Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy
Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy
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DOI：
10.1186/1471-2407-7-197
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发表时间：
2007-10-23
期刊：
影响因子：
3.8
通讯作者：
Olsen, Harald
中科院分区：
文献类型：
--
作者：
Brunsvig, Paal Fr;Andersen, Anders;Olsen, Harald
背景：以前的多西他赛药代动力学研究大多采用每周3次(75 mg/m(2)和100 mg/m(2))或每周方案(35-40 mg/m(2))。然而，每周20 mg/m(2)多西紫杉醇的药代动力学和放射增敏效果尚未得到很好的表征。方法：34例非小细胞肺癌(NSCLC)患者，19例接受每周100 mg/m(2)多西紫杉醇单次治疗，15例每周接受20 mg/m(2)多西紫杉醇每周联合放疗。建立了一种新的多西紫杉醇血药浓度测定方法，可将多西紫杉醇的血药浓度测定到纳摩尔水平。在本研究中，我们证明了多西紫杉醇20 mg/m(2)给药后72小时的血药浓度中位数为3 nM。结论：多西紫杉醇的药代动力学具有个体差异大的特点，在某些时间点，20 mg/m(2)和100 mg/m(2)的多西紫杉醇的血药浓度存在重叠。这些结果的外推表明，放射增敏的多西紫杉醇浓度可能存在长达1周，因此支持每周使用20 mg/m(2)的多西紫杉醇。
Background: Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m(2) and 100 mg/m(2)) or weekly regimens (35-40 mg/m(2)). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m(2) docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m(2) regimen.Methods: Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m(2) docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m(2) docetaxel weekly with concurrent radiotherapy. A newly developed HPLC method was used for measuring docetaxel levels, capable of quantifying docetaxel in plasma down to the nanomolar level.Results: The HPLC method showed detectable concentrations of docetaxel in plasma even after 72 hours. In the present study we have demonstrated that median docetaxel plasma levels of 3 nM can be obtained 72 hours after a dose of 20 mg/m(2).Conclusion: The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m(2) and 100 mg/m(2) docetaxel were overlapping. Extrapolation of these results indicates that radio sensitizing docetaxel concentrations may be present for as long as 1 week, thus supporting the use of 20 mg/m(2) weekly docetaxel.