Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse

D. S. Alberts, Y. M. Peng, H. S. Chen, R. F. Struck

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We have studied the quantitative pharmacokinetic differences of individual metabolites and unchanged cyclophosphamide (CPA) in control and phenobarbital-treated animals, using radiolabelled CPA together with thin-layer chromatography. On Day 0, one group was started on phenobarbital drinking water and one group stayed on regular acid water. P388 leukaemia, (106 cells i.p.) was administered to all mice on Day 8, and 2 days later both groups of mice were given i.p. CPA (200mg/kg) with 14C-CPA(0.2µCi Per mouse). At 5-60 min after CPA administration, groups of 10 mice were killed and their blood collected for assay of parent compound and metabolites in plasma. Phenobarbital pretreatment reduced CPA and phosphoramide mustard CXT (concentration × time) by 66+% and 27+%, respectively. Assuming that phosphoramide mustard is both the ultimate cytotoxic form of CPA and the blood-transport form, the reduction of CXT by phenobarbital would predict a decreased therapeutic effect. The assay methods in this study will be used in the future to determine the importance of this potential drug interaction in man.

Original languageEnglish (US)
Pages (from-to)316-324
Number of pages9
JournalBritish journal of cancer
Volume38
Issue number2
DOIs
StatePublished - Aug 1978
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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