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The pharmacokinetics of fluconazole, a new oral azole, were evaluated in cerebrospinal fluid and sera of eight patients with coccidioidal meningitis. At a dose of 50 mg/day, peak concentrations of 2.5 to 3.5 and 2.0 to 2.3 ,ug/ml occurred at 2 to 6 and 4 to 8 h in serum and cerebrospinal fluid, respectively. At 100 mg/day, peak concentrations of 4.5 to 8.0 and 3.4 to 6.2 ,ug/ml occurred at 2 to 4 and 4 to 12 h, respectively. The mean ratios of the concentration in cerebrospinal fluid to that in serum were 73.8% at 50 mg/day and 88.7% at 100 mg/day. Results suggested that there was a prolonged half-life in both cerebrospinal fluid and serum and that it was slightly longer in the former. Minimal toxicity was noted in 34 patient months of therapy (12 months on 50 mg daily; 22 months on 100 mg daily). After a mean of 4.5 months of therapy, five patients responded to therapy and three were unevaluable. The penetration of fluconazole into cerebrospinal fluid was substantial, toxicity was minimal, and early clinical experience was encouraging. Fluconazole holds promise as the sole or adjunctive therapy for fungal meningitis.Coccidioidal meningitis remains among the most difficult of the fungal infections to treat successfully. Without therapy the mortality is virtually 100%; and despite difficulties with administration, toxicity, and disease relapse, amphotericin B administered into the cerebrospinal fluid (CSF) remains the treatment of choice (10). The search continues for a safe and effective treatment alternative.Fluconazole, a new oral triazole, achieves high concentrations in CSF in experimental animals (12) and has shown efficacy in the treatment of murine coccidioidal meningitis (5). The present study was designed to determine the pharmacokinetics of fluconazole in serum and CSF in humans.

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