奥美拉唑干混悬剂与肠溶片在中国健康受试者中的药代动力学比较研究(20 mg)  

Comparison of pharmacokinetics between omeprazole dry suspension and enteric-coated tablets in healthy Chinese subjects( 20 mg)

作　　者：李晓斌[1] 喻明[1] 隋鑫[1] 曹莹 陈璐 阚敏 庄菊香 吴秀君[1] 马然[1] 王华伟[1] 王文萍[1] LI Xiao-bin;YU Ming;SUI Xin;CAO Ying;CHEN Lu;KAN Min;ZHUANG Ju-xiang;WU Xiu-jun;MA Ran;WANG Hua-wei;WANG Wen-ping(Phase I Clinical Trial Ward,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning Province,China;Nanjing Healthnice Pharmaceuticals Co.,Ltd.,Nanjing 210009,Jiangsu Province,China)

机构地区：[1]辽宁中医药大学附属医院国家药物临床试验机构Ⅰ期临床病房,辽宁沈阳110032 [2]南京海纳制药有限公司,江苏南京210009

出　　处：《中国临床药理学杂志》2022年第13期1505-1509,共5页The Chinese Journal of Clinical Pharmacology

基　　金：辽宁中医药大学中药临床药理学科建设基金资助项目(辽中医校发2016-198);辽宁省“兴辽英才计划”基金资助项目(XLYC1802008);辽宁省中药临床药物代谢动力学重点实验室基金资助项目(辽科发2005-16);国家重点研发计划项目基金资助项目(2018YFC1311600)。

摘　　要：目的以健康受试者为对象进行单次及多次口服奥美拉唑干混悬剂(20 mg,Ⅰ)的药代动力学试验,明确单次和多次给药后的药代动力学特征,并以市售奥美拉唑镁肠溶片为参比制剂,进行药代动力学比较研究。方法用单中心、随机、两周期、两交叉、自身对照试验设计,空腹条件下入组28例受试者,随机分为2组,每周期连续用药7天,每天口服奥美拉唑干混悬剂20 mg或奥美拉唑镁肠溶片20 mg,在第1天及第7天服药前后和第5~6天服药前分别按方案进行药代动力学血样采集,采用LC-MS/MS技术测定血浆中奥美拉唑浓度,采用WinNonlin 7.0计算药代动力学参数,并进行两种制剂单多次给药后的药代动力学比较评价。结果受试者单次服用奥美拉唑受试制剂和参比制剂后血浆中的C_(max)分别为(914.00±420.65),(668.61±435.34)ng·mL^(-1),AUC_(0-24)分别为(1408.87±1599.59),(1417.82±1806.58)ng·h·mL^(-1),AUC_(0-∞)分别为(1416.42±1607.95),(1427.42±1824.80)ng·h·mL^(-1),C_(max)、AUC_(0-24)、AUC_(0-∞)的90%CI分别为125.66%~176.95%,95.89%~113.21%和95.95%~113.26%。多次给药后奥美拉唑(20 mg)受试制剂和参比制剂后AUC_(ss)的90%CI为91.14%~107.21%。结论奥美拉唑受试制剂和参比制剂(20 mg)口服给药后,AUC均生物等效,单次给药的C_(max)生物不等效,多次给药后稳态平均血药浓度生物不等效,受试制剂比参比制剂起效快,受试制剂的T_(max)小于参比制剂.Objective To determine the pharmacokinetic characteristics after single and multiple administrations of omeprazole dry suspensions in healthy volunteers,and compare pharmacokinetic properties of different fomulations of omeprazole(dry suspensions and tablets).Methods Using a single-center,randomized,two-cycle crossover trial design,healthy subjects were randomly divided into two groups of oral omeprazole dry suspension 20 mg or omeprazole magnesium enteric-coated tablets 20 mg to determine the concentration of omeprazole in plasma by LC-MS/MS technology,and the pharmacokinetic parameters was calculated and the bioequivalence was comapred by WinNonlin 7.0.Results The C_(max) of the test and reference preparations for single administration were(914.00±420.65),(668.61±435.34)ng·h·mL^(-1),AUC_(0-24) were(1408.87±1599.59),(1417.82±1806.58)ng·h·mL^(-1) AUC_(0-∞)were(1416.42±1607.95),(1427.42±1824.80)ng·h·mL^(-1).The 90% CI of C_(max),AUC_(0-t),and AUC_(0-∞)were 125.66%-176.95%,95.89%-113.21%,95.95%-113.26%,respectively.After multiple administration of 20 mg test and reference formulation of omeprazole,90% CI of AUCsswas 91.14%-107.21%.Conclusion After oral administration of test and reference preparation(20 mg)formulation of omeprazole,the AUC is bioequivalent,the Cmaxof single dose is not bioequivalent,and the steady-state average blood concentration after multiple doses is not bioequivalent.The test formulation takes effect faster than the reference formulation,because the Tmaxof the test formulation was smaller than the reference formulation.

关 键 词：奥美拉唑干混悬剂 健康受试者 药代动力学 生物等效性 

分 类 号：R975[医药卫生—药品]