The effect of phenobarbital on cyclophosphamide antitumor activity

David S Alberts, T. Van Daalen Wetters

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The authors have used the spleen colony assay system and survival duration studies in male DBA/2 mice with P388 leukemia to study the effects of microsomal enzyme induction by phenobarbital on the antileukemic activity and bone marrow toxicity of cyclophosphamide. Phenobarbital drinking water (0.5 mg/ml) was given for 7 days prior to cyclophosphamide (10 to 200 mg/kg i.p.). Average daily phenobarbital intake per mouse was 1.25 mg (equivalent to 4 mg/kg/day human dosage). Dose response curves with and without phenobarbital pretreatment showed a constant 90% (1 log) reduction in the toxicity of cyclophosphamide to leukemic colony forming units, whereas enzyme induction had no effect on the toxicity of the drug to normal bone marrow colony forming units. Parallel survival studies confirmed the 1 log diminution in the antileukemic activity of cyclophosphamide in phenobarbital pretreated mice. This phenobarbital induced change in the antitumor activity of cyclophosphamide appears explainable on a pharmacokinetic basis. The Friedman and Boger assay for plasma alkylating metabolites showed that the reduction in the area under the plasma metabolite curve caused by enzyme induction exactly predicted the observed reduction in cyclophosphamide antitumor effect.

Original languageEnglish (US)
Pages (from-to)2785-2789
Number of pages5
JournalCancer Research
Volume36
Issue number8
StatePublished - 1976

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Phenobarbital
Cyclophosphamide
Enzyme Induction
Stem Cells
Bone Marrow
Leukemia P388
Inbred DBA Mouse
Survival
Drug-Related Side Effects and Adverse Reactions
Drinking Water
Spleen
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The effect of phenobarbital on cyclophosphamide antitumor activity. / Alberts, David S; Van Daalen Wetters, T.

In: Cancer Research, Vol. 36, No. 8, 1976, p. 2785-2789.

Research output: Contribution to journalArticle

Alberts, DS & Van Daalen Wetters, T 1976, 'The effect of phenobarbital on cyclophosphamide antitumor activity', Cancer Research, vol. 36, no. 8, pp. 2785-2789.
Alberts, David S ; Van Daalen Wetters, T. / The effect of phenobarbital on cyclophosphamide antitumor activity. In: Cancer Research. 1976 ; Vol. 36, No. 8. pp. 2785-2789.
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