摘要
目的评价2种布洛芬片在中国健康受试者中的生物等效性,为一致性评价和临床使用提供依据。方法采用单次给药、随机、开放、两周期、双交叉设计,空腹、餐后各42例健康受试者,分别随机分为2组,单次口服布洛芬片受试制剂和参比制剂各0.2 g,用液相色谱-串联质谱法(LC-MS/MS)检测人血浆中布洛芬的浓度,用Phoenix WinNonlin软件(8.0版本),以非房室模型计算药代动力学参数,并评价两种制剂的生物等效性;在试验期间对受试者进行相关的安全性评价。结果单剂量空腹给药后布洛芬主要药代动力学参数如下。受试制剂和参比制剂的Cmax分别为(1.76×10^4±3218.46)和(1.94×10^4±4513.33)ng·mL^-1,AUC0-t分别为(6.69×10^4±1.17×10^4)和(6.45×10^4±1.34×10^4)h·ng·mL^-1,AUC0-∞分别为(6.88×10^4±1.23×10^4)和(6.69×10^4±1.33×10^4) h·ng·mL^-1。受试制剂和参比制剂的Cmax、AUC0-t和AUC0-∞的几何均值比的90%置信区间分别为85.13%~100.62%,100.11%~109.88%和99.64%~107.56%。单剂量餐后给药后布洛芬主要药代动力学参数如下。受试制剂和参比制剂的Cmax分别为(1.61×10^4±4083.11)和(1.62×10^4±4688.51)ng·mL^-1,AUC0-t分别为(5.97×10^4±1.09×10^4)和(6.02×10^4±1.29×10^4)h·ng·mL^-1,AUC0-∞分别为(6.26×10^4±1.33×10^4)和(6.32×10^4±1.48×10^4)h·ng·mL^-1。受试制剂和参比制剂的Cmax、AUC0-t和AUC0-∞的几何均值比的90%置信区间分别为93.08%~109.35%,97.16%~102.40%和96.78%~102.22%,均在80%~125%,判断两种制剂具有生物等效性。此外,在试验期间所有受试者所发生的不良事件均为轻度呈一过性,未发生严重不良事件。结论布洛芬片受试制剂和参比制剂具有生物等效性,安全性良好。
Objective To evaluate the bioequivalence of two kinds of ibuprofen tablets in healthy Chinese subjects after single oral administration to provide a basis for consistency evaluation and clinical use. Methods Using a single-dose, randomized, open-lable, two-period, two-way crossover design, 42 healthy subjects for fasting study and 42 healthy subjects for fed study were enrolled, respectively, and randomized into two groups to receive a single dose of test(T) 0.2 g or reference(R) 0.2 g with 7-day washout period. Plasma concentration of ibuprofen was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS) method. The pharmacokinetic parameters were calculated by Win Nonlin software(8. 0 version) using non-compartmental model, and bioequivalence evaluation was performed for the two preparations. Relevant safety evaluations were performed during the trial. Results The main pharmacokinetic parameters of ibuprofen after a single oral dose of ibuprofen tablet under fasting condition for T and R were as follows: Cmaxwere(1. 76 ×10^4± 3218. 46) and(1. 94 ×10^4± 4513. 33)ng·mL^-1;AUC0-twere(6. 69 ×10^4± 1. 17 ×10^4) and(6. 45 ×10^4± 1. 34 ×10^4) h·ng·mL^-1,and AUC0-∞ were(6. 88 ×10^4± 1. 23 ×10^4) and(6. 69 ×10^4± 1. 33 ×10^4) h·ng·mL^-1,respectively. The 90% CIs for the geometric mean ratios(GMR) of Cmax,AUC0-t and AUC0-∞ of T and R under fasting condition were 85. 13%-100. 62%,100. 11%-109. 88% and 99. 64%-107. 56%,respectively. The main pharmacokinetic parameters of Ibuprofen under fed condition for T and R were as follows: C4 maxwere(1. 61 × 10± 4083. 11) and(1. 62 ×10^4±4688. 51) ng·mL^-1,AUC0-t were(5. 97 ×10^4± 1. 09 ×10^4) and(6. 02 ×10^4± 1. 29 ×10^4) h·ng·mL^-1,and AUC0-∞were(6. 26 ×10^4± 1. 33 ×10^4) and(6. 32 ×10^4± 1. 48 ×10^4) h·ng·mL^-1. The 90% CIs for GMR of Cmax,AUC0-t and AUC0-∞of T and R under fed condition were 93. 08%-109. 35%,97. 16%-102. 40% and 96. 78%-102. 22%,respectively. The results demonstrated the bioequivalence of the ibuprofen tablets between T and R. All adverse events occurred were mild and transient,and no serious adverse event was reported. Conclusion The test formulation and reference formulation of ibuprofen tablets were equivalent and safe.
作者
李晓斌
喻明
汪楠
吴秀君
马然
郑忠辉
潘西海
高雪
王文萍
LI Xiao-bin;YU Ming;WANG Nan;WU Xiu-jun;MA Ran;ZHENG Zhong-hui;PAN Xi-hai;GAO Xue;WANG Wen-ping(PhaseⅠClinical Trial Ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Shandong Xinhua Pharmaceuticals Co.,Ltd.,Zibo 255086,Shandong Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第22期3600-3604,共5页
The Chinese Journal of Clinical Pharmacology
基金
辽宁中医药大学中药临床药理学科建设基金资助项目(辽中医校发2016-198)
辽宁省”兴辽英才计划”基金资助项目(XLYC1802008)
辽宁省中药临床药物代谢动力学重点实验室基金资助项目(辽科发2005-16)
国家重点研发计划项目基金资助项目(2018YFC1311600)
辽宁省自然科学基金资助项目(20170520022)。