2种消旋卡多曲制剂的人体生物等效性研究

Study on the Bioequivalence of 2 Kinds of Racecadotril Preparations in Healthy Volunteers

目的:研究消旋卡多曲散剂与消旋卡多曲颗粒的生物等效性。方法:20名健康男性志愿者随机交叉单剂量口服消旋卡多曲散剂(受试制剂)或消旋卡多曲颗粒(参比制剂)200mg后,采用液-质联用法测定血药浓度,以DAS2.0软件计算药动学参数,并评价其生物等效性。结果:受试者单剂量口服200mg消旋卡多曲受试制剂或参比制剂后,药动学参数分别为:cmax(286.54±66.14)、(283.73±65.49)ng·mL-1,tmax(1.78±0.48)、(1.68±0.79)h,t1/2(4.02±1.26)、(4.00±1.11)h,AUC0～24h(1353±431)、(1293±320)ng·h·mL-1。经方差分析、双单侧t检验及1-2α置信区间法统计分析,各药动学参数差异无统计学意义(P>0.05)。受试制剂中消旋卡多曲的cmax、AUC0～24h、AUC0～∞的90%置信区间分别为92.2%～111.1%、98.1%～107.7%、98.6%～108.3%。结论:消旋卡多曲散剂与消旋卡多曲颗粒在人体内生物等效。

OBJECTIVE：To study the bioequivalence of Racecadotril pulvis and Racecadotril granules.METHODS：A randomized crossover design was performed in 20 healthy male volunteers.A single oral dose of Racecadotril pulvis（200 mg,test preparation） or Racecadotril granules（200 mg,reference preparation） were administrated.Plasma concentrations of racecadotril were determined by LC-MS.The pharmacokinetic parameters were calculated by DAS 2.0 software and the bioequivalence was evaluated.RESULTS：After a single oral dose of 200 mg test preparation or reference preparation,the main pharmacokinetic parameters were as follows：cmax（286.54±66.14）ng·mL-1 and（283.73±65.49）ng·mL-1;tmax（1.78±0.48）h and（1.68±0.79） h;t1/2（4.02±1.26） h and（4.00±1.11） h;AUC0～24 h（1 353±431） ng·h·mL-1 and（1 293±320）ng·h·mL-1.There was no significant difference between the two preparations in pharmacokinetic parameters by variance analysis,t test and 1-2α confidence interval method（P0.05）.The 90% confidence intervals of cmax,AUC0～24 h and AUC0～∞of test preparation were 92.2%～111.1%,98.1%～107.7% and 98.6%～108.3%.CONCLUSION：Racecadotril pulvis and Racecadotril granules are bioequivalent in healthy volunteers.