Name: Ketoconazole (Nizoral)
Class: Antifungal (Imidazole)
Mech.: Interferes w/ergosterol synth ® altered fungal membrane permeability.
Absorption: Absorbed well from GI if contents are sufficiently acidic.
Distribution: Poor CSF at recommended doses. Ok CSF w/high doses.
Metab.: Degraded by liver.
Excretion, t½: Excreted mostly into bile. Only 10-15% appears unchanged in urine. Excreted in milk.
Toxicity/S.E.s: Fewer than Amphoter. or flucytosine. Rare fatal hepatic necrosis. Dose-dependent decrease in testosterone. Toxicities for nursing infants. Rare anaphylactic shock. Can’t be used w/astemizole, terfenadine, loratadine due to inhib. of metabolism. Coadmin. w/ketoconazole ® conc. of cyclosporin. Increases anticoag. response of anticoag drugs. Coadmin w/isoniazid or rifampin ® ¯ ketoconazole.
Utility: DOC for Pseudoallescheria boydii. Alternate for C. albicans, H. capsulatum, B. dermatidis, Paracoccidiodes, C. immitis.
Special Features: Very broad spectrum. Being phased out and replaced with itraconazole and fluconazole.