Absorption Distribution Metabolism and Excretion

Unlike other imidazoles, ketoconazole (Nizoral) can be absorbed orally, but it requires an acidic gastric environment; patients concurrently treated with H2 blockers or who have achlorhydria have minimal drug absorption. Serum protein binding exceeds 90%. The drug is metabolized in the liver and excreted in the bile. The initial half-life of ketoconazole is 2 hours; 8 to 12 hours after ingestion, the half-life increases to 9 hours.

Reductions in renal and hepatic function do not alter plasma drug concentrations, and ketoconazole is not removed by hemodialysis or peritoneal dialysis. Penetration into cerebrospinal fluid is negligible, so that ketoconazole is ineffective in the treatment of fungal meningitis. Since only small amounts of active drug appear in the urine, ketoconazole is not effective in the treatment of Candida cystitis.

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