RT Journal Article
SR Electronic
T1 Stereoselective verapamil disposition and dynamics in aging during racemic verapamil administration.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 904
OP 911
VO 266
IS 2
A1 D R Abernethy
A1 I W Wainer
A1 J A Longstreth
A1 N S Andrawis
YR 1993
UL http://jpet.aspetjournals.org/content/266/2/904.abstract
AB Stereoselective verapamil disposition and dynamics were evaluated after racemic verapamil administration of single i.v. doses, simulated steady-state intravenous infusions, chronic (1 week) administration of oral immediate-release tablets (120 mg three times daily) and chronic (1 week) administration of oral sustained-release tablets (240 mg once daily) to 15 young (mean +/- S.E.M. age 22 +/- 1 year) and 15 older (69 +/- 1 year) healthy male volunteers. After single i.v. doses S-verapamil clearance (young, 102 +/- 6 vs. older, 77 +/- 6 l/hr; P < .01) and R-verapamil clearance (young, 61 +/- 3 vs. older, 45 +/- 3 l/hr; P < .01) were similarly decreased. Electrocardiographic P-R prolongation using S-verapamil concentrations and an Emax model (young Emax, 69 +/- 8 vs. older, 42 +/- 6 msec; P < .05: young EC50, 15 +/- 1 vs. older, 23 +/- 3 ng/ml; P < .05) was greater in the young. Simulated steady-state i.v. S-verapamil clearance (young, 76 +/- 3 vs. older, 49 +/- 2 l/hr; P < .01) and R-verapamil clearance (young, 47 +/- 2 vs. older, 28 +/- 1 l/hr; P < .01) were similarly less in older subjects and this was unrelated to infusion rate. Qualitatively similar findings were observed during chronic oral (immediate release) treatment and chronic oral (sustained release) treatment. Plasma protein binding of S-verapamil was less in both groups (young, 8.5 +/- 0.4 and older, 8.0 +/- 0.5% unbound) than that of R-verapamil (young, 5.4 +/- 0.2 and older, 5.1 +/- 0.3% unbound) and not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)