Phenobarbital effects on cyclophosphamide pharmacokinetics in man.
Phenobarbital effects on cyclophosphamide pharmacokinetics in man.
复制标题
苯巴比妥对人类环磷酰胺药代动力学的影响。
作者：
J. Jao;W. Jusko;J. Cohen
总结：4例患者接受500- 1000 mg放射性标记环磷酰胺静脉给药后，测定了环磷酰胺及其总代谢产物的血浆浓度和尿排泄率。使用二室开放模型对苯巴比妥治疗前后的数据进行药代动力学分析。苯巴比妥对环磷酰胺的分布和肾脏排泄没有重要的影响。苯巴比妥使无活性前体向其总代谢产物的生物转化率增加2- 3倍。然而，由于生物转化是环磷酰胺处置的主要途径，因此苯巴比妥仅略微增加形成的代谢物总量。这些观察结果以及文献中显示苯巴比妥对环磷酰胺在几种动物肿瘤系统中的化疗特性几乎没有影响的综合数据表明，苯巴比妥治疗仅会轻微改变环磷酰胺在人体中的疗效和毒性。
Summary Plasma concentrations and urinary excretion rates of cyclophosphamide and its total metabolites were measured after i.v. administration of 500- to 1000-mg doses of radiolabeled cyclophosphamide to four patients. The data obtained before and after phenobarbital treatment were analyzed pharmacokinetically with the use of a two-compartment open model. Phenobarbital had no quantitatively important effects on the distribution and renal excretion of cyclophosphamide. The rate of biotransformation of the inactive precursor to its total metabolites was increased 2- to 3-fold by phenobarbital. However, because biotransformation is the predominant pathway of cyclophosphamide disposition, the total quantity of metabolites formed was only increased slightly by phenobarbital. These observations, together with comprehensive data in the literature showing that phenobarbital has little effect on the chemotherapeutic properties of cyclophosphamide in several animal tumor systems, indicate that phenobarbital treatment should modify only slightly the efficacy and toxicity of cyclophosphamide in man.