达沙替尼片在中国健康人体内的药动学

Pharmacokinetics of dasatinib tablets in Chinese healthy volunteers

目的：建立人血浆中达沙替尼浓度的液-质联用（LC-MS/MS）测定法,研究达沙替尼片在中国健康人体内的药动学。方法：24例男性健康受试者单剂量空腹口服100 mg达沙替尼片,0~48 h间隔采集肘静脉血,分离血浆测定达沙替尼血药浓度,采用DAS 2.0软件计算药动学参数。结果：达沙替尼的主要药动学参数：C max为（204.2±60.6）ng·mL-1,T max为（0.55±0.13）h,t1/2为（5.5±1.4）h,AUC0~48 h为（668±207）ng·h·mL-1,AUC0~∞为（684±208）ng·h·mL-1,CL为（164.3±66.2）L·h-1,V为（1 341±1 022）L。结论：建立的LC-MS/MS测定法专属、灵敏,满足达沙替尼片药动学研究的要求。测得达沙替尼片在中国人体内的吸收明显高于美国人。

Objective： To establish an LC-MS /MS method for the determination of plasma concentration of dasatinib,and to study the pharmacokinetics of dasatinib tablets in healthy male Chinese volunteers.Methods： Twenty-four volunteers were given a single oral dose of 100 mg dasatinib tablets（Jiangsu Chia-tai Tianqing Pharmaceutical Co.Ltd.）.Venous blood samples were withdrawn at designed intervals between 0 and 48 h.The plasma concentrations of dasatinib were determined by the validated LC-MS / MS method and the pharmacokinetic parameters were calculated by DAS 2.0 software.Results： The main pharmacokinetic parameters after a single oral dose of 100 mg dasatinib tablets were as follows： C max was（204.2 ± 60.6） ng·mL-1,T max was（0.55 ± 0.13） h,t 1 /2 was（5.5 ±1.4） h,AUC 0 ~ 48 h was（668 ± 207） h·ng·mL-1,AUC 0 ~ ∞ was（684 ± 208） ng·h·mL-1,CL was（164.3 ±66.2） L·h-1and V was（1 341 ±1 022） L.Conclusion： The LC-MS/MS method has been proved to be specific and sensitive.The established method is successfully applied to the pharmacokinetics of dasatinib tablets in healthy male Chinese volunteers.The absorption in the Chinese volunteers is significantly higher than that of American volunteers.