PHARMACOKINETICS OF IFOSFAMIDE, 2-DECHLOROETHYLIFOSFAMIDE AND 3-DECHLOROETHYLIFOSFAMIDE IN PLASMA AND URINE OF CANCER-PATIENTS TREATED WITHA 10-DAY CONTINUOUS-INFUSION OF IFOSFAMIDE

The cytotoxic drug ifosfamide is subject to an extensive metabolism. T his 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 substantia l induction of the enzymes responsible for its metabolism, resulting i n a two-fold increase of the clearance. The maximal IF concentration i s reached after 24 h, after which the concentration decreases to a ste ady-state. The dechloro-ethylated compounds can be detected in the pla sma about 8 h after the start of the infusion with plasma half-lives l onger than for IF. Urinary excretion studies revealed that at least a quarter of the IF dose is excreted as inactive compounds.