Aim The purpose of the study was to evaluate the pharmacokinetics of theophylline administered alone and in combination with donepezil HCl following multiple-dose administration of both medicines in healthy volunteers. 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 variations in theophylline pharmacokinetics (studies have shown that donepezil has a significantly greater degree of selectivity for AChE in the central nervous system (CNS) than for butyrylcholinesterase (BuChE) in the periphery [2 3 Clinical tests undertaken in the USA and Europe possess shown that donepezil (5 mg or 10 mg once daily) significantly enhances cognitive and global function in individuals with Alzheimer’s disease [4-7]. Furthermore these studies have shown that donepezil is definitely well tolerated and is not associated with the hepatotoxicity that is commonly seen with acridine-based cholinesterase inhibitors such as tacrine [8]. Phase I studies carried out in the USA [9] have shown that donepezil pharmacokinetics are linear and dose proportional and are characterized by sluggish plasma clearance and a long half-life (70-80 h) [10 11 Although donepezil is definitely metabolized primarily from the JTT-705 P-450 isoenzyme CYP-3A4 and to a lesser degree by CYP-2D6 jeopardized hepatic function does not considerably influence its pharmacokinetic profile [12]. Since its reputation like a broncodilator nearly 50 years back theophylline a methylxanthine alkaloid offers played a significant part in the administration of both severe and chronic reversible airway blockage specifically JTT-705 asthma and chronic bronchitis. Nonetheless it has a slim safety windowpane which along using its variability in disposition makes dosing challenging to forecast and toxicity challenging to avoid. Symptoms of toxicity consist of tachycardia serious JTT-705 restlessness agitation nausea and throwing up especially at high bloodstream concentrations [13 14 The physical position of an individual can significantly alter theophylline rate of metabolism and/or elimination leading to toxic plasma amounts. Several disease areas aswell as advanced age group smoking and weight problems have been proven to impact the pharmacokinetics of theophylline [13]. Earlier reports also have demonstrated how the half-life of theophylline can be long term and plasma clearance reduced in individuals with liver organ disease severe pulmonary oedema and congestive center failing [13 14 Theophylline can be prone to medically significant relationships with other medicines. For example the clearance of theophylline is increased through the concomitant administration of phenytoin [15] substantially. Rifampin and dental contraceptives create smaller sized but appreciable raises in theophylline clearance whereas cimetidine and erythromycin have already been reported to lessen the clearance of theophylline [15]. With this thought the present research was made to determine whether concurrent multiple-dose administration of sustained-release theophylline with donepezil would create medically relevant adjustments in theophylline pharmacokinetics in healthful volunteers. Strategies This research was conducted relative to Great Clinical Practice Recommendations issued from the Western Commission payment (1990). The process was authorized by an unbiased ethics committee and created educated consent was from each volunteer ahead of participation in virtually any research activities. Subjects The analysis human population comprised 12 healthful male topics between 18 and 36 years who have been within 15% of regular weight for his or her elevation and body build predicated on the Metropolitan INSURANCE PROVIDER Height and Pounds Tables (1983). The scholarly study subject matter were all non-smokers and each had normal blood Rabbit polyclonal to ESR1. circulation pressure and ECG at testing. Subjects with proof medically significant cardiovascular respiratory gastrointestinal hepatic endocrine renal neurological psychiatric and/or haematological disease had been excluded through the trial. Topics with a brief history of serious adverse JTT-705 medication reactions or leucopenia serious or multiple allergy symptoms or habitual medication and/or alcohol misuse had been also excluded from getting into the trial as had been those who got participated in additional drug trials in the last 3 months. Process This is an open-label randomized two-period well balanced crossover research. To initiation of Prior.