A simple and rapid method for preliminary evaluation of in vivo efficacy of anti-HIV compounds in mice
Autor: | Masaru Ogata, Miyuki Nishimura, Hirohiko Sugimoto, Tamio Fujiwara, Shigeru Miki, Akihiko Sato, Akemi Suyama, Makoto Kodama, Osamu Yoshie, Kenji Abe, Tatsuo Toyoda |
---|---|
Rok vydání: | 1995 |
Předmět: |
Ratón
Cell Transplantation medicine.medical_treatment Drug Evaluation Preclinical Pharmacology Biology Virus Replication Antiviral Agents Drug Administration Schedule Cell Line Peritoneal cavity Mice In vivo Virology medicine Animals Humans Peritoneal Cavity Protease virus diseases HIV Protease Inhibitors In vitro Bioavailability medicine.anatomical_structure Cell culture Toxicity HIV-1 Reverse Transcriptase Inhibitors Zidovudine |
Zdroj: | Antiviral research. 27(1-2) |
ISSN: | 0166-3542 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |