Chronopharmacological study of bunazosin hydrochloride in healthy subjects

Bunazosin, an alpha-1 adrenoreceptor blocking agent, was given orally to six healthy subjects in the morning or in the evening in order to examine the time-dependent variations in the pharmacological effects of the drug. The study was carried out on four occasions in a placebo controlled cross-over design. No significant change was observed in blood pressure either after the morning or the evening dosage. Finger skin blood flow (FSBF) assessed by laser Doppler flowmetry increased significantly after the morning dosage, but not after the evening trial. The plasma concentration of bunazosin in the morning in general had a tendency to be greater than that in the evening. A significant correlation was observed between the plasma concentrations and the increments in the FSBF. These results indicate that the pharmacological effects of bunazosin are greater following morning dosage. The present study supports the concept that the time-dependent differences in the effect of bunazosin are, at least, caused by the time-dependent changes in plasma drug concentration.