单次口服极低剂量甲磺酸伊马替尼在中国男性健康受试者的零期临床研究

Phase 0 clinical trial of single-dose imatinib mesylate in health Chinese male volunteers

目的评价单次口服极低剂量甲磺酸伊马替尼在中国男性健康受试者体内的药代动力学特征及安全性。方法 8名中国健康男性受试者给予单次口服甲磺酸伊马替尼胶囊4 mg,用LC-MS/MS法测定给药后不同时间甲磺酸伊马替尼的血药浓度并计算主要药代动力学参数。结果受试者给予单次口服甲磺酸伊马替尼胶囊4 mg后的主要药代动力学参数:Cmax(12.70±6.61)ng·m L-1,tmax(1.94±0.94)h,AUC0-24 h(90.10±37.70)ng·m L-1·h,t1/2(10.40±5.01)h,CL/F(47.20±33.40)L·h-1,V/F(541.00±128.00)L,MRT(7.21±1.30)h。本研究未观察到不良事件和严重不良事件。结论伊马替尼零期微剂量研究药代动力学参数能够在一定程度上反映药物的分布和消除特点,且零期微剂量研究无任何临床和实验室不良事件发生,从保护受试者的角度具有特别的意义。

Objective To evaluated the pharmacokinetics and safety of single microdose imatinib mesylate in Chinese health volunteers. Methods Eight subjects were randomly assigned to take orally a single microdose of 4 mg imatinib mesylate. The serum concentrations of imatinib were assayed with LC - MS/MS. Results The following pharmacokinetic parameters were calculated by WinNolin 6. 3 software. Cmax （12.70 ±6.61 ） ng· mL^-1, tmax （1.94 ±0.94） h, AUC0-24h （90.10±37.70）ng·mL^- 1 .h, t1/2 （10.40 ±5.01 ） h, CL/F （47.20±33.40）L·h^-1, V/F （ 541.00 ±128;00 ） L, MRT （7.21 ±1.30）h. No adverse events and serious adverse events were detected. Conclusion Pharm-acokinetic parameters of phase 0 research of imatinib mesylate reflected the characteristics of the drug distribution and elimination in some extent. It was significant to protect subjects in phase 0 research by taking microdose imatinib mesylate.