title: Effect of phenobarbital on cyclophosphamide metabolism in rats.
abstract: 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.
mesh_terms: 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
chemical_list: D000477:Alkylating Agents; D003520:Cyclophosphamide; D010634:Phenobarbital