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Efficacy of BMS-180194 against experimental cytomegalovirus infections in immunocompromised mice.

Abstract
A new antiviral nucleoside, BMS-180194 [1R-(1 alpha, 2 beta, 3 alpha)]- 2-amino-9[2,3-bis(hydroxymethyl)cyclobutyl]-1,9dihydro-6H-purin-6- one, is a broad spectrum antiviral agent. The antiviral effectiveness of BMS-180194 against murine cytomegalovirus (MCMV) infection in immunocompromised C57BL/6 mice was investigated and was compared to that of ganciclovir (GCV). LP-BM5 murine retrovirus complex-induced immunocompromised C57BL/6 mice were challenged with MCMV then treated intraperitoneally or per os with various doses of BMS-180194 ranging from 30 to 3 mg/kg/day. When administered intraperitoneally, BMS-180194 was effective against MCMV-mediated mortality in a dose-dependent manner demonstrating a 50% protective dose (PD50) of 3.12 mg/kg/day which was comparable to that of GCV. There was a marked reduction in organ MCMV titers in BMS-180194-treated animals (10-10,000- fold lower than the placebo controls). Similar findings were observed when the compound was administered orally. Interestingly, oral BMS-180194 demonstrated a similar antiviral efficacy as that obtained by the parental route of administration suggesting a high oral bioavailability of the compound. Oral ganciclovir treatment, however, required more than a 4-fold higher amount of GCV to confer the same degree of protection obtained by a parenteral route of administration. Oral BMS-180194 was also effective in reducing the organ MCMV titer in genetically severe combined immunodeficient (SCID) mice. The parenteral or oral antiviral efficacy of BMS-180194 was comparable to that of parenteral ganciclovir against MCMV infection in the present study. Doses of BMS-180194 employed in the present study showed no toxicity to mice. These results suggest that BMS-180194 may be of value as an oral antiviral agent for treatment of opportunistic CMV infections in immunocompromised individuals.
AuthorsH Yang, R L Drain, C A Franco, J M Clark
JournalAntiviral research (Antiviral Res) Vol. 29 Issue 2-3 Pg. 233-41 (Mar 1996) ISSN: 0166-3542 [Print] Netherlands
PMID8739602 (Publication Type: Journal Article)
Chemical References
  • Antiviral Agents
  • Guanine
  • lobucavir
  • Ganciclovir
Topics
  • Administration, Oral
  • Animals
  • Antiviral Agents (pharmacology)
  • Cell Line
  • Dose-Response Relationship, Drug
  • Female
  • Ganciclovir (pharmacology)
  • Guanine (analogs & derivatives, pharmacology)
  • Herpesviridae Infections (drug therapy)
  • Immunocompromised Host
  • Injections, Intraperitoneal
  • Leukemia Virus, Murine
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Muromegalovirus (drug effects)

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