Aging of women alters S-verapamil pharmacokinetics and pharmacodynamics

Pharmacokinetics and pharmacodynamics of S-verapamil were studied in 25 healthy nonsmoking women ranging in age from 23 to 33 years (young) and from 63 to 79 years (elderly) after 15-minute intravenous infusions of 0.10 to 0.11 mg/kg. S-Verapamil clearance decreased in an age-related manner (15.7 +/- 3.5 ml/min/kg in young women versus 12 +/- 1.5 ml/min/kg in elderly women; p < 0.0004) and elimination half-life values increased in an age-related manner from 347 +/- 97 minutes in young women to 453 +/- 153 minutes in elderly women (p < 0.05). Neither volume of distribution beta, steady-state volume of distribution, nor protein binding were altered by age. S-Verapamil decreased blood pressure (p < 0.0001), increased PR intervals during sinus rhythm (p < 0.0001), and transiently increased heart rate (p < 0.0001) in both young and elderly subjects. Age-related differences in responses were seen for mean (p < 0.03) and systolic blood pressure (p < 0.002) (greater decreases in the elderly), heart rate (less increase in the elderly; p < 0.0001), and PR intervals during sinus rhythm (less prolongation in the elderly; p < 0.0001). In summary, aging alters S-verapamil pharmacokinetics and pharmacodynamics in women.