Cause and prevention of mafosfamide-induced venous pain.

An experimental rat model for the study of venous pain induced by 4-hydroxy-cyclophosphamide (4-OH-CP) derivatives was developed and validated. Using various metabolites and chemical variants of 4-OH-CP it was found that pain induction was independent from the compound's alkylating activity but possibly related to the spontaneous generation of minute amounts of acrolein from the 4-OH-CP molecule. Accordingly, the pain could be prevented by the addition of thiol compounds such as mesna or N-acetyl-cysteine.