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目的:研究多西他塞(泰索帝)在与顺铂联合用药情况下的药动学特征,确定和推荐Ⅱ期临床试验的给药方案。方法:选择晚期转移ⅢB或Ⅳ期非小细胞肺癌(NSCLC)患者15例,分成4组,分别按25,30,35,40mg·m-2剂量,每周1次方案给药,在每28d中的d1,8,15静注给药,4个剂量组均按75mg·m-2固定剂量给予顺铂。在第1周期的d1和d15给药前即刻,静注30min给药结束即刻,给药结束后10,30,45,60,90min及3,5,8,12,24h分别采血,用LC/MS/MS测定血药浓度。用WinNonlin软件按恒速静脉输注给药的三室模型进行分析并计算相关药动学参数。经对数转换的药动学参数包括剂量归一化的AUCN,Cmax和Cl,用SAS Proc混合程序进行检验。结果:在给药d1,当剂量从25增加到40mg·m-2时,平均AUC值从(1 393±288)增加到(1 968±757)μg·h·L-1;d15平均AUC值从(1 423±149)增加到(1 751±564)μg·h·L-1。在给药d1和d15,CmaxN,AUCN及Cl值均无显著性差异。结论:多西他塞静脉给药后Cmax和AUC值与剂量成比例增加,而Cl值与剂量水平无关,其药动学不受合用顺铂的影响。
OBJECTIVE: To study the pharmacokinetics of docetaxel (Taxotere) in combination with cisplatin, and to determine and recommend the dosing regimen for Phase II clinical trial. Methods: Fifteen patients with advanced stage ⅢB or Ⅳ non-small cell lung cancer (NSCLC) were enrolled and divided into 4 groups. The patients were treated with 25, 30, 35 and 40 mg · m-2 respectively once a week. In the d1,8,15 intravenous administration, four dose groups were given a fixed dose of 75mg · m-2 cisplatin. Immediately before the d1 and d15 administration in the first cycle, 30 minutes after the end of intravenous injection, 10, 30, 45, 60, 90 minutes and 3,5,8, 12 and 24 hours after the end of the administration, MS / MS determination of plasma concentration. The WinNonlin software was used to analyze the three-compartment model of constant-dose intravenous infusion and to calculate the relevant pharmacokinetic parameters. Logarithmic conversion pharmacokinetic parameters include dose-normalized AUCN, Cmax and Cl, tested using the SAS Proc Mix procedure. Results: The average AUC increased from (1 393 ± 288) to (1 968 ± 757) μg · h · L -1 at d 1 when the dose was increased from 25 to 40 mg · m -2. The mean AUC of d15 Increased from (1 423 ± 149) to (1 751 ± 564) μg · h · L -1. There was no significant difference in CmaxN, AUCN and Cl between d1 and d15. CONCLUSIONS: The values of Cmax and AUC increased in proportion to the dose of docetaxel after intravenous administration, whereas the value of Cl did not correlate with the dose level. The pharmacokinetics of cisplatin was not affected by cisplatin.