1974 Volume 114 Issue 1 Pages 55-60
Cyclophosphamide-cytochrome P-450 difference spectrum in microsomes from the rat liver was of type 1. The shape of the difference spectrum indicates that cyclophosphamide is bound to microsomal hemeprotein (P-450). In the in vivo experiments, blood concentra-tions of cyclophosphamide after intraperitoneal administration to rats pretreated with phenobarbital or chloramphenicol were measured. It was found J that the blood levels of the active metabolites of cyclophosphamide (normustard-like substances) in rats pretreated with phenobarbital were higher than those in normal controls, and that those in rats pretreated with chloramphenicol were lower than those in normal controls. Moreover, the levels of microsomal cyto-chrome P-450 in rat liver treated with phenobarbital or with chloramphenicol were almost in parallel with the blood levels of normustard-like substances. The above data suggest that, in the chemotherapy with anti-cancer drugs, inductive or inhibitory effect of the drugs on microsomal drug-metabolizing enzymes should be taken into consideration.
