Ifosfamide--pharmacologic overview

Ifosfamide and its structural analogue cyclophosphamide are oxazaphosphorine nitrogen mustards, a group of compounds synthesized in West Germany more than 20 years ago. Whereas both chloroethyl groups of cyclophosphamide are attached to the same exocyclic nitrogen, one of ifosfamide's chloroethyl groups is attached to an endocyclic nitrogen. This minor structural change may account for the different pharmacologic behavior of these two compounds as well as their different spectrums of clinical activity and toxicity. Initial clinical trials of ifosfamide explored the use of a single intravenous dose. Hemorrhagic cystitis appeared to be dose-dependent and limited the use of this agent. However, the development of a systemic thiol uroprotector, such as mesna, has overcome this toxicity, permitting higher ifosfamide doses to be administered. Currently, ifosfamide is usually administered daily for five days in combination with mesna. The pharmacology and metabolism of ifosfamide may explain the toxicities associated with this compound and should be considered when designing schedules of administration.