       Document 0027
 DOCN  M9620027
 TI    A simple and rapid method for preliminary evaluation of in vivo efficacy
       of anti-HIV compounds in mice.
 DT    9602
 AU    Sato A; Kodama M; Abe K; Miki S; Nishimura M; Suyama A; Ogata M; Toyoda
       T; Sugimoto H; Yoshie O; et al; Shionogi Institute for Medical Science,
       Osaka, Japan.
 SO    Antiviral Res. 1995 May;27(1-2):151-63. Unique Identifier : AIDSLINE
       MED/96075702
 AB    In vivo efficacy of anti-HIV compounds is affected by various factors
       such as bioavailability, metabolism, clearance, and toxicity. Here we
       report a simple and rapid method that might be useful for preliminary
       evaluation of in vivo efficacy of anti-HIV compounds. MT-4 cells
       carrying proviral HTLV-1 were infected with HIV-1 in vitro and injected
       into the peritoneal cavity of SCID mice or BALB/c mice. Inoculated cells
       survive for 1-2 days, and support one to two cycles of viral replication
       which can be monitored by RT activity or p24 content in the supernatants
       of peritoneal wash fluids. Test compounds were administered either
       orally or subcutaneously. AZT, DDC and DDI, the nucleoside-type RT
       inhibitors currently in clinical use, all showed potent anti-HIV-1
       activities in this mouse/MT-4 assay. HEPT (E-EBUdM), a non-nucleoside RT
       inhibitor, also showed potent anti-HIV-1 activity in vivo, whereas TIBO
       (R82913), another non-nucleoside RT inhibitor, was less active. In
       protease inhibitors KNI-272 and Ro 31-8959 showed good in vivo
       activities, while KNI-144, a compound closely related to KNI-272, showed
       poor in vivo activity. This mouse/MT-4 assay, although having a number
       of shortcomings as an animal model for HIV-1 infection, may be of some
       practical utility for preliminary evaluation of in vivo efficacy of
       potential anti-HIV compounds.
 DE    Animal  Antiviral Agents/*PHARMACOLOGY  Cell Line  Cell Transplantation
       Drug Administration Schedule  Drug Screening/*METHODS  Human  HIV
       Protease Inhibitors/PHARMACOLOGY  HIV-1/*DRUG EFFECTS/PHYSIOLOGY  Mice
       Peritoneal Cavity  Reverse Transcriptase Inhibitors/PHARMACOLOGY  Virus
       Replication/DRUG EFFECTS  Zidovudine/BLOOD/PHARMACOLOGY  JOURNAL ARTICLE

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

