title: Effect of phenobarbital on cyclophosphamide cytotoxic activity and pharmacokinetics in mice.
abstract: The interaction between cyclophosphamide (CPA) and phenobarbital (PB) was investigated in B6D2F1 mice, checking both the antileukemic and immunosuppressive activity together with the serum levels of CPA and its metabolites. A reduced cytotoxic activity of CPA has been observed when PB is given for 2 days before CPA and an interval of at least 6 hours elapses between the last treatment of PB and the administration of CPA. On the contrary, when PB is given simultaneously with CPA for 2 or 4 consecutive days, an increased antileukemic activity of CPA occurs. In the experimental condition where PB decreases the activity of CPA, serum levels of CPA, assayed by means of a new specific gas-chromatographic method, and of its NBP-alkylating metabolites, indicate that this effect may be explained on a pure pharmacokinetic basis. However, for the situation where an increased effect of CPA was observed under the influence of PB, pharmacokinetic data did not provide a clear explanation.
mesh_terms: D000818:Animals; D001681:Biological Assay; D001711:Biotransformation / Q000187:drug effects; D003520:Cyclophosphamide / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000494:pharmacology*
chemical_list: D003520:Cyclophosphamide; D010634:Phenobarbital