1 Pharmacokinetics and pharmacodynamics of R-and S-verapamil and R-and Snorverapamil 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 Cmax, Cmin, 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 tmax values for 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-(r2 = 0.86) and S-verapamil (r2 = 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.

This study examined the effect of gender and body weight on the pharmacokinetic properties of the Nicotine Transdermal System (NTS) (Nicoderm). This NTS was applied for 24 hours to 13 normal-sized men, 13 women, and 13 obese men, all of whom were smokers who had abstained from cigarettes for the previous 24 hours. Pharmacokinetic parameters were determined during a single application of the system. The mean nicotine maximal plasma concentration (Cmax) and area under the curve (AUC) values for women did not differ significantly from those for normal-sized men. Nicotine Cmax and AUC values, however, were significantly lower in obese compared with normal-sized men; nicotine AUC was strongly correlated to body weight and body mass index. Mean apparent nicotine elimination rate constant values were not significantly different between normal-sized and obese men, but the apparent elimination rate constant value was significantly higher in women. The possible clinical significance of the differences in nicotine AUC values with body weight is discussed.