Pharmacokinetics of ifosfamide, 2- and 3-dechloroethylifosfamide in plasma and urine of cancer patients treated with a 10-day continuous infusion of ifosfamide.

The cytotoxic drug ifosfamide is subject to an extensive metabolism. This study reports the results of a pharmacokinetic study of the parent drug and the two dechloroethylated metabolites in 22 patients on a 10-day continuous infusion of ifosfamide. Ifosfamide causes a substantial induction of the enzymes responsible for its metabolism, resulting in a two-fold increase of the clearance. The maximal IF concentration is reached after 24 h, after which the concentration decreases to a steady-state. The dechloro-ethylated compounds can be detected in the plasma about 8 h after the start of the infusion with plasma half-lives longer than for IF. Urinary excretion studies revealed that at least a quarter of the IF dose is excreted as inactive compounds.