莫达芬尼酸在人体血浆中药动学研究

The pharmacokinetics sdudy of Modafinil acid in plasma of healthy volunteers

目的 :观察中国健康成年志愿者单次口服莫达芬尼片剂后 ,其代谢产物莫达芬尼酸血浆浓度 ,为Ⅱ期临床试验提供试验参数。方法 :9名受试者按拉丁方设计随机分组 ,分别依次单次口服 10 0mg、2 0 0mg、30 0mg 3个剂量的莫达芬尼片后 ,应用高效液相色谱法 (HPLC)测定各受试者血浆莫达芬尼酸浓度 ,采用 3P97软件计算药代动力学参数。结果 :10 0mg、2 0 0mg、30 0mg组莫达芬尼酸主要药代动力学参数分别为 :Cmax(1.78± 0 .79)mg·L 1、(3.17± 1.2 7)mg·L 1、(4 .13± 2 .32 )mg·L 1;Tmax1.8h、3.1h、2 .8h ;t1/2 β (2 .35± 1.97)h、(2 .4 5± 1.0 7)h、(1.95± 1.18)h ;AUC0 t(2 1.17± 16 .13)mg·h·L 1、(2 5 .74± 7.74 )mg·h·L 1、(4 1.38± 2 0 .72 )mg·h·L 1;CL (5 .79± 5 .19)L·h$C1、(7.80±3.4 2 )L·h$C 1、(7.95± 2 .97)L·h$C1;结论 :莫达芬尼酸药 时曲线符合二房室模型 ,高、中、低三个剂量的Cmax、AUC0 t随给药剂量加大而增加 ;t1/2 β、Tmax。

Objective:Modafinil acid concentrations of its metabolite in plasma was determined following a single oral dose of modafinil tablet in Chinese heathy volunters to prove the pharmacokinetic parameters in modafinil clinical trials.Methods:After 9 volunteers were taken respectively single-dose of 100mg, 200mg, 300mg modafinil tablet randomly by Latin method with 3 subjects in eath group,modafinil acid concentrations in plasma by HPLC method. The pharmacokinetic parameters were calculated by using 3P97program. Results:The main pharmacokinetic parameters of modafinil acid in 100mg、200mg、300mg groug were: Cmax 1.78±0.79mg·L -1、3.17±1.27mg·L -1 and 4.13±2.0.3mg·L -1,T max 1.8h、3.1h and 2.8h,t 1/2β 2.35±1.97h、 2.45±1.07h and 1.95±1.18h,AUC 0-t 21.17±16.13mg·h·L -1、25.74±7.74mg·h·L -1 and 41.38±20.72mg·h·L -1,CL 5.799±5.190 L·h –1、7.800±3.420 L·h –1 and 7.954±2.976 L·h –1,modafinil tablet respectively.Conclusion:Cmax、AUC 0-tof modafinil acid was increased on the dosage of modafinil.There are no statistically singnificant between t 1/2β、T max、CL and dosage of modafinil.