Effect of phenobarbital on cyclophosphamide metabolism in rats.
1. The pharmacokinetics of cyclophosphamide and its alkylating metabolites have been studied in rats whose liver microsomal enzymes had been induced by phenobarbital pre-treatment. 2. Serum levels of cyclophosphamide were determined using a new g.l.c. method. The half-life of cyclophosphamide in blood of rats pre-treated with phenobarbital was shorter than in control rats. This change is closely related to higher rates of production of p-nitrobenzylpyridine-positive alkylating metabolites of cyclophosphamide, which in turn is followed by their more rapid disappearance from the circulation. 3. Urinary excretion reflects this situation; lower amounts of cyclophosphamide and higher concentrations of its alkylating metabolites are present in the urine of phenobarbital-treated rats. 4. Perfusion of livers isolated from phenobarbital-pre-treated rats confirmed the results in vivo. With this preparation, too, disappearance of cyclophosphamide was more rapid and formation of its alkylating metabolites was accelerated after phenobarbital treatment.
D000477:Alkylating Agents / Q000378:metabolism; D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats
D000477:Alkylating Agents; D003520:Cyclophosphamide; D010634:Phenobarbital