Pharmacokinetics and pharmacodynamics of the alpha 1-adrenergic antagonist bunazosin retard in hypertensives.

The pharmacokinetics and pharmacodynamics of an alpha 1-blocker a sustained release formulation of bunazosin (Detantol R, E1015, 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7- dimethoxyquinazoline hydrochloride, CAS 52712-76-2), were investigated in hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The subjects were hospitalized and placed on a constant sodium diet (NaCl 7 g/day) throughout the study. A 6 mg dose of bunazosin was administered orally once a day for 8 days. Measurement of blood pressure (BP) and sampling of blood and urine specimens were made on the first and last days of treatment. A significant decrease in both systolic and diastolic BP was observed after consecutive dosing of bunazosin compared to baseline values over 24 h in the NRF and for 8 h in the IRF. There were no significant differences in plasma profiles of bunazosin in both groups after single and consecutive dosing. The pharmakokinetic parameters of bunazosin in the NRF and IRF groups did not differ after the single and the consecutive dosing, except for plasma peak levels (Cmax) which were significantly higher in the IRF than those in the NRF. There were, however, neither prolongation of apparent elimination half-life (t1/2), nor increase in Cmax, nor area under the plasma concentration-time curve (AUC0-24) after consecutive dosing in both groups. Cumulative urinary excretion rates of bunazosin were less than 1.1% of dose in both groups, and those did not differ significantly between the NRF and IRF groups in both single and consecutive studies.(ABSTRACT TRUNCATED AT 250 WORDS)