PHARMACOKINETICS OF TROFOSFAMIDE AND ITS DECHLOROETHYLATED METABOLITES

To contribute to effective and safe outpatient treatment, we investiga ted the metabolism of trofosfamide (Trofo) after oral administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years wh o were treated with 150 or 250 mg/m(2) Trofo in combination with etopo side. Serum samples were collected with 13 patients after oral adminis tration, and Trofo and its dechloroethylated metabolites were quantifi ed by gas chromatography. Urine samples were collected from five patie nts and analyzed by same method. Ifosfamide (Ifo) was the main metabol ite in serum and urine (AUC(Trofo):AUC(Ifo) 1:13), whereas cyclophosph amide (Cyclo) was formed in smaller amounts (AUC(Ifo):AUC(Cyclo) 18:1) . Ifo and Cyclo were further oxidized in the chloroethyl side chains t o form 2- and 3-dechloroethylifosfamide in varying quantities. The uri nary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose. Our results confirm former in vitro o bservations about the metabolism of Trofo. The main side-chain metabol ites Ifo and Cyclo can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an intere sting agent for oral chemotherapy.