Concentration-effect analysis of antihypertensive drug responses

Abstract

It is now widely recognized that a rigid stepped-care approach to antihypertensive therapy is not universally appropriate. Individualized treatment may result in good or better blood pressure control and a simpler regimen without troublesome side effects. Successful development of such a strategy depends on accurate characterization of a dose-response relation and quantitative assessment of the response in each individual. In the past such relations have proved to be hard to identify for antihypertensive drugs, often because of inappropriate study design during drug development. Despite failure of earlier studies to identify drug concentration-antihypertensive response relations, use of concentration-effect modeling, which recognizes and characterizes the temporal discrepancy between drug concentration and effect, has proved more successful. By using such approach, it has been possible to characterize the concentration-effect relations after acute and steady-state antihypertensive therapy with prazosin, doxazosin, nifedipine, verapamil, and enalapril. With enalapril and nifedipine, it has been demonstrated that the mathematical parameters of effect derived from the first dose can predict the response to these drugs after 4-6 weeks of treatment. These findings suggest that the definition of individual concentration-effect relations may be of value in the rational choice of antihypertensive drug therapy and optimization of dose and dose frequency. In particular, the approach can provide valuable information on dose-effect relations and should optimize choice of dose intervals in drug development and practice.