布洛芬颗粒在中国健康受试者体内的人体生物等效性研究

A Bioequivalence Study on Ibuprofen Granules in Chinese Healthy Subjects

目的研究布洛芬颗粒剂在中国健康受试者体内的生物等效性,为一致性评价提供依据。方法采用单中心、随机、开放、单剂量、两周期、两序列、交叉试验设计,将纳入的空腹、餐后各24名健康志愿者分别随机分为2组,分别口服受试制剂和参比制剂0.2 g,采用超高效液相色谱串联质谱(UPLC-MS/MS)技术,建立了快速、简单、灵敏的测定人血浆中布洛芬浓度的分析方法,用于布洛芬颗粒人体生物等效性试验研究。采用Phoenix WinNonlin 8.2软件计算其药动学参数,评价其生物等效性。结果空腹给药后布洛芬受试制剂和参比制剂的主要药动学参数为:C_(max)分别为(21.8±4.21)μg/ml和(23.3±4.74)μg/ml;T_(max)分别为1.00 h和0.25 h;AUC_(0-t)分别为(71.83±16.08)μg/ml和(69.02±16.34)μg/ml;AUC_(0-∞)分别为(72.89±16.27)μg/ml和(70.04±16.53)μg/ml。餐后给药后布洛芬受试制剂和参比制剂的主要药动学参数为:C_(max)分别为(10.7±2.25)μg/ml和(10.6±2.57)μg/ml;T_(max)分别为4.00 h和4.00 h;AUC_(0-t)分别为(65.27±13.79)μg/ml和(65.76±16.37)μg/ml;AUC_(0-∞)分别为(66.45±14.13)μg/ml和(67.12±16.93)μg/ml。结论空腹和餐后受试制剂AUC_(0-t)、AUC_(0-∞)和C_(max)的90%置信区间均在参比制剂相应参数的80.00%~125.00%范围内。方差分析及双单侧t检验结果显示,受试制剂布洛芬颗粒剂与参比布洛芬颗粒剂具有生物等效性。

Objective To study the bioequivalence of Ibuprofen Granules in Chinese healthy subjects to provide a basis for consistency evaluation.Methods An single-center,randomized,open,single-dose,two-period,two-sequence and crossover design was adopted.24 healthy subjects for fasting study and 24 healthy subjects for fed study were enrolled,respectively,and randomized into two groups to receive a single dose of test preparation(0.2 g)or reference preparation(0.2 g).A rapid,simple and sensitive UPLC-MS/MS method was developed for determination of ibuprofen in human plasma which was used in the preliminary study of bioequivalence of Ibuprofen Granules in human body.The pharmacokinetic parameters were calculated and the bioequivalence was evaluated by Phoenix WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test preparation and the reference preparation under fasting condition were as follows:C_(max) were(21.8±4.21)μg/ml and(23.3±4.74)μg/ml;T_(max) were 1.00 h and 0.25 h;AUC_(0-t) were(71.83±16.08)μg/ml and(69.02±16.34)μg/ml;AUC_(0-∞)were(72.89±16.27)μg/ml and(70.04±16.53)μg/ml,respectively.The main pharmacokinetic parameters of the test preparation and the reference preparation under fed condition were as follows:C_(max) were(10.7±2.25)μg/ml and(10.6±2.57)μg/ml;T_(max) were 4.00 h and 4.00 h;AUC_(0-t) were(65.27±13.79)μg/ml and(65.76±16.37)μg/ml;AUC_(0-∞)were(66.45±14.13)μg/ml and(67.12±16.93)μg/ml,respectively.Conclusion The 90%confidence intervals of AUC_(0-t),AUC_(0-∞)and C_(max) of the test preparation were within the ranges of 80.0%-125.0%of the corresponding parameters of the reference preparation.The results of ANOVAR and two one-side t-tests show that the test preparation and reference preparation are bioequivalent.