Absorption of new HIV-1 protease inhibitor, KNI-272, after intraduodenal and intragastric administrations to rats: Effect of solvent

✍ Scribed by M. Sugahara; A. Kiriyama; Y. Hamada; Y. Kiso; K. Takada

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 443 KB
• Volume: 16
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510160403

✦ Synopsis

KNI-272 is a tripeptide drug that has a strong pharmacological potential for treating human immunodeficiency virus type 1 (HIV-1). We have already reported the pharmacokinetic characteristics of KNI-272 after intravenous and intraduodenal (ID) administrations to rats. In this study, KNI-272 was administered to rats as a solution and the effect of four kinds of solvent on the bioavailability (BA) of KNI-272 was determined using rats. The mixtures included propylene glycol (PG) and water (70% PG), a solution of PG (100% PG), a solution of Tween 80 (Tween 80), and a mixture of PG and HC060, a polyoxyethylated, 60 pmol, castor oil derivative (PG:HC060 = 7:3). After ID administration to rats at a dose of 50-0mgkg-', the mean peak plasma concentrations, C , , , were 2.58 f 0.53 (SE) (70% PG), 3-28 f 0-51 (100% PG), 3-15fO.51 (Tween 80), and 4.66+0.68lgmL-l (PGHC060). The highest BA, 44-6%, was obtained after ID administration of KNI-272 dissolved in PG:HC060. On the other hand, after intragastric (IG) administration of KNI-272 solution in which the drug was dissolved with PG:HC060, the T,,, the C , , , and the BA were 1.25 f 0.60 h, 2.33 fO.65 pgmL-', and 24.2%, respectively. The C , , and BA values were equal to half of the values obtained after ID administration of KNI-272 dissolved in the same solution. In this study, as the PG concentration in the solution increased and the other additives (Tween 80 and HC060) were coadministered, 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 intestine and that enhances the absorption of this drug from the gastrointestinal tract into the enterocytes is needed.