摘要
目的研究两种那格列奈片剂的人体相对生物利用度,评价其生物等效性。方法选择20名健康男性志愿者,按照两制剂两周期的随机交叉试验设计,分别单剂量口服参比制剂(普通片)和受试制剂(分散片),剂量均为120 mg,采用液相色谱-串联质谱(LC-MS/MS)法测定其血浆中那格列奈的质量浓度,用DAS 1.0软件计算各药物代谢动力学参数并进行生物等效性统计分析。结果受试制剂和参比制剂的主要药物代谢动力学参数,峰浓度(Cmax)分别为(9.1±1.7)μg/mL和(7.7±2.1)mg/L,达峰时间(tmax)分别为(0.7±0.3)h和(1.9±1.1)h,0～10 h药时曲线下面积(AUC0-10)分别为(19.7±4.0)mg/(L.h)和(20.8±3.0)mg/(L.h),0～∞药时曲线下面积(AUC0-∞)分别为(20.0±4.1)μg/(mL.h)和(21.3±3.3)mg/(L.h),半衰期(t1/2)分别为(1.7±0.2)h和(1.6±0.2)h。两制剂的Cmax,tmax,AUC0-∞均存在显著性差异。双单侧t检验结果表明,受试制剂Cmax的90%置信区间落在参比制剂的75%～133%范围内,AUC的90%置信区间均落在参比制剂的80%～125%范围内,相对生物利用度为(94.9±14.4)%。结论两制剂具有生物等效性。
Objective To evaluate the relative bioequivalence of two kinds of nateglinide tablets in healthy male volunteers.Methods In a randomized crossover design,20 healthy male volunteers were given a single oral dose of the test preparation（dispersible tablets） or reference preparation（common tablets）,the dose was 120 mg of nateglinide for the two preparations.The concentrations of nateglinide in human plasma were determined by the LC-MS/MS method.Results The main pharmacokinetic parameters of the test and reference nateglinide tablets were as follows：Cmax were（9.1±1.7）ng/mL and（7.7±2.1）ng/mL,tmax were（0.7±0.3）h and（1.9±1.1） h,AUC0-10 h were（19.7±4.0）ng/mL and（20.8±3.0）ng/mL·h,AUC0-∞were（20.0±4.1）ng/mL·h and（21.3±3.3）ng/mL·h,and t1/2 were（1.7±0.2）h and（1.6±0.2）h,respectively.The relative bioavailability of the test dispersible tablet was（94.9±14.4）%.There was significant difference in Cmax,tmax,and AUC0-∞between the two preparations.Two one-sided t test Results showed that the 90%confidential interval of Cmax and AUC in the test preparation were under the range of 75%-133%and the range of 80%-125%in the reference preparation respectively.The relative bioavailability of the test preparation was（94.9±14.4） %.Conclusion The two preparations were bioequivalent.
出处
《中国药业》
CAS
2012年第15期24-26,共3页
China Pharmaceuticals
