Voriconazole excretion

The intravenous formulation of voriconazole contains sulfobutyl ether P-cyclodextrin (SBECD). When voriconazole is given intravenously, SBECD is excreted completely by the kidney. Signiflcant accumulation of SBECD occurs with a creatinine clearance below 50 mL/minute. Because toxicity of SBECD at high plasma concenttations is unclear, oral voriconazole is preferred in azotemic patients. 

Rifabutin increases the metabolism of itraconazole, posaconazole and voriconazole, probably, at least in part, by inducing their metabolism by the cytochrome P450 CYP3A subfamily. Fluconazole is largely excreted unchanged in the urine and so it is not affected. The azoles apparently increase rifabutin levels by inhibiting its metabolism, probably by CYP3A4. Raised rifabutin levels can cause uveitis. 

Rifampicin increases the metabolism of the azote antifungals by the liver. However, as fluconazole (unlike ketoconazole, itraconazole and voriconazole) is mainly excreted unchanged in the urine, changes to its metabolism would not be expected to have as marked an etfect as on these other azotes. 

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