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1996-02-26
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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).