Pharmacokinetic characteristics of bornaprolol in healthy volunteers

1. Six young male volunteers received five single doses of bornaprolol, i.v. (20 mg) and orally (120, 240, 480, 960 mg) administered at 2-week intervals. Plasma concentrations of bornaprolol and its conjugated metabolite were determined by gas chromatography. 2. After i.v. administration, plasma bornaprolol levels were detectable over 8 h, and mean values were 60 l/h for total clearance (C1), 207 l for volume of distribution (V beta), 2.6 h for elimination half-life (t1/2 beta). After oral administration, plasma bornaprolol levels were detectable over 24-48 h, and mean values of pharmacokinetics parameters were 60 l/h for C1, 1500 l for V beta, 20 h for t1/2 beta. Maximum plasma concentrations and area under the plasma concentration-time curve increased in a non-dose-dependent manner. 3. The glucuronide conjugate appeared in the blood within 5-10 min and its plasma level greatly exceeded bornaprolol concentrations. The mean value of the ratio of the metabolite AUC/parent product AUC was 14 after i.v. administration and 13-21 following oral administration, depending on dose. The AUC for the metabolite did not increase proportionally with oral doses. 4. Bornaprolol is principally eliminated after metabolism. This process did not increase with increasing oral doses and bioavailability seemed to decrease inversely with oral dose.