Struck R F, Alberts D S
Cancer Treat Rep. 1984 May;68(5):765-70.
Blood levels of cyclophosphamide (CPA) and its alkylating metabolites in mice were determined after iv or oral administration of a 200-mg/kg dose of radiolabeled CPA. Individual metabolites (4-hydroxy-CPA, 4-keto-CPA, alcophosphamide , dechloroethyl -CPA, carboxyphosphamide , and phosphoramide mustard) were isolated from blood by solvent extraction and by thin-layer chromatography. Area-under-the-blood-decay-curve (AUC) values were determined for CPA and its alkylating metabolites to provide a basis for comparison of systemic exposure by iv or oral treatment. The total AUC values for alkylating metabolites of CPA was observed to be greater after iv administration, and AUC values for each of the individual metabolites were greater after iv treatment, except for the minor metabolite alcophosphamide . The methods in this study have been applied to one patient to date and will be used in future studies with other patients to determine relative AUC values for the oncolytic CPA metabolites 4-hydroxy-CPA and phosphoramide mustard.
给小鼠静脉注射或口服200 mg/kg剂量的放射性标记环磷酰胺（CPA）后，测定其血液中环磷酰胺及其烷基化代谢物的水平。通过溶剂萃取和薄层色谱法从血液中分离出各个代谢物（4-羟基-CPA、4-酮基-CPA、醛磷酰胺、去氯乙基-CPA、羧基磷酰胺和磷酰胺氮芥）。测定CPA及其烷基化代谢物的血药浓度-时间曲线下面积（AUC）值，为比较静脉注射或口服治疗后的全身暴露情况提供依据。观察到静脉注射后CPA烷基化代谢物的总AUC值更高，除了次要代谢物醛磷酰胺外，静脉注射治疗后各个代谢物的AUC值也更高。本研究中的方法迄今已应用于一名患者，未来将用于其他患者的研究，以确定溶瘤性CPA代谢物4-羟基-CPA和磷酰胺氮芥的相对AUC值。
