Kinetic-dynamic relationships and antihypertensive mechanisms of ketanserin in essential hypertension.

This study of ketanserin illustrates the use of concentration-effect analysis in clinical investigations of antihypertensive mechanisms and the factors responsible for interindividual differences in blood pressure response. Using an integrated kinetic-dynamic model the acute and chronic responses to ketanserin were characterized for each individual patient in terms of blood pressure fall per unit drug concentration. Two principal findings were obtained from this approach. (1) There was a significant reduction in responsiveness to ketanserin during chronic treatment: on average, -0.47 after the first dose compared with -0.25 mmHg/ng per ml after 1 month. (2) There was a significant change in the parameter keq, which characterizes the temporal discrepancy between the time profiles for plasma drug concentration and effect: from a mean value of 0.49 (first dose) to 1.86/h (1 month). There was no significant relationship between the responsiveness to ketanserin and patient age, peripheral alpha 1-adrenoceptor blockade or initial blood pressure. These results suggest that there is a change in the relative contributions of the component antihypertensive mechanisms during continued treatment with ketanserin. Furthermore, there is no clear relationship between patient age and responsiveness to ketanserin.