Effects of co-administraton of neferine and doxorubicin on the pharmacokinetics of doxorubicin  

甲基莲心碱对阿霉素药动学影响（英文）

作　　者：薛清丹 鞠爱霞[1] 康宇红[1] 郑春雨[1] 李秋红[1] 

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《Journal of Chinese Pharmaceutical Sciences》2015年第4期225-230,共6页中国药学（英文版）

基　　金：The Scientific Research Fund Project of Heilongjiang University of Chinese Medicine(Grant No.201420)

摘　　要：Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serious cardio-cytotoxic effects. The aim of this study was to investigate the effect of neferine, a bisbenzylisoquinoline alkaloid extracted from the green embryo in the mature lotus seed, on the pharmacokinetics of doxorubicin. The levels of doxorubicin in plasma and tissues were measured using the high performance liquid chromatography（HPLC） method. The chromatographic separation was completed on a reversed-phase C18 column using acetonitrile–phosphate buffer（30：70, v/v） as the mobile phase at a flow rate of 1 mL /min and ultraviolet detection wave length was set at 233 nm. The pharmacokinetic study found that the co-administration of neferine and doxorubicin significantly affected the pharmacokinetics of doxorubicin. There were evident changes in area under the curve（AUC）, clearance（CL） and t1/2β in group of pretreatment neferine as compared with those in group treated with doxorubicin alone. Tissue distribution analysis showed that the concentrations of doxorubicin distributed to heart, liver and kidney were statistically significant higher in group of pretreatment with neferine plus doxorubicin than those in the doxorubicin alone-group at 0.5 h and 2 h after drug administration, respectively. While the doxorubicin concentrations in spleen and lung drug were slightly increased in the group of pretreatment with neferine plus doxorubicin as compared to that of group of doxorubicin alone, the difference between two groups were not statistically significant. Therefore, the dose of doxorubicin needs to be taken into consideration when it is administrated in combination with neferine.阿霉素是一种蒽环类广谱抗肿瘤药物,用于治疗白血病、肝癌,乳腺癌等实体肿瘤。本研究的目的是探讨甲基莲心碱对阿霉素药动学影响。通过高效液相色谱法测定阿霉素的血浆和组织中的药物浓度,运用C18反相色谱柱进行分离,流动相是乙腈:磷酸水溶液比例为30:70,流速为1 m L/min,检测波长为233 nm。药代动力学研究发现给予甲基莲心碱明显影响阿霉素的药动学。与对照组比较甲基莲心碱预处理组的AUC,CL和t1/2β明显改变。组织分布表明:心脏、肝脏和肾脏中的药物浓度在0.5和2小时明显高于阿霉素单独组药物浓度。甲基莲心碱预处理组与阿霉素组比较脾脏和肺脏药物浓度轻微的增加,但没有显著性差异。因此,当阿霉素与甲基莲心碱联用时应该考虑阿霉素的给药剂量。

关 键 词：Neferine Doxorubicin Pharmacokinetics HPLC method Anthracycline anti-neoplastic drugs 

分 类 号：R969.1[医药卫生—药理学]