Gender-specific effects on verapamil pharmacokinetics and pharmacodynamics in humans.

Abstract:

:Pharmacokinetic studies of i.v. and oral racemic verapamil and 14C-erythromycin breath tests (ERBT) were performed in 84 healthy men (n = 42) and women (n = 42). Verapamil was measured by HPLC, concentration versus time data were analyzed by noncompartmental models, protein binding was measured by equilibrium dialysis, and statistical analyses were performed by ANOVA. Clearance of i.v. and p.o. verapamil was 13.7 +/- 4.3 and 58.4 +/- 35 ml/min/kg (mean +/- SD) in women compared to 12.6 +/- 3.4 and 82.6 +/- 70 ml/min/kg in men (p = 0.076). Bioavailability was higher in women (0.25 +/- 0.09) compared to men (0.20 +/- 0.09, p = 0.019) with a significant Gender x Formulation interaction (p = 0.04). ERBT were higher in women (p < 0.0001). Verapamil (i.v. and p.o.) decreased blood pressure in all subjects with greater heart rate increases after p.o. verapamil in women compared to men (p = 0.041). The findings suggest that sex-specific differences in drug metabolism may occur in both the gut and the liver and involve multiple metabolic pathways and that pharmacokinetic differences will alter pharmacodynamic responses.

journal_name

J Clin Pharmacol

authors

Krecic-Shepard ME,Barnas CR,Slimko J,Jones MP,Schwartz JB

doi

10.1177/00912700022008883

subject

Has Abstract

pub_date

2000-03-01 00:00:00

pages

219-30

issue

3

eissn

0091-2700

issn

1552-4604

journal_volume

40

pub_type

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