Pharmacology of ifosfamide

Ifosfamide is a bifunctional alkylating agent, used as a racemic mixture by intravenous route in the treatment of various tumors. It is an oxazaphosphorine derivative with a structural formula similar to that of cyclophosphamide. As a prodrug it requires activation in the liver by a cytochrome mixed-function oxidase system. Among various metabolites, ifosforamide mustard probably represents the most important cytotoxic compound able to produce irreparable cross-links between DNA strands. Resistance is due to the ability of neoplastic cells to repair DNA damages. Acrolein may induce hemorrhagic cystitis, whereas chloroacetaldehyde may be responsible both for nephro- and neurotoxicity. A thiol donor (mesna) can prevent urotoxic effects but not nephro- and neurotoxicity. Pharmacokinetics is markedly influenced by route of administration and duration of treatment, age, co-medication, liver and renal function.