Individual Responses and Concentration-Effect Relationships

Dynamic and kinetic variability account for the large intersubject differences in the antihypertensive response to nifedipine, and a clear concentration-effect relationship has not been established. The effects of placebo, first dose, and chronic (1 and 6 weeks) treatment with nifedipine were studied hi 14 subjects with essential hypertension using an Integrated kinetic-dynamic model to cakuiate individual subject responsiveness in terms of fall hi blood pressure per unit change hi drug concentration. Nifedipine concentrations were well correlated with the fall hi systolic blood pressure hi Individual subjects, and the mean responsiveness was —0.48 mm Hg/ng/ml after the first dose, -0 .45 mm Hg/ng/ ml after 1 week, and 0.49 mm Hg/ng/ml after 6 weeks. The responsiveness to the first dose of nifedipine was significantly correlated with the responsiveness after 1 (r = 0.83) and 6 weeks (r = 0.78) of therapy and with the height of the pretreatment blood pressure (r = 0.6). This study incorporated klnetk as well as dynamic information to characterize the antihypertensive response to nifedipine and identify nifedipine concentration-effect relationships hi individual hypertensive subjects. (Hypertension 12: 443-449, 1988)