单次静脉输注极低剂量注射用替莫唑胺在中国男性健康受试者中的0期临床研究

Phase 0 clinical trial of single-microdose intravenous temozolomide in healthy Chinese male volunteers

目的评价单次静脉点滴极低剂量注射用替莫唑胺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 14名中国健康男性受试者,给予静脉点滴2 mg·m^(-2)注射用替莫唑胺,用高效液相色谱-串联质谱联用(LC-MS/MS)方法测定给药后不同时间替莫唑胺的血药浓度,并Win Nolin 6.1软件计算主要药代动力学参数。结果本研究未观察到不良事件和严重不良事件。单次静脉点滴2 mg·m^(-2)注射用替莫唑胺后的药代动力学参数如下:Cmax为(141.00±27.10)ng·m L^(-1),tmax为(1.34±0.21)h,t1/2为(1.90±0.10)h,AUC0-24 h为(430.00±78.70)ng·m L^(-1)·h,AUC0-∞为(437.00±79.80)ng·m L^(-1)·h,清除率为(4.79±1.29)L·h-1,表观分布容积为(13.10±3.76)L。结论注射用替莫唑胺0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0期微剂量研究无任何临床和实验室不良事件发生。

Objective To evaluate the pharmacokinetics and safety of single microdose intravenous temozolomide in healthy Chinese volunteers. Methods Fourteen subjects were randomly assigned to take a single microdose of 2 mg m-2 intravenous temozolomide. The serum concen- trations of temozolomide were assayed with liquid chromatography - tan- dem mass spectrometry （LC -MS/MS）. Results No adverse events and serious adverse events were detected. The following pharmacokinetic parameters detected after a single microdose of 2 nag m-2 intravenous temozolomide were calculated by WinNolin 6. 1 software ： CmaX （141.00±27. 10）ng mL-1, tmax（1.34 ±0.21）h, t1/2（1.90 ±0. 10） h, AUC0-24h （430.00 ± 78.70 ） ng mL-1 h, AUC0- （437.00±79.80）ng h mL-1,clearance （4.79±1.29）L h-1, aparent volume of distribution （ 13.10 ± 3.76 ） L. Conclusion Phar- maeokinetic parameters of phase 0 research of intravenous temozolomide reflected the characteristics of the drug distribution and elimination in some extent, thus it was with clinical significance to protect subjects in phase 0 research by taking mierodose intravenous temozolomide.