Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse
| Autor: | Y. M. Peng, R. F. Struck, H. S. Chen, D. S. Alberts |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Male
Cancer Research Cyclophosphamide medicine.medical_treatment Pharmacology Mice Pharmacokinetics medicine Animals Drug Interactions heterocyclic compounds Chemotherapy Leukemia Experimental Chemistry Therapeutic effect Metabolism Drug interaction Phosphoramide Mustard Kinetics Oncology Mice Inbred DBA Phenobarbital cardiovascular system Phosphoramide Mustards Chromatography Thin Layer Research Article medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1978.204 |
| Popis: | 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, (10(6) cells i.p.) was administered to all mice on Day 8, and 2 days later both groups of mice were given i.p. CPA (200 mg/kg) with 14C-CPA (0.2 muCi 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 x 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 CPA 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. |
| Databáze: | OpenAIRE |
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