One hundred sixty patients were entered in two multicenter protocols to receive 400 to 2,000 mg of ketoconazole once daily for nonmeningeal or meningeal coccidioidomycosis. For 24 h after administration of all doses, mean concentrations in serum exceeded MICs for Coccidioides immitis (trough concentrations, >1 ,ug/ml). Mean peak concentrations occurred 4 to 6 h after administration, ranging from 7 to 17 ,ug/ml for doses of 400 to 2,000 mg. Incremental increases in peak concentrations in serum were greatest at doses of .1,200 mg. To investigate whether long-term therapy altered concentrations in serum, serial data were studied by several methods. The results suggested a trend to increased levels in serum with prolonged therapy, but were not statistically significant. All 168 cerebrospinal fluid (CSF) samples from meningitis patients contained c2.9,ig/ml, and only 6 contained >1 ,ug/ml.
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