克拉霉素分散片的健康人体生物等效性研究

Bioequivalence of clarithromycin dispersed tablet in health volunteers

目的:研究克拉霉素分散片在健康人体的药动学及生物等效性。方法:采用两制剂双周期双交叉前后自身对照试验设计。20名健康志愿者分别口服克拉霉素分散片受试制剂或参比制剂500 mg,采用高效液相色谱-质谱法(LC-MS)测定血浆中克拉霉素的浓度,经DAS 2.1软件处理后得药动学数据,并进行等效性检验。结果:受试制剂的t_(1/2)为(3.72±0.42)h,C_(max)为(2 350.7±604.2)ng·mL^(-1),T_(max)为(1.48±0.36)h,AUC_(0-t)为(12 425±1975)ng·h·mL^(-1);参比制剂的t_(1/2)为(4.22±1.15)h,C_(max)为(2 045。0±379.5)ng·mL^(-1),T_(max)为(1.76±0.52)h,AUC_(0-t)为(11 954±2 152)ng·h·mL^(-1)。以AUC_(0-t)计算,与参比制剂比较,受试制剂平均相对生物利用度为(101.7±7.3)%,AUC_(0-t),AUC_(0-∞)和C_(max)均拒绝生物不等效假设。结论:测定结果经方差分析及双单侧t检验,表明两种制剂具有生物等效性。

Objective：To study the pharmacokinetics and bioequivalence of clarithromycin dispersed tablet in healthy volunteers. Methods： In a randomized, crossover and self-control study, 20 healthy male volunteers were orally administrated with a single dose of clarithromycin dispersed tablet or the reference tablet （500 mg）. The plasma samples from the volunteers were collected to detect clarithromycin concentrations by the LC-MS method. The plasma concentration-time curves as well as bioequivalence of both clarithromycin dispersed tablet and reference tablet were analyzed using DAS 2.1 software. Results： The main pharmacokilletie parameters of the test and reference tablets were as follow： t,/2 were （3.72 ±0.42） and （4.22 ± 1.15）h; C were （2 350.7 ±604.2） and （ 2 045.0 ± 379.5 ） ng·h·mL-1 ; T were （ 1.48 ± 0.36） and （ 1.76 ± 0.52 ） h ; AUC0 -t, were （ 12 425 ± 1 975 ） and （ 11 954 ± 2 152） ng·h·mL-1 The relative bioavailability of the test tablet was （ 101.7 ± 7.3 ） %. Conclusion ： As analyzed with ANOVA and two-one-sided t-test, the reference anti test clarithromycin dispersed tablets are bio： equivalent.