国产格列本脲和二甲双胍复方制剂在健康志愿者的药代动力学和生物等效性

Pharmacokinetics and bioequivalance of domestic compound glibenclamide and metformin in chinese healthy volunteers

目的 研究国产复方格列本脲和盐酸二甲双胍胶囊单剂量人体的药代动力学特性和生物等效性。方法 以国产格列本脲片和进口盐酸二甲双胍片为标准参比制剂,入选的20名受试者随机交叉口服单剂量试验与参比制剂,用液相色谱-质谱法测定血浆中格列本脲和二甲双胍的浓度。结果 格列本脲的药代动力学参数分别为:AUC0-t为(603.32±196.61)和(581.70±195.01) ng.h.mL-1,Cmax为(123.46±27.03)和(128.28±3.67) ng.mL-1,tmax为(2.8±0.7)和(2.6±0.6 ) h,t1/2为(6.54±1.24)和(6.89±1.73) h。二甲双胍药代动力学参数分别为:AUC0-t为(7832.97±2603.38)和(7765.52±2870.85) ng. h.mL-1,Cmax为(1377.55±476.60)和(1367.40±551.19 )ng.mL-1,tmax为(2.7±0.9)和(2.0±0.5 ) h,t1/2为(5.72±1.24)和(5.81±1.51) h。试验制剂中格列本脲的相对生物利用度为(104.82±19.27)%,二甲双胍的相对生物利用度为(107.30±46.40)%。结论 试验制剂与参比制剂具有生物等效性。

Objective To evaluate the pharmacokinetic parameters of a new domesticcompound glibenclamide and metformin and its relative bioavailability in healthyvolunteers. Methods A randomized, open, crossover study of 20 healthy Chinesevolunteers was conducted with a oral single dose of capsule (glibenclamide 1.25mg and metformin 250 mg per pill) 2 pills or glibenclamide 2.5 mg and metformin 500mg were given at the same time. The plasma concentrations of glibenclamide andmetformin in healthy volunteers were determined by an validated LC-MS/MS methodand were assessed with non-compartment model to obtain the pharmacokineticparameters. The relative bioavailability of compound glibenclamide and metformincapsule versus glibenclamide and metformin were calculated. Results Thepharmacokinetic parameters of glibenclamide for orally administered domesticglibenclamide capsule and glibenclamide and metformin were as following: AUC0-t :(603.32±196.61) and (581.70±195.01) ng.h.mL-1;Cmax :(123.46±27.03)and (128.28±3.67) ng.mL-1;tmax: (2.8±0.7) and (2.6±0.6) h; t1/2:(6.54±1.24)and (6.89±1.73) h. The pharmacokinetic parameters of metformin for orallyadministered domestic glibenclamide capsule and glibenclamide and metforminwere as following: AUC0-t : (7832.97±2603.38) and (7765.52±2870.85) ng. h.mL-1;Cmax: (1377.55±476.60) and (1367.40±551.19)ng.mL-1; tmax; (2.7±0.9) and (2.0±0.5) h; t1/2: (5.72±1.24) and (5.81±1.51)h, respectively. There were no significant differences(P>0.05) in AUC0-t , tmax, Cmax and t1/2 between two preparations.The relative bioavailability of glibenclamide and metformin of glibenclamide casule were (104.82±19.27)% and (107.30±46.40)% compared with glibenclamide and metformin tablets. No clear adverse events were observed during this study.Conclusion glibenclamide capsule and glibenclamide and metformin tablets were bioequivalent.