注射用盐酸苯达莫司汀在肿瘤患者体内的药动学研究

Pharmacokinetics of bendamustine hydrochloride in cancer patients

目的：评价注射用盐酸苯达莫司汀在肿瘤患者体内的药动学特征。方法：10例受试者接受120mg·m^-2盐酸苯达莫司汀慢速静脉滴注，以苯达莫司汀中间体为内标，采用高效液相法（HPLC）测定给药后血浆药物浓度，以DAS2．1软件进行药动学参数的计算分析。结果：血药浓度在5～10000ng·mL^-1剂量范围内线性关系良好。静脉滴注120mg·m^-2盐酸苯达莫司汀（4h），平均消除半衰期（t1/2）、达峰浓度（Cmax）、达峰时间（Tmax）及血药浓度-时间曲线下面积（AUC_0-t）分别为（0．389±0．052）h、（2．2±0．8）μg·mL^-1、（2．9±1．2）h、（6．7±1．8）·g·mL^-1·h。受试者在研究期间未发生Ⅲ度及以上不良反应。结论：本研究建立的检测方法简单快速，试剂消耗少，准确度及精密度良好，适合盐酸苯达莫司汀人体药动学研究。单次静脉注射盐酸苯达莫司汀，受试者耐受良好。

Objective： To evaluate the pharmacokineties of bendamustine hydroehloride in cancer patients. Methods ： Ten cancer patients received intravenous bendamustine hydroehloride （ 120 mg· m^-2 ）. The plasma con- centrations of bendamustine hydrochloride were determined by high-performance liquid chromatography （ HPLC ）. DAS 2. 1 software was applied to calculate and assess the plasma concentration-time data. Results： The plasma concentrations of bendamustine increase proportionally over the dose range of 5 to 10 000 ng· mL^-1. After intrave- nous injection of 120 mg· m^-2 bendamustine hydroehloride to the subjects over 4 hours, the mean value of t1/2 was （0. 389 ±0.052） h, Cmax was （2.2 ±0.8） ng·m^-1, and Tmax was （2.9 ± 1 .2） h. The AUCo-t of bendamustine hydroehloride was （6.7 ± 1.8） μg· mL^- 1 · h. No grade 3 or grade 4 toxicity was observed during the study. Con- clusion： A simple, rapid, and high cost-effective HPLC method for bendamustine hydrochloride quantification in human plasma has been developed and validated. All the participants are well-tolerated throughout the study.