健康受试者口服酒石酸罗格列酮片的药动学与生物等效性研究

Bioequivalence of rosiglitazone tartrate tables and rosiglitazone maleate tables in healthy volunteers

目的:研究健康中国男性受试者单剂量服用4 mg酒石酸罗格列酮片的药动学特征。方法:采用单中心、随机研究,健康男性志愿者随机交叉空腹单次口服4 mg酒石酸罗格列酮片及马来酸罗格列酮片,分别于服药前及服药后0.17,0.33,0.5,1.0,1.5,2,4,6,8,12,16,24 h采集血样,用LC-MS/MS法测定血浆中罗格列酮的浓度,并对试验数据进行统计处理。结果:空腹单次口服4 mg酒石酸罗格列酮片和马来酸罗格列酮片药动学参数分别为Tmax为(0.61±0.29)和(0.72±0.37)h,Cmax为(487±134)和(487±156)n.gmL-1,t1/2为(4.33±1.00)和(4.43±0.98)h;AUC0-t为(2 256±822)和(2 261±902)μg.h.mL-1,AUC0∞-为(2 309±870)和(2 318±951)μg.h.mL-1。酒石酸罗格列酮片的相对生物利用度平均为(102.3±17.5)%。结论:主要药动学参数符合二室药动学模型,酒石酸罗格列酮片和对照马来酸罗格列酮片具有生物等效性。

Objective：To evaluate the relative bioavailability and bioequivalence of rosiglitazone tartrate tables and rosiglitazone maleate tables in healthy volunteers.Methods： Single oral doses（4 mg） of rosiglitazone tartrate tables and rosiglitazone maleate tables were respectively administered to 20 healthy male volunteers in randomized crossover study.LC-MS/MS assay was applied to determine the concentration of rosiglitazone in serum.Results： The pharmacokinetic parameters after single oral doses of 4 mg rosiglitazone tartrate tables and rosiglitazone maleate tables were as follows： Tmax（0.61±0.29） and（0.72±0.37）h;Cmax（487±134） and（487±156） μg·mL-1;t1/2（4.33±1.00） and（4.43±0.98） h;AUC0-t（2 256±822） and（2 261±902） μg·h·mL-1;AUC0-∞（2 309±870） and（2 318±951） μg·h·mL-1.There were no significant differences between the parameters of 2 tablets.Conclusion： The concentration-time curve of rosiglitazone fitted to a two-compartment pharmacokinetic model.The relative bioavailability of single oral administration is（102.3±17.5）%.The two preparations are of bioequivalence.