Pharmacokinetics of bambuterol during oral administration of plain tabletsand solution to healthy adults

Aims The pharmacokinetics of orally administered bambuterol were investigat ed in healthy adult subjects, with particular regard to time to steady stat e, pharmacokinetic linearity, intraindividual variability for the parent dr ug and its active beta(2)-adrenergic metabolite terbutaline and bioequivale nce between tablet and solution. Methods Twenty-six healthy Caucasian subjects were included and 23 (12 wome n) completed this open, randomised, crossover study. Racemic bambuterol hyd rochloride was administered orally as 10 mg, 20 mg, and 10 + 20 mg tablets, and as a solution once daily for 2 weeks at about 19.00 h. Plasma concentr ations and urinary recoveries of bambuterol and terbutaline were measured a fter single doses and during repeated treatments. Results Absorption of bambuterol was biphasic. The initial rate could not b e assessed directly, but it was faster than that during the second phase wh ere absorption was rate-limiting for elimination (mean terminal half-life: 16 h). Steady-state AUC(0,24 h) of bambuterol, reached within 1 week, was n ot dose-linear. Mean terminal half-life of terbutaline was 22 h and steady- state was reached within one week of bambuterol treatment. Contrary to bamb uterol, overall pharmacokinetics of terbutaline indicated dose-linearity. D ay-to-day intraindividual variation in AUC(0,24 h) of terbutaline, 15% with the tablet, was half that of bambuterol. Urine data indicated that intrain dividual variability was slightly smaller with the solution. Tablets were b ioequivalent with the solution with regard to terbutaline (90% confidence i nterval: 87-100%). Conclusions With oral bambuterol steady state was reached within 1 week. Re garding generated terbutaline, pharmacokinetics judged to be were linear, i ntraindividual variability of AUC at steady state was on average 15% with t he tablet, and tablets were bioequivalent with the solution.