普瑞巴林胶囊的人体药动学研究

 目的在12名健康志愿者体内研究普瑞巴林胶囊的药动学特征,为该药进行临床研究及合理应用提供依据。方法12名健康志愿者,男女各半,采用3×3拉丁方给药方案,分别于不同周期单次给药口服试验制剂75,150和300mg,并于单次给药试验结束后,按照每天早、晚各服药一次,每次75mg,连续服用5d的给药方案进行多次给药研究。应用HPLC-UV测定服药后不同时间点普瑞巴林的血药浓度。结果模型拟合结果显示,普瑞巴林进入人体后的药物经时过程符合血管外给药二室模型。单次服用75,150和300mg普瑞巴林胶囊后,其主要药动学参数如下:ρ_max为(2.43±0.36),(4.59±0.91)和(9.16±1.00)mg·L^-1;AUC_0-t为(13.5±2.6),(27.4±6.2)和(54.9±10.3)mg·h·L^-1;t_max为(0.96±0.42),(0.90±0.39)和(1.21±0.38)h;t_1/2β为(6.6±2.3),(7.2±2.8)和(5.8±1.4)h。连续口服5d75mg,bid普瑞巴林胶囊后,其药动学参数分别为:ρ_max为(2.83±0.42)mg·L^-1,ρ_min为(0.67±0.14)mg·L^-1,ρ_av为(1.18±0.20)mg·L^-1,AUC_0-t为(19.4±3.8)mg·h·L^-1,t_max为(0.79±0.30)h,t_1/2β为(6.8±2.6)h,DF为(1.86±0.39)。对单次给药试验中所得的AUC,ρ_max,t_1/2与剂量进行线性相关性分析,结果表明,AUC和ρ_max与剂量呈线性相关,t_1/2β与剂量无关,符合1级速率过程,对其他药动学参数进行剂量间、个体间、周期间及性别间方差分析显示,各组间均无显著性差别。结论普瑞巴林胶囊单次给药剂量在75～300mg内,体内过程符合1级速率过程。按照75mg,bid的方案连续服用普瑞巴林5d,药物在体内无蓄积。

Pharmacokinetics of Pregabalin Sulfate in Human

OBJECTIVE To study the pharmacokinetics of pregabalin sulfate capsules in twelve healthy volunteers.METHODS A single oral dose of 75,150 and 300 mg pregabalin sulfate were given to 12 healthy volunteers(6 male and 6 female) in a cross-over-design.The multiple dose studies were done after the single dose studies,and the dosage regimen was 75 mg bid for 5 d.The plasma concentrations of pregabalin were determined by HPLC-UV method.RESULTS The pharmacokinetics pregabalin was described by two compartment model.The main pharmacokinetic parameters of pregabalin were as follows:ρ_max(2.43 ± 0.36),(4.59 ± 0.91) and(9.16 ± 1.00)mg·L^-1;AUC_{0-t(13.5±2.6),(27.4±6.2) and(54.9±10.3) mg·h·L^-1;tmax(0.96±0.42),(0.90 ± 0.39) and(1.21 ± 0.38)h;t1/2β(6.6 ± 2.3),(7.2 ± 2.8) and(5.8 ± 1.4)h,respectively in single dose studies,ρmax(2.83 ± 0.42) mg·L^-1,ρmin(0.67 ± 0.14) mg·L^-1,ρav(1.18 ± 0.20)mg·L^-1,AUC0-t(19.4 ± 3.8)mg·h·L^-1,tmax(0.79 ± 0.30) h,t1/2β(6.8 ± 2.6)h,DF(1.86 ± 0.39),in multiple dose studies.In single dose studies,the ρmax and AUC showed the c dose-response relationship.There were no significant differences in the subjects and genders.CONCLUSION:Pregabalin was described by linear pharmacokinetic procedure in the single dose regimens from 75 to 300 mg.The pharmacokinetic parameters of multiple dose regimen were not significantly different from that of single dose regimen at the same dose.}