Influence of pentobarbital on effect and plasma levels of alprenolol and 4-hydroxy-alprenolol.
Six healthy subjects were given placebo and a single oral 0.2-gm dose of alprenolol (Aptin) before and after 0.1 gm pentobarbital at bedtime for 10 days. The plasma concentrations of alprenolol and its metabolite 4-hydroxy-alprenolol and the inhibition of exercise tachycardia were studied for 7 hr after the alprenolol. Alprenolol and 4-hydroxy-alprenolol plasma levels were decreased by about 40% by pentobarbital but plasma half-lives were unchanged. The inhibition of exercise tachycardia during a 7-hr period was reduced from 14.0% to 10.7% by pentobarbital. The reduction was proportional to the decreased drug plasma levels. There was a significant contribution of the metabolite to alprenolol effect. The estimation of relative potency of metabolite against parent compound was 0.9 before pentobarbital and 1.9 after pentobarbital.
D000328:Adult; D000526:Alprenolol / Q000097:blood* / Q000494:pharmacology; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D005082:Physical Exertion; D013997:Time Factors
D000526:Alprenolol; D010424:Pentobarbital