A pharmacokinetic evaluation of celiprolol in healthy elderly volunteers

Celiprolol is a new cardioselective beta-adrenergic blocking agent. A pharmacokinetic study in young healthy volunteers showed a nonlinear increase in AUC with increasing dose. As celiprolol will be used in elderly patients, it is necessary to establish the pharmacokinetic profile in this population. This study was established to address this question. The study was of three 7-day periods of medication with 14 days' washout between them. The first two periods were a randomized two-way crossover of celiprolol 200 mg and 400 mg, and in the third period all subjects received celiprolol 600 mg. Blood was taken for celiprolol plasma assays, to establish a 24-h profile on days 1 and 7, with trough levels in between. Subjects had a mean (+SD) age of 65.5 +/- 3.6 years (range 60-71). Model independent kinetics were used, as the data did not fit a conventional model. The AUC values (ng X h/ml) were 3,688, 9,092, and 15,020 for the celiprolol doses 200 mg, 400 mg, and 600 mg respectively on day 1, and 3,317, 9,729, and 16,550 respectively on day 7. This shows a nonlinear increase with increasing dose. A steady state was rapidly achieved, as shown by the trough levels. The Cmax for each celiprolol dose was unchanged from day 1 to day 7. The tmax was equivalent for all doses and unchanged from day 1 to day 7. The t1/2 increased slightly from 5 h on day 1 to 7 h on day 7.