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

  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，AUC_0~168h分别为（7.5±2.5）、（15.2±4.0）、（34.8±9.7）μg·h·mL-1；消除半衰期t_1/2分别为（27.2±9.5）、（27.2±6.5）、（31.4±5.6）h。AUC_0~168h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。 

Pharmacokinetic study of palonosetron hydrochloride in healthy volunteers

  Objective   To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers.  Methods   Thirty-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 AUC_0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t_1/2 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.  Conclusion   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 pharmacokinetics over the the dose range of 0.125 mg to 0.5 mg.