尹咸淼 1宋欢 1夏睿 2丁峰 1姜敏生 1张艺 1郭东生 3甘方良3
作者信息
- 1. 湖北科技学院医学部药学院,湖北咸宁 437100||咸宁市中心医院临床药理机构办公室
- 2. 鄂州市中心医院药学部
- 3. 咸宁市中心医院临床药理机构办公室
- 折叠
摘要
Abstract
Objective To evaluate the bioequivalence and safety of the test and the reference formulation of Levodopa and Benseraz-ide Hydrochloride tablets in healthy Chinese subjects.Methods According to a two-sequence,four-period,completely replicated crossover design,76 healthy volunteers were divided into 40 fasting cases and 36 postprandial subjects.In each cycle,they were respectively adminis-tered the test formulation or the reference formulation of Madopar tablets.The plasma concentrations of levodopa and 2,3,4-trihydroxybenzyl-hydrazine were determined by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),and the pharmacokinetic parameters were calculated using pharmacokinetic software to evaluate the bioequivalence.Results Under fasting conditions,the Cmax of levo-dopa of the test formulation and the reference formulation were(4545.413±1992.017)and(4708.300±2341.716)ng/mL,respectively;the AUC0-t were(6531.0±1296.0)and(6571.6±1426.9)h·ng/mL,respectively;and the AUC0-∞ were(6581.6±1295.2)and(6616.1±1425.8)h·ng/mL,respectively.Under postprandial conditions,the Cmax of levodopa of the test formulation and the reference for-mulation were(3090.471±1565.144)and(2860.762±1300.407)ng/mL,respectively;the AUC0-t were(5565.3±1226.5)and(5530.8±1140.3)h·ng/mL,respectively;and the AUC0-∞ were(5621.3±1225.8)and(5585.8±1140.7)h·ng/mL,respectively.Under fasting conditions,the Cmax of 2,3,4-trihydroxybenzylhydrazine of the test formulation and the reference formulation were(54.341±14.709)and(56.965±17.084)ng/mL,respectively;the AUC0-t were(156.9±40.2)and(161.4±42.0)h·ng/mL,respectively;and the AUC0-∞ were(163.7±42.3)and(168.1±44.2)h·ng/mL,respectively.Under postprandial conditions,the Cmax of 2,3,4-trihydroxy-benzylhydrazine of the test formulation and the reference formulation were(45.748±10.160)and(44.722±9.959)ng/mL,respectively;the AUC0-t were(155.3±32.3)and(158.6±30.8)h·ng/mL,respectively;and the AUC0-∞ were(161.9±34.3)and(165.0±32.5)h·ng/mL,respectively.The 90％confidence intervals of the least squares geometric mean ratios of the pharmacokinetic parameters fell within the 80％～125％range.Conclusion The two formulations were bioequivalent under both fasting and postprandial conditions.No seri-ous adverse reactions occurred during the trial,and the safety was good.关键词
左旋多巴/2,3,4-三羟基苄基肼/生物等效性/药动学Key words
Levodopa/2,3,4-trihydroxybenzylhydrazine/Bioequivalence/Ph-armacokinetics分类
医药卫生
