title: Verapamil pharmacodynamics and disposition in young and elderly hypertensive patients. Altered electrocardiographic and hypotensive responses.
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 X kg; p less than 0.05) and very elderly (8.0 +/- 4.1 mL/min X kg; p less than 0.01) when compared with that in young patients (15.5 +/- 4.5 mL/min X kg). Elimination half-life was prolonged in the elderly (7.4 +/- 3.3 h; p less than 0.01) and very elderly (8.0 +/- 1.2 h; p less than 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.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging; D001794:Blood Pressure / Q000187:drug effects*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D014700:Verapamil / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014700:Verapamil