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.