Donnelly R, Elliott H L, Meredith P A, Kelman A W, Reid J L
University Department of Materia Medica, Stobhill General Hospital, Glasgow, United Kingdom.
Hypertension. 1988 Oct;12(4):443-9. doi: 10.1161/01.hyp.12.4.443.
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 in 14 subjects with essential hypertension using an integrated kinetic-dynamic model to calculate individual subject responsiveness in terms of fall in blood pressure per unit change in drug concentration. Nifedipine concentrations were well correlated with the fall in systolic blood pressure in 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 kinetic as well as dynamic information to characterize the antihypertensive response to nifedipine and identify nifedipine concentration-effect relationships in individual hypertensive subjects.
