ABSORPTION OF NEW HIV-1 PROTEASE INHIBITOR, KNI-272, AFTER INTRADUODENAL AND INTRAGASTRIC ADMINISTRATIONS TO RATS - EFFECT OF SOLVENT

KNI-272 is a tripeptide drug that has a strong pharmacological potenti al for treating human immunodeficiency virus type 1 (HIV-1). We have a lready reported the pharmacokinetic characteristics of KNI-272 after i ntravenous and intraduodenal (ID) administrations to rats. In this stu dy, KNI-272 was administered to rats as a solution and the effect of f our kinds of solvent on the bioavailability (BA) of KNI-272 was determ ined using rats. The mixtures included propylene glycol (PG) and water (70% PO), a solution of PG (100% pc), a solution of Tween 80 (Tween 8 0), and a mixture of PC and HCO60, a polyoxyethylated, 60 mu mol, cast or oil derivative (PG:HCO60 = 7:3). After ID administration to rats at a dose of 50.0 mg kg(-1), the mean peak plasma concentrations, C-max, were 2.58+/-0.53(SE) (70% PG), 3.28+/-0.51 (100% PG), 3.15+/-0.51 (Tw een 80), and 4.66+/-0 68 mu g mL(-1) (PG:HCO60). The highest BA, 44.6% , was obtained after ID administration of KNI-272 dissolved in PG:HCO6 0. On the other hand, after intragastric (IG) administration of KNI-27 2 solution in which the drug was dissolved with PG:HCO60, the T-max th e C-max, and the BA were 1.25+/-0.60h, 2.33+/-0.65 mu g mL(-1), and 24 .2%, respectively. The C-max and BA values were equal to half of the v alues obtained after ID administration of KNI-272 dissolved in the sam e solution. In this study, as the PG concentration in the solution inc reased and the other additives (Tween 80 and HCO60) were coadministere d, the BA of KNI-272 after ID administration increased. These results suggest that, for the development of an oral dosage form of KNI-272, a non-ionic surfactant that dissolves in the duodenum or small intestin e and that enhances the absorption of this drug from the gastrointesti nal tract into the enterocytes is needed.