PREDICTION OF THE ANTIHYPERTENSIVE RESPONSE TO ENALAPRIL

This study investigates the potential utility of a drug concentration-effect modelling approach to predict the long-term response to antihypertensive treatment with enalapril. Concentration-effect relationships were characterized in 13 subjects following a single dose of enalapril (20 mg) and for each individual the derived parameters were used to predict the steady-state blood pressure profile. The predicted responses (before dosing and 4 h after dosing) were in close agreement with the responses observed after 6 weeks. In individual patients, the observed and predicted blood pressure profiles over a 12 h period were compared. In six of the 13 subjects, there were statistically significant (P < 0.05) prediction errors. However, in all but one of these patients the error was < 10%, and for the group as a whole the mean prediction error was small and not statistically significant (-0.6 +/- 2.1 mmHg). The kinetic-dynamic parameters derived from observations of the first dose were used to simulate steady-state responses to several alternative doses and dose frequencies. A regimen of 10 mg twice daily increased the ratio of blood pressure at trough-to-peak response to 75 +/- 5% compared to 33 +/- 16% when 20 mg was given once daily. In addition, a twice-daily regimen reduced the coefficient of variation of the hourly average blood pressure. Thus, concentration-effect parameters derived from the first dose response to enalapril have potential not only for predicting long-term antihypertensive response, but also for optimizing dosage regimens for individual patients.