消旋卡多曲口腔崩解片相对生物利用度研究

Relative bioavailability of racecadotril orally disintegrating tablets in healthy volunteers

目的:以进口消旋卡多曲胶囊为参比制剂,比较国产消旋卡多曲口腔崩解片的人体相对生物利用度和等效性。方法:20例健康男性志愿者随机自身交叉对照试验设计,受试者分别单剂口服受试制剂198 mg和参比制剂200 mg后,用柱切换HPLC内标法测定消旋卡多曲活性代谢物(Thiophine,TP)浓度,DAS ver 1．0程序计算药动学参数并进行生物等效性分析。结果:受试制剂与参比制剂的AUC0-11h分别为(1 267±494)和(1 138±415)μg·h·L-1,Cmax分别为(886±334)和(744±339)μg·L-1,Tmax分别为(1．24±0．84)和(1．15±0．79)h。受试制剂的AUC0-11h和Cmax[1～2α]置信区间分别为102．3％～120．1％和101．7％～145．4％,Tmax经非参数法检验差异无统计意义,其相对生物利用度为(114．6±24．5)％。结论:两制剂生物等效,但卡多曲口腔崩解片峰浓度较参比制剂略高。

Objective：To investigate bioavailability of domestic racecadotril orally disintegrating tablets （test） versus imported racecadotril capsules （reference）. Methods：20 healthy male volunteers were randomized to receive a single dose of either test sample 198 mg or reference samples 200 mg. The blood samples from the volunteers were collected to measure the plasma concentration of thiophine （ an active metabolite of racecadotril） by HPLC. The pharmacokinetic parameters were analyzed using DAS software （version 1.0）. Results： The main pharmacokinetic parameters of test and reference samples were as followed： AUC0-11b （1267 ±494） vs. （1 138 ±415）μg·h·L^-1（CI 102.3% ±120.1%）; Cmax（886± 334）vs. （744± 339）μg·h·L^-1（CI 101.7%±~145.4% ） ; Tmax（1.24 ±0. 84）vs. （1.15 ±0. 79）h （P 〉0.05）. Relative bioavailability of racecadotril orally disintegrating tablets was（ 114.6 ± 24.5） %. Conclusion ： The domestic raceadotril orally disintegrating tablets was bioequivalent to imported racecadotril capsules.