磷酸二甲啡烷片在中国健康志愿者中的药物代谢动力学研究

目的研究磷酸二甲啡烷片在中国健康志愿者中单次和连续多次给药药动学特征。方法 12例受试者随机开放3×3拉丁方试验设计,研究单次给药和连续多次给药药动学特征。采用HPLC-MS/MS法测定血浆中二甲啡烷的药物浓度。药动学参数采用WinNonLin软件计算。结果单次口服(10、20、40 mg)磷酸二甲啡烷片后,二甲啡烷主要药动学参数:Cmax为(1.08±0.84)、(2.16±1.64)、(4.34±2.92)μg·L-1,tmax为(2.6±1.2)、(2.8±0.9)、(2.3±0.7)h,AUClast为(13.05±12.39)、(27.02±24.86)、(54.19±46.19)μg·h·L-1,AUCinf为(14.21±13.37)、(29.32±27.15)、(58.41±51.57)μg·h·L-1,t1/2为(9.23±3.56)、(10.94±2.73)、(11.21±2.51)h。多次给药20 mg后二甲啡烷主要药动学参数:Cmax为(5.22±4.28)μg·L-1,tmax为(2.5±1.3)h,AUClast为(75.82±74.39)μg·h·L-1,AUCinf为(82.37±82.21)μg·h·L-1,t1/2为(12.02±2.47)h。结论单次给药二甲啡烷的体内过程符合一级线性动力学过程;多次给药二甲啡烷的蓄积因子接近3,符合线性累加。

Pharmacokinetics of dimemorfan phosphate tablets in healthy Chinese volunteers

Objective To investigate the pharmacokinetics of dimemorfan phosphate tablets at single doses or multiple doses in healthy Chinese volunteers. Methods Single oral doses of dimemorfan phosphate tablets （10, 20, and 40 mg） were given to 12 healthy volunteers （half male and half female） according to an open, random 3 × 3 latin design and received multiple doses. The concentrations of dimemorfan in plasma were determined by high performance liquid chromatography/tandem mass spectrometry （HPLC-MS/MS） and the pharmacokinetic parameters were calculated using WinNonlin program. Results The main pharmacokinetic parameters of dimemorfan after single doses dimemorfan phosphate tablets （10, 20 and 40 mg） were as follows： CmaX was （1.08 ±0.84）, （2.16± 1.64） and （4.34±2.92） μg · L^-1, tmax was （2.6±1.2）, （2.8±0.9） and （2.3 ±0.7） h, AUClast was （13.05 v 12.39）, （27.02 ±24.86） and （54.19±46.19） μg ·h· L^-1, AUCinf was （14.21± 13.37）, （29.32±27.15） and （58.41 ±51.57） μg ·h· L^-1, t1/2 was （9.23±3.56）, （10.94±2.73） and （11.21 ±2.51） h. The parameters of dimemorfan after multiple doses （20 mg） were as follows： Cmax was （5.22±4.28） μg · L^-1, tmax was （2.5±1.3） h, AUClastWas （75.82±74.39） μg ·h· L^-1, AUCinfWas （82.37±82.21） μg ·h· L^-1, t1/2 was 02.02±2.47） h. Conclusion After 10 - 40 mg single doses ad- ministration, the pharmacokinetic results show that dimemorfan exhibits first order kinetic characteristics. After 20 mg multiple doses administration, the accumulation factor value is nearly 3 and dimemorfan shows a linear accumulation. Key words： dimemorfan; healthy volunteer; pharmacokinetics; HPLC-MS/MS