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.

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