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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In patients (n=32) with advanced solid tumours, continuous once daily sunitinib, in escalating doses per cohort, was combined with ifosfamide, 9 g/m2 for 3 days or 6 g/m2 for 5 days, administered every 3 weeks. Neutropenia-related adverse events were dose-limiting toxicities. Sunitinib did not affect ifosfamide PK. Ifosfamide significantly decreased exposure to sunitinib and increased exposure to its metabolite, SU12662. No consistent changes in PD parameters were observed. Ifosfamide produced decreased sunitinib blood levels due to CYP3A induction. As PK interactions cannot explain the relatively low sunitinib doses that can be combined with ifosfamide, synergy in toxicity is likely. Whether this is true for anti-tumour activity needs to be further explored.
Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies. Hamberg P, Steeghs N, Loos WJ et al. Br J Cancer. 2010 Jun 8;102(12):1699-706.

In an animal study in which rats were treated with ifosfamide alone or in conjunction with various P450 inducers and inhibitors, induction of liver P450 2B enzymes by 4-day high-dose phenobarbital (PB) pretreatment significantly decreased the fraction of IF undergoing 4-hydroxylation  from 37% to 22% of total metabolism. Pretreatment with the P450 3A inducer dexamethasone proportionally decreased the AUC for both IF metabolites, without any net impact on the fraction of IF undergoing metabolic activation. These findings demonstrate specific roles for P450 2B and 3A enzymes in catalysing these pathways of IF metabolism in vivo. These studies also highlight several clinically relevant drug interactions that may occur during concomitant administration of IF with drugs and other compounds that modulate hepatic P450 enzyme levels.
Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo. Brain EG, Yu LJ, Gustafsson K et al. Br J Cancer. 1998 Jun;77(11):1768-76.