Pharmacokinetics and pharmacodynamics of conventional and controlled-release formulations of metipranolol in man.
The pharmacokinetics and beta-adrenoceptor blocking effects of conventional and sustained-release metipranolol have been studied in 6 healthy male volunteers given a single oral dose of 40 mg. Plasma drug concentrations determined by TLC and a radioreceptor assay, and the inhibition of exercise-induced tachycardia, were monitored for 48 h. Relevant amounts of active metabolites other than deacetylmetipranolol were not found. Compared to conventionally formulated metipranolol, the controlled-release product had a prolonged mean residence time (10.7 vs 5.5 h), the peak drug concentration was halved and the time to peak drug concentrations was delayed. Relatively constant plasma concentrations (cideal = 6.5 ng/ml) and a clinically significant reduction of exercise-induced tachycardia were maintained throughout a 24 h dosing interval. An individual deacetylmetipranolol plasma concentration-effect relationship was evaluated using the Emax model. Mean parameters were Emax 26% and C50 2.9 ng/ml.
Lapka
R
R
Research Institute for Pharmacy and Biochemistry, Prague, Czechoslovakia.
Sechser
T
T
Rejholec
V
V
Peterková
M
M
Votavová
M
M
D000319:Adrenergic beta-Antagonists; D000328:Adult; D002855:Chromatography, Thin Layer; D003692:Delayed-Action Preparations; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D014290:Metipranolol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011412:Propanolamines / Q000493:pharmacokinetics*; D011869:Radioligand Assay
D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D011412:Propanolamines; D014290:Metipranolol