DARRELL R. ABERNETHY, M.D., Ph.D.; JANICE B. SCHWARTZ, M.D.; ELIZABETH L. TODD, Ph.D.; ROBERT LUCHI, M.D.; ELEANOR SNOW, P.A.
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.
ABERNETHY DR, SCHWARTZ JB, TODD EL, LUCHI R, SNOW E. Verapamil Pharmacodynamics and Disposition in Young and Elderly Hypertensive Patients: Altered Electrocardiographic and Hypotensive Responses. Ann Intern Med. ;105:329–336. doi: 10.7326/0003-4819-105-3-329
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Published: Ann Intern Med. 1986;105(3):329-336.
Cardiology, Coronary Risk Factors, Hypertension, Nephrology, Rhythm Disorders and Devices.
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