Itraconazole excretion

Metabollsm/Excretion— Itraconazole is metabolized by the cytochrome P450 3A4 to several metabolites including the major metabolite hydroxyitraconazole. Fecal excretion of the parent drug varies between 3% and 18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. Itraconazole is not removed by hemodialysis. 

Although itraconazole and fluconazole are both triazoles, they are chemically and pharmacologically distinct. Itraconazole (Sporanox) is lipophilic and water insoluble and requires a low gastric pH for absorption. Oral bioavailability is variable, only 50 to 60% when taken with food and 20% or less when the drug is taken on an empty stomach. Itraconazole is highly protein bound (99%) and is metabolized in the liver and excreted into the bile. With initial dosing, the plasma half-life is 15 to 20 hours steady-state serum concentrations are reached only after 2 weeks of therapy, when the half-life is extended to 30 to 35 hours. In lipophilic tissues, drug concentration is 2 to 20 times that found in... 

Digoxin [NE] Increased gastrointestinal absorption and decreased renal excretion of digoxin with itraconazole and ketoconazole. 

Fluconazole is mainly excreted unchanged in the urine and is thus not under the influence of the induction or inhibition of a metabolic pathway. Itraconazole is predominantly metabolized by CYP3A4 and is the only azole with an active metabolite. Itraconazole is also a substrate of P-gp and an inhibitor of P-gp activity. 

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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