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Gender‐Specific Effects on Verapamil Pharmacokinetics and Pharmacodynamics in Humans
Author(s) -
KrecicShepard Mary Ellen,
Barnas Crissy R.,
Slimko Jill,
Jones Michael P.,
Schwartz Janice B.
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700022008883
Subject(s) - verapamil , pharmacokinetics , pharmacodynamics , bioavailability , pharmacology , medicine , heart rate , endocrinology , blood pressure , calcium
Pharmacokinetic studies of i.v. and oral racemic verapamil and 14 C‐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 × 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.