PHARMACOKINETICS OF PRAZOSIN ADMINISTERED AS GASTRO-INTESTINAL-THERAPEUTIC-SYSTEMS TO 24 HEALTHY-VOLUNTEERS

Pharmacokinetics of prazosin was investigated after single dose admini strations of four different formulations, according to a randomized tr ial, to 24 young healthy volunteers: immediate release tablets (3 x 1 mg) used as reference (Treatment A), two new Gastro-Intestinal-Therape utic-Systems (GITS) containing 2.5 mg (Treatment B) and 5 mg (Treatmen t C) of prazosin, and a traditional sustained release formulation (4 m g, treatment D). Relative bioavailability of prazosin administered as GITS was only 49.4 +/- 19.5% (B) and 45.5 +/- 18.7 (C) versus 73.8 +/- 13.9% (D) (area under the curve normalized at 3 mg dosing); but absor ption was sustained and plasma concentrations were maintained at a vir tually constant level for a time period close to 24 h. As a result, me an residence time (MRT) of prazosin was considerabiy increased after G ITS administration: 21.6 +/- 1.0 h (B), 22.5 +/- 1.6 h (C) instead of 5.9 +/- 0.2 h for the reference formulation (A) and 10.8 +/- 0.8 h for the traditional sustained release formulation (D). Although extrapola tion to multiple dosing situations is difficult, this study demonstrat es the potential suitability of prazosin GITS for once daily administr ations.