Cyclophosphamide (CPA)

Cyclophosphamide is converted by mixed-function oxidase enzymes (cytochrome P450 system) in the liver to active metabolites. The main active metabolite is 4-hydroxycyclophosphamide, which exists in equilibrium with its tautomer, aldophosphamide. Most of the aldophosphamide is oxidised by the enzyme aldehyde dehydrogenase (ALDH) to make carboxyphosphamide. A small proportion of aldophosphamide freely diffuses into cells, it is decomposed into two compounds, phosphoramide mustard and acrolein. Acrolein is toxic to the bladder epithelium and can lead to hemorrhagic cystitis. This can be prevented through the use of aggressive hydration and/or mesna. The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells that have low levels of ALDH.