Abstract
The pharmacokinetics and pharmacologic effects of sustained release urapidil (BKU) were investigated in 6 healthy subjects after repeated oral administration. Thirty mg of BKU was given once a day on the first and seventh days at 7: 00 a.m., and twice a day on the second to sixth days at 7: 00 a.m. and 7: 00 p.m.
The calculated pharmacokinetic parameters on the first day of BKU administration were as follows: time to peak level (tmax), 4.5±0.3hr (mean±S.E.M.); peak concentration (Cmax), 200.9±24.0ng/ml; biological half-life (t1/2), 3.7±0.3hr. On the seventh day, the pharmacokinetic parameters were: tmax, 4.0±0.3hr; Cmax, 268.1± 49.4ng/ml; t1/2, 3.8±0.7hr.
Urapidil and three metabolites, p-hydroxylated urapidil, O-demethylated urapidi1, and uracil-N-demethylated urapidil, were found in urine after BKU administration. The percent excretion ratio of urapidil and its metabolites in 24-hr urine was not affected by repeated BKU administration.
The maximal blood pressure decrease was observed 4 hours in the sitting position after BKU administration, but no significant decrease was found during the study period. There was no significant change in heart rate in the same position. The increase in heart rate after postural change from sitting to standing tended to be reduced after repeated BKU administration. Neither the hormonal value nor the biochemical value was changed by BKU during the study period.
