This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jao, J. Y. Articles by Cohen, J. L. Search for Related Content PubMed PubMed Citation Articles by Jao, J. Y. Articles by Cohen, J. L.

Phenobarbital Effects on Cyclophosphamide Pharmacokinetics in Man¹

Oncology Division, Department of Medicine, Lemuel Shattuck Hospital, Tufts University School of Medicine, Boston, Massachusetts 02130 [J. Y. J., J. L. C.], and Section of Clinical Pharmacology, Veteran's Administration Hospital, Boston, Massachusetts [W. J. J.]

Plasma concentrations and urinary excretion rates of cyclophosphamide and its total metabolites were measured after i.v. administration of 500- to 1000-mg doses of radiolabeled cyclophosphamide to four patients. The data obtained before and after phenobarbital treatment were analyzed pharmacokinetically with the use of a two-compartment open model. Phenobarbital 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 2- to 3-fold by phenobarbital. However, because biotransformation is the predominant pathway of cyclophosphamide disposition, the total quantity of metabolites formed was only increased slightly by phenobarbital. These observations, together with comprehensive data in the literature showing that phenobarbital has little effect on the chemotherapeutic properties of cyclophosphamide in several animal tumor systems, indicate that phenobarbital treatment should modify only slightly the efficacy and toxicity of cyclophosphamide in man.

¹ This work was supported in part by Research Grants CA-12924-01 and CA-10709-02 from the National Cancer Institute, USPHS.

Received 6/26/72. Accepted 9/11/72.

This article has been cited by other articles:

				S. Gerbal-Chaloin, J.-M. Pascussi, L. Pichard-Garcia, M. Daujat, F. Waechter, J.-M. Fabre, N. Carrère, and P. Maurel Induction of CYP2C Genes in Human Hepatocytes in Primary Culture Drug Metab. Dispos., March 1, 2001; 29(3): 242 - 251. [Abstract] [Full Text]