法莫替丁口腔崩解片生物等效性研究

Bioequivalence Study of Famotidine Orally Disintegrating Tablet in Chinese Healthy Volunteers

目的考察法莫替丁口腔崩解片（受试制剂）和法莫替丁片（参比制剂）在健康受试者的生物等效性。方法采用随机分组、自身交叉对照设计,清洗期7d。20名男性成年健康受试者空腹服药20mg,在服药前（0h）、服药后0.5,1,2,3,4,6,8,10,12及24h采血6mL,以固相提取-高效液相色谱法测定血浆药物浓度。以非房室模型计算药动学参数AUC0-t,ρmax,tmax,t1/2和CL/F,通过多因素方差分析、双单侧t检验判断两种制剂的生物等效性。结果血浆药物浓度测定方法灵敏、准确、精密。20名健康受试者服用受试制剂和参比制剂后的AUC0-t分别为（480.3±144.8）和（470.9±164.7）μg·h·L^-1,ρmax分别为（83.1±26.9）和（87.2±35.3）μg·L^-1,tmax分别为（2.6±1.3）和（2.7±0.9）h,t1/2分别为（2.8±0.3）和（2.8±0.4）h,CL/F分别为（42.1±13.2）和（43.5±13.4）L·h^-1。法莫替丁口腔崩解片相对法莫替丁片的生物利用度为103.0%（90%置信区间为86.7%～115.3%）。统计学分析表明,两种制剂生物等效。结论法莫替丁口腔崩解片与法莫替丁片具有生物等效性。

OBJECTIVE To investigate the bioequivalence of famotidine orally distintegrating tablets （ test formulation） and famotidine tablets （reference formulation） in Chinese healthy volunteers. METHODS A randomized, self-control, crossover design was adopted. The wash-out period was 7 d. 20 healthy male adult volunteers were administered famotidine 20 mg and blood samples were taken at 0,0. 5,1,2,3,4,6,8,10,12 and 24 h. Plasma famotidine concentrations were assayed by solid-phase extraction and HPLC method. The pharmacokinetic parameters including AUC0-t ,ρmax,tmax,t1/2 and CL/F were calculated by noncompartmental analysis. The bioequivalence of the two formulations was evaluated by analysis of variance and two one-sided t-test. RESULTS The HPLC method was sensitive, accurate and precise. The pharmacokinetic parameters of famotidine test and reference formulations were as follows ：AUC0-t （480. 3 ± 144. 8 ） and （470.9±164.7）μg·h·L^-1,ρmax（83.1±26.9） and （87.2±35.3）μg·L^-1,tmax（2.6±1.3） and （2.7±0.9） h,t1/2（2.8± 0. 4） and （2. 8±0. 3） h,CL/F（42. 1± 13.2） and （43.5 ± 13.4） L · h^-1 ,respectively. The relative bioavailability of farnotidine orally distintegrating tablets was 103.0% （90% CI：86.7% ～ 115.3% ）. The statistical analysis showed that the two formulations were bioequivalent. CONCLUSION The famotidine orally distintegrating tablets are bioequivalent with famotidine tablets.