MULTIPLE ORAL DOSE PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF A SUSTAINED-RELEASE FORMULATION OF BUNAZOSIN (E1015) IN HEALTHY-VOLUNTEERS

The results of short term (8-day) and longer term (28-day) pharmacokinetic studies in healthy male volunteers (n = 27) indicate that steady-state plasma bunazosin concentrations are achieved within 8 to 14 days on initiating multiple oral dose administration of a sustained-release formulation of bunazosin (Bunazosin Retard(R)) 6 mg once daily. There is no evidence of bunazosin accumulation with multiple oral dose administration. Bunazosin Retard(R) 6 mg/day did not significantly affect sitting or standing blood pressure, but caused a modest tachycardia (particularly during the first week of administration), a significant increase in cardiac index (+35%), and tended to increase renal artery blood flow (+13%); stroke index was unchanged. The 12-lead ECG revealed no clinically significant changes in cardiac rhythm. conduction or ECG morphology.