苯巴比妥对小鼠血浆中环磷酰胺及其代谢产物水平的影响。
Effect of phenobarbital on plasma levels of cyclophosphamide and its metabolites in the mouse.
作者信息
Alberts D S, Peng Y M, Chen H S, Struck R F
出版信息
Br J Cancer. 1978 Aug;38(2):316-24. doi: 10.1038/bjc.1978.204.
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.
我们使用放射性标记的环磷酰胺（CPA）结合薄层色谱法，研究了对照动物和苯巴比妥处理动物中各代谢物及未变化的CPA的定量药代动力学差异。在第0天，一组开始饮用含苯巴比妥的水，另一组继续饮用常规酸性水。在第8天给所有小鼠腹腔注射P388白血病细胞（10⁶个细胞），2天后两组小鼠腹腔注射CPA（200mg/kg）及¹⁴C-CPA（每只小鼠0.2μCi）。在注射CPA后5 - 60分钟，每组取10只小鼠处死，收集血液用于检测血浆中母体化合物和代谢物。苯巴比妥预处理分别使CPA和磷酰胺氮芥的浓度 - 时间曲线下面积（CXT）降低了66%以上和27%以上。假设磷酰胺氮芥既是CPA的最终细胞毒性形式又是血液转运形式，那么苯巴比妥使CPA减少可能预示着治疗效果降低。本研究中的检测方法未来将用于确定这种潜在药物相互作用在人体中的重要性。
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