AGE AND GENDER-RELATED CHANGES IN STEREOSELECTIVE PHARMACOKINETICS AND PHARMACODYNAMICS OF VERAPAMIL AND NORVERAPAMIL

1 Pharmacokinetics and pharmacodynamics of R- and S-verapamil and R- and S-norverapamil were studied at steady state following administration of 180 mg verapamil delivered by a controlled-release gastrointestinal therapeutic system (COER-verapamil). 2 Of the 30 young (19 to 43 years) and 30 elderly subjects (65 to 80 years) enrolled, approximately half of each age group were women; all subjects were healthy and none were smokers. 3 Mean R- and S-verapamil and R- and S-norverapamil C-max, C-min, and AUC values for elderly subjects were 1.2 to 2.2 times greater than those for young subjects; these differences were statistically significant at P < 0.05. Median t(max) values for max young and elderly subjects were not significantly different for any enantiomer. The mean half-life values of R- and S-verapamil for elderly subjects were approximately 20 h compared with approximately 13 h for young subjects, respectively. The mean half-life values of R- and S-norverapamil for elderly subjects were approximately 31 h and 20 h, respectively, compared with approximately 19 h and 21 h for young subjects, respectively. 4 In both age groups, the mean plasma verapamil concentrations of each enantiomer were higher for women than for men at all time points. 5 Mean arterial pressure (MAP) had a significant correlation to R- (r(2) = 0.86) and S-verapamil (r(2) = 0.87) concentration values that was not influenced by either gender or age of the patient. Change in PR-interval also had a significant correlation to R- and S-verapamil concentration values. However, the sensitivity of the response to changes in R- and S-verapamil concentration values in elderly subjects was about 1/5 of that in younger subjects.