Concentration/effect relationship of bunazosin, a selective alpha 1-adrenoceptor antagonist in hypertensive patients after single and multiple oral doses

Abstract

The concentration/effect relationship of bunazosin, a selective alpha-1-adrenoceptor antagonist of the quinazoline class, was established in hypertensive patients after a first dose of bunazosin and after 8 weeks of chronic dosing. The study was part of a placebo controlled, multicenter dose-finding trial with parallel group design. After a wash-out period and a 2-week placebo run-in phase, each 4 patients received either placebo, 3 mg, 6 mg or 12 mg bunazosin o.d. in a slow-release formulation. Concentration/effect analysis based on a sigmoidal Emax-model and the drop in the mean arterial blood pressure application of this model was feasible in 9/11 patients. The EC50 after the first dose was 4.6 +/_ 2.0 ng/ml and increased to 9.1 +/- 7.3 ng/ml at steady-state. The decrease in the average of the responsiveness parameter was mainly due to about three-fold, right-shift in the concentration/effect curves at steady-state in 3 patients, the remaining patients showed no or considerably lesser changes of the EC50. Whereas a significant correlation was observed between the pretreatment mean arterial blood pressure and the height of the maximal effect under bunazosin, no relationship appears between the bunazosin dose, the resulting plasma levels at trough and the corresponding effect.