The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide bioactivation.

Aims: The role of CYP pharmacogenetics in the bioactivation of cyclophosphamide is still controversial. Recent clinical studies have suggested a role for either CYP2C19 or CYP2B6. The aim of this study was to clarify the role of these pharmacogenes.

Influence of mustard group structure on pathways of in vitro metabolism of anticancer N-(2-hydroxyethyl)-3,5-dinitrobenzamide 2-mustard prodrugs.

The dinitrobenzamide mustards are a class of bioreductive nitro-aromatic anticancer prodrugs, of which a phosphorylated analog (PR-104) is currently in clinical development. They are bioactivated by tumor reductases to form DNA cross-linking cytotoxins. However, their biotransformation in normal tissues has not been examined.

Hepatic nitroreduction, toxicity and toxicokinetics of the anti-tumour prodrug CB 1954 in mouse and rat.

5-(Aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954), a promising anti-tumour compound, is associated with clinical hepatotoxicity. We have previously demonstrated that human liver preparations are capable of endogenous 2- and 4-nitroreduction of CB 1954 to generate highly potent cytotoxins. The present study initially examined the in vitro metabolism of CB 1954 in S9 preparations of several non-clinical species and strains.