Pharmacokinetics of a sustained-release trimazosin tablet formulation

Abstract

Pharmacokinetics and bioavailability of a trimazosin sustained-release tablet (SRT) formulation (300 mg) were studied in healthy volunteers. In the first study of 12 subjects, the bioequivalence of trimazosin, 100 mg, in a standard tablet (ST) and in a capsule was demonstrated. After that, the bioavailability of one SRT (300 mg) was compared with that of the STs, (100 mg three times a day), in 19 subjects. Maximum plasma concentration (C max) after SRT (8.1 ± 3.0 mg/L) was significantly lower than that observed after ST (13.5 ± 2.3 mg/L), time to peak was strongly delayed by a factor 7, and the time when plasma concentrations were higher than half of C max (t C max 2 ) was longer (10.4 ± 3.2 vs 2.3 ± 0.6 hours, p < 0.001). Bioavailability of the SRT (300 mg) as measured by the area under the curve (AUC ∞) was about 65% of the ST. At the seventh dose, after single daily doses of the SRT in 12 subjects, the mean C max values were not significantly higher than after the first dose (8.6 ± 3.2 mg/L vs 7.7 ± 2.2 mg/L), t C max 2 values were the same (10.4 hours), and the AUC 0–24 hr was comparable to AUC ∞ calculated after the first dose. Steady-state plasma concentration of trimazosin was obtained rapidly. No accumulation of trimazosin or its metabolite occurred.