Factors affecting pharmacokinetic variability following doxorubicin and docetaxel-based therapy
Factors affecting pharmacokinetic variability following doxorubicin and docetaxel-based therapy
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DOI：
10.1016/j.ejca.2003.12.026
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发表时间：
2004-05-01
影响因子：
8.4
通讯作者：
Baker, SD
中科院分区：
文献类型：
--
作者：
Rudek, MA;Sparreboom, A;Baker, SD
目前抗癌药物的给药策略导致个体间药动学差异很大。在此，我们探讨了年龄、体型、辅助药物、剂量、输液时间和性别对243名个体患者阿霉素和多西紫杉醇清除量的影响。患者接受阿霉素(n=110)或多西他赛(n=152)作为单一治疗或联合化疗方案。平均值(+/-S.D.)阿霉素组清除量为63.6±22.7L/h，多西紫杉醇为42.8±14.9L/h。体表面积(BSA)的正常化仅减少了1.7%的个体间变异性。阿霉素清除量在剂量为50 mg/m(2)或与环磷酰胺合用时显著降低。身体大小的上限与两种药物清除量的增加有关，而年龄对清除量的影响并不一致。总体而言，这些发现表明，在阿霉素和多西紫杉醇的常规剂量策略中，除了BSA之外，还应该考虑纳入变量。(C)2004爱思唯尔有限公司。保留所有权利。
Current dosing strategies for anticancer drugs result in wide interindividual pharmacokinetic variability. Here, we explored the influence of age, body size, concomitant drugs, dose, infusion duration, and sex on the clearance for doxorubicin and docetaxel in 243 individual patients. Patients received doxorubicin (n = 110) or docetaxel (n = 152) as monotherapy or in combination chemotherapy regimens. The mean (+/-S.D.) clearance was 63.6 +/- 22.7 L/h for doxorubicin and 42.8 +/- 14.9 L/h for docetaxel. Normalisation for body surface area (BSA) reduced the interindividual variability by only < 1.7%. Doxorubicin clearance was significantly reduced when administered at doses > 50 mg/m(2) or in combination with cyclophosphamide. Upper extremes of body size were associated with increased clearance for both drugs, whereas no consistent effect of age on clearance was discerned. Overall, these findings suggest that incorporation of variables in addition to BSA should be considered in routine dosing strategies for doxorubicin and docetaxel. (C) 2004 Elsevier Ltd. All rights reserved.