Nifedipine: Individual Responses and Concentration-Effect Relationships

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 12; no. 4; pp. 443 - 449
• Main Authors: DONNELLY, RICHARD, ELLIOTT, HENRY L., MEREDITH, PETER A., KELMAN, ANDREW W., REID, JOHN L.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.10.1988; Hagerstown, MD Lippincott
• Subjects: Adult; Age Factors; Aged; Antihypertensive agents; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Dose-Response Relationship, Drug; Female; Heart Rate - drug effects; Humans; Male; Medical sciences; Middle Aged; Nifedipine - pharmacokinetics; Nifedipine - pharmacology; Pharmacology. Drug treatments; Human; Hypertension; Controlled release form; Calcium antagonist; Oral administration; Cardiovascular disease; Metabolism; Activity concentration relation; Mathematical analysis; Interindividual comparison; Dosage form; Antihypertensive agent; Pharmacokinetics
• ISSN: 0194-911X; 1524-4563
• 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 cakuiate 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 klnetk as well as dynamic information to characterize the antihypertensive response to nifedipine and identify nifedipine concentration-effect relationships in individual hypertensive subjects.