Pharmacokinetics of oxaliplatin in humans
Pharmacokinetics of oxaliplatin in humans
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DOI：
10.1385/mo:19:4:261
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发表时间：
2002-01-01
期刊：
影响因子：
3.4
通讯作者：
Yachnin, J
中科院分区：
文献类型：
--
作者：
Ehrsson, H;Wallin, I;Yachnin, J
奥沙利铂是一种新型的铂配合物，用于治疗转移性结直肠癌。在10例接受85 mg/m2奥沙利铂输注时间为2 h的患者中评价了血液中奥沙利铂游离部分的药代动力学。在输注期间和输注后采集血样，并立即置于冰上。样品离心超滤，超滤液中奥沙利铂的浓度通过液相色谱法结合柱后衍生法测定。在给药前即刻采集患者血液，测定体外降解速率，最大血药浓度（C-max）和终末半衰期（t（1/2））分别为1.44 +/- 0.20（SD）mug/mL和14.1 min（范围：10.2-24.5）。血药浓度-时间曲线下面积（AUC）、清除率（CL）和分布容积（V-ss）分别为（平均SD）161 +/- 22 μ g min/mL、32.1 +/- 4.2 L/h/m2和0.26 +/- 0.06 L/kg。奥沙利铂在患者体内的清除率与其在全血中的降解率之间存在显著相关性（r = 0.746; p = 0.017）。奥沙利铂的消除半衰期较短，这与先前报道的通过分析血浆和超滤液中的铂含量获得的消除半衰期形成鲜明对比。体内和体外数据之间的相关性表明，全血中的降解对药物的消除起作用。
Oxaliplatin is a novel platinum complex used for the treatment of metastatic colorectal carcinoma. The pharmacokinetics of the free fraction of oxaliplatin in blood were evaluated in 10 patients given 85-mg/m(2) of oxaliplatin using an infusion time of 2 h. Blood samples were collected during and after the infusion and immediately placed on ice. The samples were ultrafiltrated centripetally and the concentration of oxaliplatin in the ultrafiltrate was determined by liquid chromatography in combination with postcolumn derivatization. The in vitro degradation rate was determined in blood from the patients taken immediately before drug administration.The maximal blood concentration (C-max) and terminal half-life (t(1/2)) were 1.44 +/- 0.20 (SD) mug/mL and 14.1 min (range: 10.2-24.5), respectively. The area under the blood concentration time curve (AUC), clearance (CL), and distribution volume (V-ss) were (means SD) 161 +/- 22 mug min/mL, 32.1 +/- 4.2 L/h/m(2), and 0.26 +/- 0.06 L/kg, respectively. There was a significant correlation between the clearance of oxaliplatin in the patients and the degradation rate in whole blood (r = 0.746; p = 0.017).Oxaliplatin has a short elimination half-life, which is in a sharp contrast to previously reported elimination half-lives obtained by analysis of the platinum content in plasma and ultrafiltrate. The correlation between in vivo and in vitro data suggests that the degradation in whole blood plays a role for the elimination of the drug.