莫达非尼片的单、多剂量在健康志愿者体内药动学

目的建立莫达非尼血药浓度的高效液相色谱(HPLC)测定法,进行单、多剂量在人体的药动学研究。方法采用HPLC-UV法测定健康受试者口服莫达非尼片(单剂量含莫达非尼100,200,400 mg和多剂量)后血浆中莫达非尼浓度。结果单剂量口服莫达非尼(100,200和400 mg)后,估算的莫达非尼的药动学参数:t_(1/2β)分别为(15.7±s 1.0),(16.4±1.2),(15.6±1.3)h;CL分别为(2.2±0.3),(2.02±0.28),(2.2±0.4)L·h~(-1);t_(max)分别为(1.5±0.3),(1.7±0.3),(1.58±0.29)h;c_(max)分别为(3.0±0.5),(5.5±0.9),(11.4±1.5)mg·L~(-1);V_d分别为(56±20),(61±20),(57±11)L;AUC_(0～60)分别为(42.0±2.9),(74±6),(144±15)mg·h·L~(-1);AUC_(0～∞)分别为(50.4±2.4),(83±5),(154±15)mg·h·L~(-1);MRT_(0～60),兮别为(16.8±0.9),(17.4±1.0),(15.7±1.5)h。多剂量口服莫达非尼(100 mg,bid×7 d)血药浓度达稳态后估算的莫达非尼的药动学参数c_(max)~(ss)为(4.9±0.7)mg·L~(-1),t_(max)为(1.6±0.5)h,c_(min)~(ss)为(2.01±0.24)mg·L~(-1),c_(ax)为(3.2±0.4)mg·L~(-1),波动系数DF为(0.92±0.17),AUC_(0～12)~(ss)为(38±5)mg·h·L~(-1)。结论本方法准确、灵敏、可靠,莫达非尼在大部分人体内的过程符合二室开放模型,其主要药动学参数与国外文献报道数据一致,可为临床给药方案提供参考。

Study on pharmacokinetics of single and multi-dose of oral modafinil tablets in healthy volunteers

AIM To establish a HPLC-UV method for studying the pharmacokinetics of modafinil tablet with single and multo-dose in healthy volunteers.METHODS Healthy volunteers received tested tablets individually of a single oral dose containing modafinil 100,200,400 mg and muhidose.Drug concentrations in plasma were determined by HPLC-UV.RESULTS The main pharmacokinetic parameters of single oral doses (100,200,400 mg)were as follow:t_(1/2β)(15.7±s 1.0),(16.4±1.2),(15.6±1.3)h;CL(2.2±0.3), (2.02±0.28),(2.2±0.4)L·h~(-1);t_(max)(1.5±0.3),(1.7±0.3),(1.58±0.29) h;c_(max)(3.0±0.5),(5.5±0.9),(11.4±1.5)mg·L~(-1);V_d(56±20),(61±20),(57±11)L;AUC_(0-60)(42.0±2.9),(74±6),(144±15)mg·h·L~(-1);AUC_(0-∞)(50.4±2.4),(83±5),(154±15)mg·h·L~(-1);MRT_(0-60)(16.8±0.9),(17.4±1.0), (15.7±1.5)h.The main pharmacokinetic parameters of multidose(100 mg,bid×7 d)under stable concentratione were as follow:c_(max)~(ss)(4.9±0.7)mg·L~(-1),t_(max)(1.6±0.5)h,c_(min)~(ss)(2.01±0.24)mg·L~(-1),c_(av)(3.2±0.4)mg·L~(-1),DF(0.92±0.17),AUC_(0-12)~(ss)(38±5)mg·h·L~(-1).CONCLUSION The method is accurate, sensitive and reliable,coincided with a two-compartment open pharmacokinetic model for modafinil plasma concentration-time data analysis.The main pharmacokinetic parameters of the domestic modafinil tablet were similar to those reported abroad,providing information for clinical application.