Pharmacodynamic modeling of the antihypertensive response to amlodipine.
The distinctive pharmacokinetic characteristics of amlodipine, particularly the long half-life, are presumed to translate directly to a prolonged duration of action, but the concentration-effect relationship for the antihypertensive response has not been clearly established. In this study of 12 patients with essential hypertension, treatment with 5 mg amlodipine once daily has been evaluated with use of an integrated pharmacokinetic-pharmacodynamic model to calculate individual patient responsiveness for the decrease in blood pressure per unit change in drug concentration. Amlodipine concentrations were well correlated with the placebo-corrected reductions in blood pressure in individual patients and responsiveness, for example, for erect systolic blood pressure was -3.1 +/- 0.9 mm Hg/ng/ml. By characterizing the concentration-effect relationships in individual patients, this study has confirmed that the plasma concentration-time profile is an appropriate index of the effect-time profile, as reflected by an antihypertensive response that is sustained throughout 24 hours with relatively little trough-to-peak variability.
Donnelly
R
R
Department of Medicine, and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, Scotland.
Meredith
P A
PA
Miller
S H
SH
Howie
C A
CA
Elliott
H L
HL
D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012044:Regression Analysis; D016037:Single-Blind Method
D017311:Amlodipine