Antihypertensive Activity, Cardiac Performance and Pharmacokinetics of Bunazosin, a Novel α₁-Adrenoceptor Antagonist, in Patients with Normal and Impaired Renal Function

Summary

In order to investigate the possible impact of chronic renal insufficiency on the pharmacokinetic and pharmacodynamic properties of bunazosin, 3mg of this novel α ₁-adrenoceptor antagonist were administered once daily for 2 weeks to 24 patients with hypertension. 12 of the patients had normal renal function (controls) while 12 others suffered from chronic renal insufficiency.

The mean area under the plasma concentration-time curve in patients with renal insufficiency on day 1 (AUC_0–48) was 142 ± 65.0 ng/ml • h and rose to 242 ± 204.0 ng/ml • h on day 15. In controls, corresponding values were significantly lower (57 ± 42.9 and 95.5 ± 48.9 ng/ml • h, respectively). Plasma clearance of bunazosin was also reduced in renally impaired patients (193 ± 103 ml/min) compared with controls (623 ± 484 ml/min). Stroke volume and cardiac output increased in both groups and returned to baseline values within 24 hours of bunazosin administration. Blood pressure was markedly reduced from baseline values in both groups to a similar extent. The duration of antihypertensive activity lasted at least 12 hours and no loss of activity was observed during the course of treatment. In both groups, a close correlation between plasma concentrations and haemodynamic effects of bunazosin could be demonstrated.