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目的:研究奥沙利铂(L-OHP)用于消化系统肿瘤患者两种给药方案下静脉输注不同剂量时,血浆游离铂、血浆总铂的药动学情况,监测体内血浆蛋白结合铂的变化。方法:建立HPLC-UV检测方法,运用衍生化法分别测定血浆游离铂和总铂浓度,绘制药-时曲线,计算两组药动学参数及血浆蛋白结合参数。结果:L-OHP在0.1～8mg·L-1范围内衍生物浓度与峰面积呈良好的线性关系,游离铂相对回收率和血浆总铂相对回收率分别为91.83%(RSD为9.60%)和91.79%(RSD为9.94%)。两种给药剂量下,48h内药物血浆中均表现为较高血浆蛋白结合率,并随时间延长呈上升趋势,低剂量组较高剂量组更为明显;两种剂量测定单次给药后L-OHP的药动学参数,游离铂组间α、V1、AUC(0-t)、K10、MRT(0-t)间差异有显著性;血浆总铂组间α、β、t1/2β、V1、AUC(0-t)、AUC(0-∞)、K21、MRT(0-t)、MRT(0-∞)间差异有显著性。结论:该测定方法准确、快速、便捷;L-OHP不同剂量用于治疗消化系统肿瘤时均表现出高血浆蛋白结合率;L-OHP药动学参数与剂量相关,单次给药130mg·m-2更可充分发挥药物作用。
OBJECTIVE: To study the pharmacokinetics of plasma free platinum and plasma total platinum when intravenous infusion of oxaliplatin (L-OHP) is administered to patients with digestive system tumors under intravenous infusion of different doses and to monitor plasma protein binding to platinum The change. Methods: The HPLC-UV method was established. The concentration of free platinum and total platinum in plasma were determined by derivatization method. The pharmacokinetic parameters and the plasma protein binding parameters were calculated. Results: The concentration of L-OHP in the range of 0.1-8 mg · L-1 showed a good linear relationship with the peak area. The relative recovery of free platinum and plasma total platinum were 91.83% (RSD 9.60%) and 91.79% (RSD 9.94%). Under the two administration doses, the plasma protein binding rate in the plasma of the drug for 48h showed a tendency of increasing with the prolongation of time. The low dose group was more obvious than the high dose group. The pharmacokinetic parameters of L-OHP were significantly different between the groups of free platinum, α, V1, AUC (0-t), K10 and MRT There was significant difference between V1, AUC (0-t), AUC (0-∞), K21, MRT (0-t) and MRT (0-∞) Conclusion: The method is accurate, rapid and convenient. The L-OHP at different dosages shows high plasma protein binding rate in the treatment of digestive system tumors. The pharmacokinetic parameters of L-OHP are dose-dependent. The single dose of 130 mg · m -2 can give full play to the role of drugs.