The pharmacokinetics of ifosfamide exhibit considerable interindividual variation. It is a prodrug that is extensively metabolised, chiefly by cytochrome P450 isoenzymes such as CYP3A4 and CYP2B6 in the liver, to both active and inactive metabolites; there is some evidence that metabolism is saturated at very high doses. Although licensed product information states that a mean terminal elimination half-life is about 15 hours after a single high-dose intravenous bolus, most studies at lower doses recorded elimination half-lives of 4 to 8 hours. After repeated doses there is a decrease in the elimination half-life, apparently due to autoinduction of metabolism. It is excreted largely in urine, as unchanged drug and metabolites.
Martindale Complete Drug Reference. Pharmaceutical Press (via Medicines Complete), latest modification: 20-Aug-2010
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Ketoconazole given orally for 4 days, starting 1 day before intravenous ifosfamide (given as a 24-hour infusion), decreased ifosfamide clearance. However, ifosfamide metabolism to active metabolites was decreased, and urinary excretion of ifosfamide was increased. Ketoconazole may decrease the therapeutic efficacy of ifosfamide.
Kerbusch T, et al. Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin. Clin Pharmacol Ther 2001; 70: 132–41.