Verapamil Pharmacodynamics and Disposition in Young and Elderly Hypertensive Patients

Abstract

We studied verapamil pharmacodynamics and disposition in seven young, ten elderly, and seven very elderly hypertensive males. Maximal decrease in mean (± SD) blood pressure tended to be greater in the elderly (-13.5 ± 5.9 mm Hg) and the very elderly patients (-15.9 ± 9.6 mm Hg) compared with that in young patients (-7.3 ± 4.2 mm Hg). Disparate effects on heart rate responses were noted with reflex tachycardia in young patients compared with decreases in heart rate among the elderly and very elderly. Sensitivity to verapamil-induced prolongation in electrocardiographic P-R interval was less in the very elderly, and maximal prolongation in P-R interval induced by verapamil was less in the elderly and very elderly. Verapamil disposition was also age related. Total verapamil clearance was decreased in elderly (10.5 ± 3.5 mL/min · kg; p < 0.05) and very elderly (88.0 ± 4.1 mL/ min · kg; p < 0.01) when compared with that in young patients (15.5 ± 4.5 mL/min · kg). Elimination half-life was prolonged in the elderly (7.4 ± 3.3 h; p < 0.01) and very elderly (8.0 ± 1.2 h; p < 0.01) compared with that in young patients (3.8 ± 1.1 h). Our data indicate age- and hypertension-related physiologic changes result in predictable pharmacokinetic changes. However, the complex alterations in verapamil pharmacodynamic responses indicate an interaction between direct drug effects and age- and disease-related changes in hemodynamic and autonomic nervous system function.