PHARMACOKINETICS AND PHARMACODYNAMICS OF THE ALPHA(1)-ADRENERGIC ANTAGONIST BUNAZOSIN RETARD IN HYPERTENSIVES

The pharmacokinetics and pharmacodynamics of an alpha(1)-blocker a sus tained release formulation of bunazosin (Detantol(R) R, E1015, no-2(4- butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7- dimethoxyquinazoline hydro chloride, CAS 52712-76-2), were investigated in hypertensive patients with normal renal function (NRF) and those with impaired renal functio n (IRF). The subjects were hospitalized and placed on a constant sodiu m diet (NaCl 7 g/day) throughout the study. A 6 mg dose of bunazosin w as administered orally once a day for 8 days. Measurement of blood pre ssure (BP) and sampling of blood urine specimens were made on the firs t and last days of treatment. A significant decrease in both systolic and diastolic BP was observed after consecutive dosing of bunazosin co mpared 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 pharmacokinet ic parameters of bunazosin in the NRF and IRF groups did not differ af ter the single and the consecutive dosing, except for plasma peak leve ls (C-max) which were significantly higher in the IRF than those in th e NRF. There were, however, neither prolongation of apparent eliminati on half-life (t(1/2)), nor increase in C-max, nor area under the plasm a concentration-time curve (AUC(0-24)) after consecutive dosing in bot h groups. Cumulative urinary excretion rates of bunazosin were less th an 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 . Weak but significant inverse correlations were found between the cre atinine clearance and the AUC for bunazosin, but there was no deterior ation in renal function during the study. These results suggest that t he bunazosin preparation has a prolonged duration of antihypertensive effects during consecutive dosing and that a dose adjustment of bunazo sin may be unnecessary in patients having mild to moderate renal dysfu nction.