莫达非尼片在健康人体的药代动力学研究

Pharmacokinetic Study of Modafinil Tablets in Healthy Volunteers

目的在中国健康男性志愿者中进行莫达非尼片的药动学研究。方法30名男性健康志愿者随机分为3个剂量组:单次口服给药低、中、高剂量(100,200,400 mg)组;多次口服给药组,每天给药1次,每次200 mg,连续给药7 d。采用高效液相色谱法(HPLC)测定血浆中莫达非尼浓度。应用DAS2.0软件进行数据处理,求算药动学参数。结果莫达非尼片单次口服给药低、中、高剂量组主要药动学参数AUC0-t分别为(33.49±9.31),(82.52±20.88),(173.72±38.60)mg·h/L;AUC0-∞分别为(36.05±10.51),(87.70±24.42),(189.33±53.81)mg·h/L;Cmax分别为(2.44±0.35),(5.45±0.93),(9.90±1.13)mg/L;tmax分别为(2.35±0.85),(2.35±1.00),(2.70±0.89)h;t1/2分别为(14.08±3.31),(14.52±2.48),(15.99±3.59)h;多次口服给药组主要药动学参数分别为:AUCss为(88.60±28.84)mg·h/L;AUC0-t为(124.80±48.71)mg·h/L;AUC0-∞为(136.53±60.80)mg·h/L;Css_max为(6.99±1.68)mg/L;Css_min为(1.98±1.02)mg/L;tmax为(1.95±0.96)h;t1/2为(16.26±3.03)h。单次口服给药3个剂量药动学参数AUC0-∞,Cmax,t1/2z,CLz,Vz经方差分析后组间差异无统计意义(P>0.05);多次口服给药达稳态时的AUC0-t,AUC0-∞与单次给药相比有所升高,差异具有统计学意义(P<0.05)。结论单次口服莫达非尼片在中国健康男性受试者体内的代谢规律符合线性药动学特征。

Objective To study the pharmacokinetic profile of Modafinil Tablets in Chinese healthy male volunteers.Methods 30 healthy male volunteers were divided randomly into low,medium and high dose groups,in which the volunteers received a single dose of 100,200 or 400 mg of Modafinil Tablets orally,respectively.The volunteers who received 200 mg of Modafinil Tablets once then received Modafinil Tablets for 7 consecutive days,200 mg once daily.The plasma concentration of Modafinil was determined by HPLC,and the pharmacokinetic parameters were calculated by DAS 2.0 software.Results The main pharmacokinetic parameters of a single oral dose of 100,200 and 400 mg of Modafinil Tablets were as follows:AUC0-t:(33.49±9.31),(82.52±20.88),(173.72±38.60)mg·h/L;AUC0-∞:(36.05±10.51),(87.70±24.42),(189.33±53.81)mg·h/L;Cmax:(2.44±0.35),(5.45±0.93),(9.90±1.13)mg/L;tmax:(2.35±0.85),(2.35±1.00),(2.70±0.89)h;t1/2:(14.08±3.31),(14.52±2.48),(15.99±3.59)h.The main pharmacokinetic parameters of multiple oral doses of Modafinil Tablets were as follows:AUCss:(88.60±28.84)mg·h/L;AUC0-t:(124.80±48.71)mg·h/L;AUC0-∞:(136.53±60.80)mg·h/L;Css_max:(6.99±1.68)mg/L;Css_min:(1.98±1.02)mg/L;tmax:(1.95±0.96)h;t1/2:(16.26±3.03)h.There were no significant difference between AUC0-∞,Cmax,t1/2z,CLz,Vz of different single dose of Modafinil Tablets(P>0.05).AUC0-t and AUC0-∞increased after repeated administration(P<0.05).Conclusion The metabolism of Modafinil in Chinese healthy male subjects is in line with the linear pharmacokinetic characteristics.