奥美沙坦酯氢氯噻嗪片在中国健康受试者中的生物等效性和药代动力学研究  

Bioequivalence and pharmacokinetic study of olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects

作　　者：张琦琪 徐贤根 楼金芳 宋博凡 杨春光 朱光辉[5] 李挺[1,2] ZHANG Qi-qi;XU Xian-gen;LOU Jin-fang;SONG Bo-fan;YANG Chun-guang;ZHU Guang-hui;LI Ting(Clinical Research Unit,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China;Department of Anesthesiology and Perioperative Medicine,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China;Hangzhou Bio-Sincerity Pharma-Tech Co.,Ltd,Hangzhou 310000,Zhejiang Province,China;Beijing Yuanyan Pharmaceutical Technology Co.,Ltd,Beijing 100000,China;Department of Pharmacy,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China)

机构地区：[1]温州医科大学附属第二医院临床医学研究中心,浙江温州325000 [2]温州医科大学附属第二医院麻醉科,浙江温州325000 [3]杭州百诚医药科技股份有限公司,温州医科大学附属第二医院药学部,浙江温州310000 [4]北京元延医药科技股份有限公司,北京100000 [5]温州医科大学附属第二医院药学部,浙江温州325000

出　　处：《中国临床药理学杂志》2024年第11期1623-1627,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究2种奥美沙坦酯氢氯噻嗪片在中国健康受试者中的生物等效性及安全性。方法24例健康受试者按单中心、随机、开放、单剂量、两制剂、两序列、两周期、自身交叉对照设计先后进行空腹和餐后试验,随机交叉单次口服受试制剂和参比制剂(每片含奥美沙坦酯20 mg与氢氯噻嗪12.5 mg)。用LC-MS/MS法测定给药后不同时间血浆中奥美沙坦和氢氯噻嗪血药浓度。用WinNonlin 7.0软件进行奥美沙坦和氢氯噻嗪的非房室模型分析,计算药代动力学参数并进行生物等效性评价。结果空腹组受试制剂与参比制剂奥美沙坦的C_(max)分别为(798.35±206.78)和(664.52±168.25)ng·mL^(-1),AUC_(0-t)分别为(4430.71±1294.87)和(3976.67±1083.54)h·ng·mL^(-1),AUC_(0-∞)分别为(4551.67±1303.06)和(4090.37±1103.97)h·ng·mL^(-1);氢氯噻嗪C_(max)分别为(92.39±35.96)和(96.15±38.76)ng·mL^(-1),AUC_(0-t)分别为(548.69±217.11)和(564.41±208.68)h·ng·mL^(-1),AUC_(0-∞)分别为(603.04±228.59)和(619.26±223.27)h·ng·mL^(-1)。餐后组受试制剂与参比制剂奥美沙坦的C_(max)分别为(583.15±149.48)和(550.57±104.76)ng·mL^(-1),AUC_(0-t)分别为(3585.18±952.72)和(3292.19±904.58)h·ng·mL^(-1),AUC_(0-∞)分别为(3696.05±996.55)和(3396.30±923.41)h·ng·mL^(-1);氢氯噻嗪C_(max)分别为(70.30±17.88)和(74.70±21.65)ng·mL^(-1),AUC_(0-t)分别为(476.60±119.39)和(492.91±144.81)h·ng·mL^(-1),AUC_(0-∞)分别为(523.37±132.67)和(535.81±151.92)h·ng·mL^(-1)。2种制剂的奥美沙坦和氢氯噻嗪的空腹组和餐后组C_(max)、AUC_(0-t)、AUC_(0-∞)均在80.00%~125.00%。结论在中国健康受试者中,2种奥美沙坦酯氢氯噻嗪片具有生物等效性,且安全性良好。Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,singledose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random crossover fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:C_(max)were(798.35±206.78)and(664.52±168.25)ng·mL^(-1),AUC_(0-t)were(4430.71±1294.87)and(3976.67±1083.54)h·ng·mL^(-1),AUC_(0-∞)were(4551.67±1303.06)and(4090.37±1103.97)h·ng·mL^(-1).The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:C_(max)were(92.39±35.96)and(96.15±38.76)ng·mL^(-1),AUC_(0-t)were(548.69±217.11)and(564.41±208.68)h·ng·mL^(-1),AUC_(0-∞)were(603.04±228.59)and(619.26±223.27)h·ng·mL^(-1).In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:C_(max)were(583.15±149.48)and(550.57±104.76)ng·mL^(-1),AUC_(0-t)were(3585.18±952.72)and(3292.19±904.58)h·ng·mL^(-1),AUC_(0-∞)were(3696.05±996.55)and(3396.30±923.41)h·ng·mL^(-1).The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:C_(max)were(70.30±17.88)and(74.70±21.65)ng·mL^(-1),AUC_(0-t)were(476.60±119.39)and(492.91±144.81)h·ng·mL^(-1),AUC_(0-∞)were(523.37±132.67)and(535.81±151.92)h·ng·mL^(-1).In fasting and fed condition,the 90%confidence interval(90%CI)of C_(max),AUC_(0-t)and AUC_(0-�

关 键 词：奥美沙坦酯氢氯噻嗪片 药代动力学 血药浓度 生物等效性 液相色谱-串联质谱法 

分 类 号：R972.4[医药卫生—药品]