Pharmacokinetics and pharmacodynamics of trimazosin in man.

In this study the pharmacokinetics of trimazosin and its major metabolite, CP 23445, were determined, as were also the effects on blood pressure, heart rate, and peripheral vascular alpha-1 receptors. Trimazosin was administered intravenously (100 mg) and orally (200 mg) to six healthy volunteer subjects (24 to 39 years of age). Blood samples were withdrawn from an indwelling intravenous cannula, and supine and erect blood pressure and heart rate recordings were made at frequent intervals over 12 hours. Concentrations of trimazosin and CP 23445 in whole blood were measured by a sensitive and specific high-pressure liquid chromatography-fluorescence assay developed in our laboratory. Both drug and metabolite could be measured after oral and intravenous administration. Pharmacokinetic parameters were obtained by computer-assisted, nonlinear, least-squares-fitting regression analysis. The pharmacokinetic profile of trimazosin was best described by a two-compartment model. The mean (+/- SD) terminal elimination half-life of trimazosin was 2.73 (+/- 0.90) hours. The metabolite concentrations were then incorporated into the model and a simultaneous fit of drug and metabolite carried out. This did not alter the pharmacokinetic profile of the parent drug but did allow the elimination half-life of the metabolite to be calculated as 1.47 +/- 0.65 hours. The bioavailability of oral trimazosin was 61 +/- 28%. Erect blood pressure was reduced for at least 6 hours after both oral and intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)