Ketoconazole therapy of murine cryptococcal meningitis

P. C. Craven, J. R. Graybill, J. H. Jorgensen

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Currently, even optimal therapy of cryptococcal meningitis is associated with appreciable mortality, drug toxicity, and prolonged hospitalization. Ketoconazole, a new oral imidazole, has therefore been evaluated in a murine model of cryptococcosis. Cryptococcal meningitis was induced in BALB/c mice by intracranial injection of Cryptococcus neoformans. The mice developed infection characterized by diffuse meningitis and extracerebral dissemination. Oral ketoconazole therapy prolonged survival of infected mice, but most mice ultimately succumbed to infection. Ketoconazole dramatically reduced the cryptococcal counts in the liver, but had minimal effect on counts in the brain. Paralleling these results were high concentrations of ketoconazole found in lung, spleen, and heart muscle and lower concentrations (2 to 5 μg/ml) found in the brain. The detection of biologically active drug in the brain, and the prolongation of survival afforded by ketoconazole, suggest a potential role for this agent in the therapy of cryptococcal meningitis.

Original languageEnglish (US)
Pages (from-to)696-700
Number of pages5
JournalAmerican Review of Respiratory Disease
Volume125
Issue number6
StatePublished - 1982

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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