摘要
目的:评价健康成年男性受试者单次口服盐酸阿米替林片后的生物等效性和安全性。方法:本研究共选择健康受试者48例试验。试验采用采用单次给药、随机、开放、两制剂、两周期、自身交叉试验设计方法进行盐酸阿米替林片生物等效性试验,试验分空腹和餐后两部分,受试者随机分为2组,第1周期分别口服受试制剂或参比制剂,第2周期交叉给药,2个周期间隔时间21d。受试者禁食过夜至少10h后分别口服受试制剂或参比制剂25 mg,并于预定时间点采集血样。计算主要药动学参数:阿米替林和去甲替林,计算受试/参比制剂的90%置信区间。试验过程中行生命体征、实验室及心电图检查,并记录不良事件情况。48例受试者全部纳入安全分析集,48例正式试验者纳入符合方案集。结果:48例志愿者均完成试验。空腹组受试与参比制剂阿米替林的Cmax,AUC0-t,AUC0-∞比值90%置信区间分别在90.14%~110.83%,99.10%~107.56%,98.73%~107.44%。餐后组的受试与参比制剂阿米替林的Cmax,AUC0-t,AUC0-∞比值90%置信区间分别在90.34%~114.23%,98.07%~113.71%,97.69%~112.53%。上述数据满足生物等效发生标准。试验过程中有93例不良事件例数。其中,受试制剂发生不良事件47例次,参比制剂发生不良事件46例次。不良事件均为轻度,未发现严重不良事件。结论:国产盐酸阿米替林片与参比制剂等效,安全性和耐受性良好。
Objective: To evaluate the bioequivalence and safety of healthy adult male subjects after a single oral amitriptyline hydrochloride tablet. Methods: A total of 48 healthy subjects were selected for this study. The test uses a single-dose, random, open, two-agent, two-cycle, self-crossover design method for the bioequivalence test of amitriptyline hydrochloride tablets. The test is divided into two parts, fasting and postprandial. For the two groups, the test preparation or the reference preparation was orally administered in the first cycle, and the second cycle was cross-dosed, and the interval between the two cycles was 21 d. After fasting for at least 10 hours overnight, the subjects orally took 25 mg of the test preparation or reference preparation, and collected blood samples at predetermined time points. Calculate the main pharmacokinetic parameters: amitriptyline and nortriptyline, and calculate the 90 % confidence interval of the test/reference preparation. During the test, vital signs, laboratory and electrocardiogram examinations E-mail:houqiwei2000@163.com.were performed, and adverse events were recorded. All 48 subjects were included in the safety analysis set, and 48 formal trial participants were included in the compliance set. Results: All 48 volunteers completed the trial. The 90 % confidence intervals of the ratios of Cmax, AUC0-t, and AUC0-∞ of the test and reference preparation amitriptyline in the fasting group were 90.14 to 110.83 %, 99.10 to 107.56 %, and 98.73 to 107.44 %, respectively. The Cmax, AUC0-t, and AUC0-∞ ratios of the test and reference preparations amitriptyline in the postprandial group were 90 % with confidence intervals of 90.34 %~114.23 %, 98.07 %~113.71 %, and 97.69 %~112.53 %. The above data meet the criteria for bioequivalence. There were 93 adverse events during the trial. Among them, 47 adverse reactions occurred in the test preparations and 46 adverse reactions occurred in the reference preparations. Adverse events were mild and no serious adverse events were found
作者
侯奇伟
姜天阳
Hou Qiwei;Jiang Tianyang(Hu’nan Dongting Pharmaceutical Co.,Ltd.,Changde 415000,China)
出处
《广东化工》
CAS
2020年第10期44-45,43,共3页
Guangdong Chemical Industry
