Using pharmacokinetics in drug therapy. IV: Consideration in applying pharmacokinetic and pharmacodynamic estimates to antihypertensive dosage regimens

Abstract

A theory explaining the pharmacokinetics of drugs with direct and rapidly reversible pharmacologic effects is reviewed, and the application of this theory to individualizing dosage regimens for antihypertensive drugs is discussed. In a few studies, investigators have correlated, under controlled conditions and in a small number of patients, the pharmacokinetic variables needed to individualize minoxidil and clonidine dosage regimens with clinical responses (mean arterial blood pressure). The potential clinical application of these correlations to other antihypertensive drugs was studied by retrospectively analyzing diastolic and mean arterial blood pressure data reported in 26 published studies of seven antihypertensive drugs. The wide interpatient variation recorded in the dose-response plots derived from the published data yielded pharmacodynamic values of little reliability or predictive value in individualizing antihypertensive dosage regimens. Use of retrospective data analysis for obtaining the necessary pharmacokinetic values to individualize antihypertensive dosage regimens is discouraged.