Discrepancy between in vitro and in vivo antifungal activity of albendazole

T. C. Hardin, L. K. Najvar, J. Rizzo, A. W. Fothergill, M. G. Rinaldi, J. R. Graybill

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Albendazole has in vitro activity against Cryptococcus neoformans and reduced in vitro activity for albendazole when compared with Candida albicans. The major metabolite of albendazole, albendazole sulphoxide showed no in vitro activity against isolates of either fungus. Immunocompetent mice infected intravenously (IV) with C. albicans were treated with albendazole doses of 20-600 mg kg-1 per day in noble agar or sesame oil for per oral (PO) administration, or 80 mg kg-1 per day in DMSO for intraperitoneal (IP) and IV administration for 10 days, and were observed for survival. Mice infected with C. neoformans intracranially received albendazole in daily doses of 600 mg kg-1 prepared in DMSO (IP) or peanut butter/rat chow (PO) for 10 days and were observed for survival. Mortality was not different between the treated and control animals in any study. Plasma samples from uninfected mice dosed with similar formulations and doses of albendazole were analysed by HPLC for albendazole and albendazole sulphoxide. No albendazole could be detected in any sample, while concentrations of albendazole sulphoxide (286-8697 ng ml-1) were observed in all samples. These data suggest that the absence of in vivo activity for albendazole is due to rapid conversion to the inactive albendazole sulphoxide metabolite.

Original languageEnglish (US)
Pages (from-to)153-158
Number of pages6
JournalMedical mycology
Volume35
Issue number3
DOIs
StatePublished - 1997

Keywords

  • Candida albicans
  • Cryptococcus neoformans
  • albendazole
  • antifungal

ASJC Scopus subject areas

  • Infectious Diseases

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    Hardin, T. C., Najvar, L. K., Rizzo, J., Fothergill, A. W., Rinaldi, M. G., & Graybill, J. R. (1997). Discrepancy between in vitro and in vivo antifungal activity of albendazole. Medical mycology, 35(3), 153-158. https://doi.org/10.1080/02681219780001081