       Document 0688
 DOCN  M9610688
 TI    Absorption of new HIV-1 protease inhibitor, KNI-272, after intraduodenal
       and intragastric administrations to rats: effect of solvent.
 DT    9601
 AU    Sugahara M; Kiriyama A; Hamada Y; Kiso Y; Takada K; Department of
       Pharmaceutics and Pharmacokinetics, Kyoto; Pharmaceutical University,
       Japan.
 SO    Biopharm Drug Dispos. 1995 May;16(4):269-77. Unique Identifier :
       AIDSLINE MED/96031392
 AB    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, 60 mumol,
       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, Cmax,
       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 micrograms 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
       Tmax, the Cmax, and the BA were 1.25 +/- 0.60 h, 2.33 +/- 0.65
       micrograms mL-1, and 24.2%, respectively. The Cmax 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.
 DE    Administration, Oral  Animal  Biological Availability  HIV Protease
       Inhibitors/*PHARMACOKINETICS  HIV-1  *Intestinal Absorption  Kinetics
       Male  Oligopeptides/*PHARMACOKINETICS  Rats  Rats, Wistar  *Solvents
       Time Factors  JOURNAL ARTICLE

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

