空腹口服国产氨酚双氢可待因制剂的生物等效性初步评价研究

Preliminary Evaluation of Bioequivalence of Domestic Aminophenol Dihydrocodeine Tablets with Empty Stomach

目的:初步评价氨酚双氢可待因片在健康志愿者体内的生物等效性。方法:采用随机交叉对照设计,10名健康受试者分别于空腹条件下单剂量口服氨酚双氢可待因片之受试制剂与参比制剂,并于服药后14h内多点抽取静脉血,LC-MS/MS法测定血浆样本中对乙酰氨基酚与酒石酸双氢可待因的血药浓度,采用Phoenix WinNonlin软件计算主要药动学参数并进行生物等效性评价。结果:单剂量口服受试制剂与参比制剂后,血浆中对乙酰氨基酚的C_(max)分别为(9.36±3.33),(8.18±1.43) ug/mL;AUC_(0-t)分别为(1920.05±480.02),(1892.79±400.30) ug/mL·min;AUC_(0-∞)分别为(2058.16±486.43),(2033.10±400.64) ug/mL·min。双氢可待因的C_(max)分别为(47.16±11.33),(44.99±7.34) ng/mL;AUC_(0-t)分别为(12858.47±3512.03),(13229.29±3115.98) ng/mL·min;AUC_(0-∞)分别为(14278.28±4149.34),(14884.58±3503.93) ng/mL·min。结论:10例中国健康受试者空腹服用国产与原研药物氨酚双氢可待因片生物不等效,若要达到生物等效结论,推算需将受试者例数放大至20例。可依此方案进一步扩大样本量开展正式试验。

Objective:To preliminary evaluate the bioequivalence of aminophenol dihydrocodeine tablets in healthy volunteers.Methods:A randomized cross-control design was used,with 10 healthy subjects with empty stomach were given a single dose of oral aminophenol dihydrocodeine tablets as a test preparation and as a reference preparation respectively,venous blood was collected at multiple points within 14h after administration;Blood concentrations of acetaminophen and dihydrocodeine tartrate in plasma samples were determined by LC-MS/MS assay;Phoenix WinNonlin software was used to calculate the main pharmacokinetic parameters and evaluate the bioequivalence.Results:After the single dose of oral test preparation(T) and reference preparation(R),the Cmax of acetaminophen in plasma were (9.36±3.33) and (8.18±1.43)ug/mL respectively,AUC0-t were (1920.05±480.02)and (1892.79±400.30)ug/mL·min respectively,AUC0-∞ were (2058.16±486.43)and(2033.10±400.64)ug/m·min respectively.Conclusion:Under the condition of empty stomach,the domestic aminophenol dihydrocodeine tablets test preparation was not bioequivalent to the imported aminophenol dihydrocodeine tablets in 10 subjects;To reach the bioequivalent conclusion,the number of subjects needs to be enlarged to 20 subjects.According to this scheme,the sample size can be further expanded to carry out formal tests.