Pharmacokinetics and bioavailability of oral ifosfamide

The bioavailability of oral N,3-bis(2-chloroethyl) tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (ifosfamide) (500-mg gelatine capsules) was investigated in 18 patients with bronchogenic carcinoma. Oral and intravenous (Holoxan) ifosfamide was applicated in a randomized sequence on days 1 and 3 at a dose of 1 g/m2 (n = 12) and 2 g/m2 (n = 6). Ifosfamide determination was performed with N/P flame ionization gas chromatography following derivatization with heptafluorobutyric acid. Orally administered ifosfamide showed relatively fast absorption kinetics. Peak levels were reached within 1 h in both dosage groups. With exception of the absorption phase blood level curves of orally and i.v. administered ifosfamide were identical. The average half-life of ifosfamide was 5.5 h (2 g/m2) and 5.8 h (1 g/m2) with a considerable individual variation in both dosage groups. The bioavailability of oral ifosfamide calculated as ration AUCp.o./AUCi.v. was 1.04 after 1 g/m2 ifosfamide and 0.95 in the 6 patients receiving 2 g/m2 ifosfamide. According to our results i.v. administration of ifosfamide especially in fractioned dosage regimes can be replaced by oral application of the same ifosfamide dose.