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Pharmacokinetics of bambuterol in healthy subjects.

Abstract：

AIMS:To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS:Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bambuterol as a single dose followed by repeated doses once daily for 7 days. Plasma concentrations and urinary excretion of bambuterol and terbutaline were measured. RESULTS:After intravenous administration, renal clearances of bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline 0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both substances. A similar renal clearance of bambuterol was found during oral administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral administration, implying that uptake was rate-limiting. Mean residence time of terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when terbutaline as such was infused. Generated terbutaline had a bioavailability of 36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of the prodrug. Bambuterol was well tolerated. The mean activity of plasma cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between 30-60% during repeated oral dosing. It virtually regained original activity within 48 h after the last dose. CONCLUSIONS:The plasma concentration ofterbutaline fluctuated little during repeated oral administration (mean peak: trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make it suitable for oral once-daily dosage.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Nyberg L,Rosenborg J,Weibull E,Jönsson S,Kennedy BM,Nilsson M

doi

10.1046/j.1365-2125.1998.00695.x

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

471-8

issue

eissn

0306-5251

issn

1365-2125

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

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Pharmacokinetics of bambuterol in healthy subjects.