Document 1108
 DOCN  M94A1108
 TI    KNI-272: a potent HIV protease inhibitor exhibiting a favorable oral
       bioavailability in beagle dogs.
 DT    9412
 AU    Fukazawa T; Takeuchi N; Fujisawa N; Hattori N; Mimoto T; Abe S; Yuki K;
       Kiso Y; Tomaszewski J; Hayashi H; et al; Pharmaceuticals and
       Biotechnology Laboratory, Japan Energy; Corporation, Saitama.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):207 (abstract no. PB0841). Unique
       Identifier : AIDSLINE ICA10/94371467
 AB    OBJECTIVE: KNI-272 is an HIV protease inhibitor which exerts a potent
       antiretroviral activity against HIV in vitro. In this study, we
       developed an HPLC assay system for quantifying KNI-272 in plasma,
       determined the pharmacokinetics of the drug at a dose of 15 mg/kg in
       beagle dogs, and defined the disposition characteristics and the oral
       bioavailability. METHODS: The test drug for i.v. study was dissolved in
       40% PEG and HCI (pH 1.7) and that for oral administration in 3% citric
       acid. Oral study was also conducted using the tablet. The plasma
       concentration of KNI-272 was measured by a newly established HPLC method
       (quantification limit: < 5 ng/ml) with a fluorescence detector. RESULTS
       AND CONCLUSION: After single i.v. dosing of KNI-272 at 15 mg/kg, KNI-272
       was eliminated from plasma with a half life of 0.44-0.47 hr. In oral
       studies using both the solution and the tablet formulations, the Cmax
       reached 4.0-4.2 microM and 5.0-7.1 microM in male and female dogs,
       respectively. The oral bioavailabilities were 29.2-30.2% and 23.2-26.8%
       in male and female dogs, respectively. These results suggest that target
       plasma levels (0.1-1 microM) can be achieved without unacceptable acute
       toxicity in beagle dogs, and warrant further research.
 DE    Administration, Oral  Animal  Biological Availability  Chromatography,
       High Pressure Liquid  Dogs  Female  HIV Protease
       Inhibitors/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/  *PHARMACOKINETICS
       Injections, Intravenous  Male  Oligopeptides/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/  *PHARMACOKINETICS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).