氯雷他啶片剂及胶囊生物等效的研究

A STUDY ON BIOEQUIVALENCE OF LORATADINE TABLETS AND CAPSULES

①目的 评价受试制剂氯雷他啶片剂和胶囊与参比制剂市销氯雷他啶片 (开瑞坦 )是否生物等效 ,为申报新药及临床应用提供实验依据。②方法 选择 1 8名男性健康受试者 ,单剂三交叉口服试验制剂氯雷他啶片剂、氯雷他啶胶囊以及参比制剂开瑞坦各 2 0mg ,应用液质联用法测定服药前和服药后 0 .33、0 .6 7、1 .0 0、1 .5 0、2 .0 0、3.0 0、4 .0 0、6 .0 0、8.0 0、1 2 .0 0、2 4 .0 0h血药浓度 ,计算主要药动学参数 ,评价受试制剂与参比制剂的生物等效性。③结果 受试制剂氯雷他啶片剂、胶囊和参比制剂的AUC0～t分别为 38.79、38.4 0、37.0 2g·h·L-1 ,血药峰值浓度 (Cmax)分别为 1 3.73、1 3.76、1 3.91 μg/L ,血药峰值时间 (Tmax)分别为 1 .33、1 .1 7、1 .2 4h ,半衰期 (T1 /2 )分别为 4 .4 3、4 .90、4 .38h ,AUC0～∞ 分别为 4 0 .83、4 0 .6 7、38.74g·h·L-1 。受试制剂氯雷他啶片的相对生物利用度为1 0 4 .78% ,受试制剂氯雷他啶胶囊的相对生物利用度为 1 0 3.73%。AUC0～t、AUC0～∞ 和Cmax经双单侧t检验和 (1- 2α)置信区间检验无显著差异。

Objective\ To evaluate whether it was of bioequivalence between tested loratadine tablets , capsules and market sale loratadine tablets(clarityne), so as to provide the trial evidence for declaring the new drug and its clinical application. Methods\ Single dose of 20 mg of domestic loratadine tablets or capsules or imported loratadine(clarityne) was given to 18 healthy male volunteers. The blood samples were detected for its concentration, before and at 0.33, 0.67, 1.00, 1.50, 2.00, 3.00, 4.00 , 6.00, 8.00, 12.00, 24.00 hours after medication, by LC/MS/MS method. The pharmacokinetic parameters were calculated and bioequivalence of tested and market sale loratadine evaluated. \ Results\ The main pharmacokinetic parameters of loratadine tablets and capsules and imported loratadine(clarityne) were as follows: AUC 0～ t : 38.79, 38.40 and 37.02 g·h·L -1 ; C max : 13.73 , 13.76 and 13.91 μg/L; T max : 1.33, 1.17 and 1.24 h; T 1/2 : 4.43, 4.90 and 4.38 h, respectively. There were no significant differences in the parameters between the tested and comparative preparations. The relative bioequivailability of domestic loratadine tablets and capsules was 104.78% and 103.73%, respectively. \ Conclusion\ The results of statistical analysis showed that the tested and comparative preparations were bioequivalence.