Pharmacokinetics of bambuterol during oral administration of plain tablets and solution to healthy adults.
OBJECTIVE
The pharmacokinetics of orally administered bambuterol were investigated in healthy adult subjects, with particular regard to time to steady state, pharmacokinetic linearity, intraindividual variability for the parent drug and its active beta2-adrenergic metabolite terbutaline and bioequivalence between tablet and solution.


METHODS
Twenty-six healthy Caucasian subjects were included and 23 (12 women) completed this open, randomised, crossover study. Racemic bambuterol hydrochloride 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 concentrations and urinary recoveries of bambuterol and terbutaline were measured after single doses and during repeated treatments.


RESULTS
Absorption of bambuterol was biphasic. The initial rate could not be assessed directly, but it was faster than that during the second phase where 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 not dose-linear. Mean terminal half-life of terbutaline was 22 h and steady-state was reached within one week of bambuterol treatment. Contrary to bambuterol, overall pharmacokinetics of terbutaline indicated dose-linearity. Day-to-day intraindividual variation in AUC(0,24 h) of terbutaline, 15% with the tablet, was half that of bambuterol. Urine data indicated that intraindividual variability was slightly smaller with the solution. Tablets were bioequivalent with the solution with regard to terbutaline (90% confidence interval: 87-100%).


CONCLUSIONS
With oral bambuterol steady state was reached within 1 week. Regarding generated terbutaline, pharmacokinetics judged to be were linear, intraindividual variability of AUC at steady state was on average 15% with the tablet, and tablets were bioequivalent with the solution.
Rosenborg
J
J
Experimental Medicine and Clinical Science, Astra Zeneca R & D, Lund and Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Uppsala, Sweden. Johan.Rosenborg@astrazeneca.com
Larsson
P
P
Nyberg
L
L
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000493:pharmacokinetics; D012996:Solutions; D013607:Tablets; D013726:Terbutaline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D001993:Bronchodilator Agents; D011355:Prodrugs; D012996:Solutions; D013607:Tablets; D013726:Terbutaline; C047766:bambuterol