Gender‐Specific Effects on Verapamil Pharmacokinetics and Pharmacodynamics in Humans
抄録
<jats:p>Pharmacokinetic studies of i.v. and oral racemic verapamil and <jats:sup>14</jats:sup>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.</jats:p>
収録刊行物
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- The Journal of Clinical Pharmacology
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The Journal of Clinical Pharmacology 40 (3), 219-230, 2000-03
Wiley
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詳細情報 詳細情報について
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- CRID
- 1362825896000902528
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- NII論文ID
- 30007804150
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- ISSN
- 15524604
- 00912700
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- データソース種別
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- CiNii Articles