‐SPT) and the purported nonselective adenosine antagonist caffeine also antagonized the cardi...