High-dose ketoconazole for treatment of fungal infections of the central nervous system

P. C. Craven, J. R. Graybill, J. H. Jorgensen, W. E. Dismukes, B. E. Levine

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Mortality and complication rates remain unacceptably high with conventional intravenous and intrathecal therapy for patients with coccidioidal meningitis and intracerebral fungal lesions. We studied the ventricular and lumbar cerebrospinal fluid penetration of ketoconazole and the responses to therapy in two patients receiving ketoconazole orally, 800 mg daily, and amphotericin B intraventricularly for meningeal and extrameningeal coccidioidomycosis. Five patients received only 1200 mg of ketoconazole: one had uncomplicated coccidioidal meningitis, three had obstructive hydrocephalus due to coccidioidal meningitis, and one had a histoplasmal brain abscess. Ketoconazole concentrations in ventricular and lumbar fluid ranged from 0.05 to 1.65 μg/mL 4 and 8 hours after the dose. The mean penetration of ketoconazole (± SD) was 1.9% ± 0.8% for ventricular fluid and 5.4% ± 2.6% for lumbar fluid. Ketoconazole concentrations in cerebrospinal fluid varied directly with those in serum and with cerebrospinal fluid protein content. The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole, into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalUnknown Journal
Issue number2
StatePublished - 1983

ASJC Scopus subject areas

  • Internal Medicine


Dive into the research topics of 'High-dose ketoconazole for treatment of fungal infections of the central nervous system'. Together they form a unique fingerprint.

Cite this