盐酸帕洛诺司琼注射液在健康受试者体内的药代动力学研究

摘要

目的：评价盐酸帕洛诺司琼注射液在健康受试者体内的药动学特征。方法：31例健康受试者分成3组，单次静脉注射盐酸帕洛诺司琼剂量分别为0.125，0.25和0.5 mg。采用超高效液相-串联质谱法（UPLC-MS/MS）测定人血浆中帕洛诺司琼浓度，采用DAS 2.1药动学软件进行药动学参数的分析和计算。结果：单剂量静脉注射0.125，0.25和0.5 mg的盐酸帕洛诺司琼注射液后，AUC0～168h分别为（7.5±2.5）、（15.2±4.0）、（34.8±9.7）μg·h·mL-1；消除半衰期t1/2分别为（27.2±9.5）、（27.2±6.5）、（31.4±5.6）h。AUC0～168h与剂量呈正相关，相关系数为0.998。受试者在研究期间未发生重度以上不良事件。结论：本研究建立的检测方法简单、快速、准确、灵敏度高，适合盐酸帕洛诺司琼人体药代动力学研究。单次静脉注射盐酸帕洛诺司琼后，受试者耐受良好。在0.125～0.5 mg剂量范围内，帕洛诺司琼在健康受试者体内表现为线性药动学特征。%Objective: To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers. Methods: Thir-ty-one healthy volunteers were grouped into three palonosetron hydrochloride dosage regimens of 0.125, 0.25, and 0.5 mg. The plasma concentrations of palonosetron were determined by ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). DAS 2.1 software was applied to assess the plasma concentration-time data. Results:After intravenous injection of 0.125, 0.25, and 0.5 mg palonosetron to the subjects, the AUC0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t1/2 values were (27.2±9.5), ( 27.2±6.5), and (31.4±5.6) h. Palonosetron exposure increased proportionally with the dose range of 0.125 mg to 0.5 mg. The correlation coefficient was 0.998. No grade 3 or grade 4 toxicity was observed during the study. Con-clusion:A rapid, sensitive, and selective UPLC-MS/MS method for palonosetron quantification in human plasma was developed and validated. All the participants indicated high tolerance throughout the study. Our data showed that palonosetron exhibits linear pharma-cokinetics over the the dose range of 0.125 mg to 0.5 mg.