吡柔比星单次或分次给药对药代动力学和药物不良反应影响的研究  

Influence of different administration methods of pirarubicin (THP) on its pharmacokinetics and toxicity

作　　者：张晓静[1] 张频[1] 徐兵河[1] 董英[1] 叶敏[2] 朱珠[2] 陈哲[3] 王佳玉[1] 宋岩[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院内科,北京100021 [2]中国医学科学院北京协和医院药剂科临床药理研究室,北京100730 [3]中国医学科学院北京协和医学院肿瘤医院药剂科,北京100021

出　　处：《癌症进展》2008年第4期396-401,共6页Oncology Progress

摘　　要：目的比较吡柔比星(THP)单次或分次给药对临床药代动力学参数和不良反应的影响,以及药代动力学和不良反应间的相关性。方法20例乳腺癌患者根据术后分期、年龄分为2组,分别接受THP60mg/m^2,d1或THP30 mg/m^2,d1、d2与环磷酰胺(CTX)联合的两药化疗。高效液相色谱法(HPLC)测定THP血药浓度;WinNonlin4.0程序进行药动学房室模型数据拟合和参数计算;按照CTCAE3.0标准评价近期常见不良反应。结果药代动力学结果显示两组均有8例药时曲线表现为典型的三室模型,2例符合二室模型。两次给药组的心脏不适症状和心电图异常的发生率均显著低于单次给药组。血液学不良反应明显,两组基本一致,食欲不振、恶心、呕吐等胃肠道不良反应多为Ⅰ～Ⅱ度,两组间无明显差异。结论药代结果显示两组均以三室模型为主。两次给药组急性心脏不良反应明显较单次给药组降低,血液学不良反应、胃肠道不良反应两组相似。To explore the influence of different administration methods of pirarubicin （THP） on pharmacokinetics and toxicity. Method Totally 20 patients with resectable breast cancer were treated with pirarubicin - containing combination chemotherapies, including THP 60mg/m^2, iv, dl or THP 30 mg/m^2, iv, d1, d2. The THP concentrations in human plasma were determined by a high - performance liquid chromatography （HPLC）. The modelling data were performed with a compartment pharmacokinetic modelling program （ WinNonlin 4. 0）. The toxicities were evaluated by CTCAE 3.0 index. Results The pharmacokinetic results showed wide inter-individual variation. In each group 8 patients were best described by a typical three-compartment model, and 2 patients were best described by a typical two-compartment model. The incidence of cardiac single administration group and electrocardiographic abnormality were significantly lowerin the than in the twice administration group. The hematologic toxicities were obvious and were similar between two groups. The gastrointestinal toxicities, hematologic toxicities, alopecie and stomatitis were minor and also similar between two groups. The AUC and Cmax values of the twice administration group were significatry lower than single administration group. The acute cardiac toxicities in the twice administration group were significantly lower than in the single administration group. There were no differences in gastrointestinal, hematologic and alopecie toxicities between the two groups. Conclusion The twice administratim method of THP has superior cardiac toxicity than the single admistration method, although their hematologic and alopecie toxicities are similiar.

关 键 词：吡柔比星 单次给药 两次给药 药代动力学 不良反应 

分 类 号：R730.53[医药卫生—肿瘤]