Phà © nobarbitalEffects on Cyclophosphamide Pharmacokinetics in Man 1

Plasma concentrations and urinary excretion rates of cyclophosphamide and its total metabolites were measured after i.v. administration of 500to 1000-mg doses of radiolabeled cyclophosphamide to four patients. The data obtained before and after phénobarbital treatment were analyzed pharmacokinetically with the use of a two-compart ment open model. Phénobarbital had no quantitatively important effects on the distribution and renal excretion of cyclophosphamide. The rate of biotransformation of the inactive precursor to its total metabolites was increased 2to 3-fold by phénobarbital. However, because biotransformation is the predominant pathway of cyclophosphamide disposition, the total quantity of metabolites formed was only increased slightly by phénobarbital. These observations, together with comprehensive data in the literature showing that phénobarbital has little effect on the chemotherapeutic properties of cyclophosphamide in several animal tumor systems, indicate that phénobarbital treatment should modify only slightly the efficacy and toxicity of cyclophosphamide in man.