Pharmacokinetics of prazosin administered as gastro-intestinal-therapeutic-systems to 24 healthy volunteers.
Pharmacokinetics of prazosin was investigated after single dose administrations of four different formulations, according to a randomized trial, to 24 young healthy volunteers: immediate release tablets (3 x 1 mg) used as reference (Treatment A), two new Gastro-Intestinal-Therapeutic-Systems (GITS) containing 2.5 mg (Treatment B) and 5 mg (Treatment C) of prazosin, and a traditional sustained release formulation (4 mg, 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 absorption was sustained and plasma concentrations were maintained at a virtually constant level for a time period close to 24 h. As a result, mean residence time (MRT) of prazosin was considerably increased after GITS 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 extrapolation to multiple dosing situations is difficult, this study demonstrates the potential suitability of prazosin GITS for once daily administrations.
Fourtillan
J B
JB
CEMAF, Poitiers.
Brisson
A M
AM
Couet
W
W
D000328:Adult; D003692:Delayed-Action Preparations; D004064:Digestive System / Q000187:drug effects*; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D011224:Prazosin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D011224:Prazosin