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Absorption of new HIV‐1 protease inhibitor, KNI‐272, after intraduodenal and intragastric administrations to rats: Effect of solvent
Author(s) -
Sugahara M.,
Kiriyama A.,
Hamada Y.,
Kiso Y.,
Takada K.
Publication year - 1995
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510160403
Subject(s) - pharmacokinetics , pharmacology , chemistry , bioavailability , chromatography , oral administration , solvent , dosage form , absorption (acoustics) , medicine , biochemistry , materials science , composite material
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 HCO60, a polyoxyethylated, 60μmol, castor 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 (Tween 80), and 4.66±0.68 μg mL −1 (PG:HCO60). The highest BA, 44.6%, was obtained after ID administration of KNI‐272 dissolved in PG:HCO60. On the other hand, after intragastric (IG) administration of KNI‐272 solution in which the drug was dissolved with PG:HCO60, the T max , the C max , and the BA were 1.25±0.60h, 2.33±0.65 μg mL −1 , and 24.2%, respectively. The C max 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 HCO60) 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.