两种厄贝沙坦氢氯噻嗪片在中国健康受试者体内的生物等效性被引量：2

Bioequivalence of two irbesartan hydrochlorothiazide tablets in healthy volunteers in China

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摘要目的研究两种厄贝沙坦氢氯噻嗪片在中国健康受试者体内的生物等效性。方法空腹试验和餐后试验各入组32例健康受试者,随机、开放、2周期、双交叉单剂量口服厄贝沙坦氢氯噻嗪片(150 mg/12.5 mg)受试制剂和参比制剂,采用液相色谱串联质谱(LC-MS/MS)法测定给药后不同时间点厄贝沙坦及氢氯噻嗪的血药浓度。采用Phoenix Win Nonlin 7.0软件计算药动学参数,考察两制剂生物等效性。结果空腹试验中受试制剂和参比制剂厄贝沙坦的药动学参数c_(max)分别为2 618.1和2 756.4 ng·mL^(-1),AUC_(0-t)分别为10 643.2和10 552.4 ng·h·mL^(-1),AUC_(0-∞)分别为11 126.7和11 000.4 ng·h·mL^(-1);氢氯噻嗪的药动学参数c_(max)分别为108.1和108.8 ng·mL^(-1),AUC_(0-t)分别为626.4和633.5 ng·h·mL^(-1),AUC_(0-∞)分别为649.6和651.3 ng·h·mL^(-1)。餐后试验中受试制剂和参比制剂厄贝沙坦的药动学参数c_(max)分别为2 712.3和2 823.1 ng·mL^(-1),AUC_(0-t)分别为9 887.2和10 006.7 ng·h·mL^(-1),AUC_(0-∞)分别为10 473.4和10 454.7 ng·h·mL^(-1);氢氯噻嗪的药动学参数c_(max)分别为79.3和85.1 ng·mL^(-1),AUC_(0-t)分别为601.2和624.6 ng·h·mL^(-1),AUC_(0-∞)分别为620.4和643.8 ng·h·mL^(-1)。受试制剂与参比制剂c_(max)、AUC_(0-t)和AUC_(0-∞)几何均数比值的90%置信区间均在87.23%~109.31%之间。结论两种厄贝沙坦氢氯噻嗪片在中国健康受试者体内具有生物等效性。 AIM To study the bioequivalence of two irbesartan hydrochlorothiazide tablets in healthy Chinese subjects.METHODS The fasting test and the fed test each enrolled 32 healthy subjects in a random,open,2-period,double-crossover single-dose oral irbesartan hydrochlorothiazide tablets (150 mg/12.5 mg) test and reference preparations.The plasma concentrations of irbesartan and hydrochlorothiazide at different time points were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS).The pharmacokinetic parameters were calculated and the bioequivalence was compared by Phoenix Win Nonlin 7.0 program.RESULTS The pharmacokinetic parameters for test and reference preparations in fasting condition were as follows:irbesartan c_(max) were 2 618.1 and 2 756.4 ng·mL^(-1),AUC_(0-t) were10 643.2 and 10 552.4 ng·h·mL^(-1),AUC_(0-∞)were 11 126.7 and 11 000.4 ng·h·mL^(-1),respectively.Hydrochlorothiazide c_(max) were 108.1 and 108.8 ng·h·mL^(-1),AUC_(0-t) were 626.4 and 633.5 ng·h·mL^(-1),AUC_(0-∞)were 649.6 and 651.3 ng·h·mL^(-1),respectively.The pharmacokinetic parameters for test and reference preparations in fed condition were as follows:irbesartan c_(max) were 2 712.3 and 2 823.1 ng·mL^(-1),AUC_(0-t) were 9 887.2 and 10 006.7 ng·h·mL^(-1),AUC_(0-∞)were 10 473.4 and 10 454.7 ng·h·mL^(-1),respectively.Hydrochlorothiazide c_(max) were 79.3 and 85.1 ng·mL^(-1),AUC_(0-t) were 601.2 and 624.6 ng·h·mL^(-1),AUC_(0-∞)were 620.4 and 643.8 ng·h·mL^(-1),respectively.The 90%confidence intervals of the geometric mean ratios of c_(max),AUC_(0-t),AUC_(0-∞)for the test preparation and the reference preparation were all between 87.23%and 109.31%.CONCLUSION The two irbesartan hydrochlorothiazide tablets are bioequivalent in Chinese healthy subjects.

作者隋鑫李晓斌王华伟曹莹洪磊王力王文萍 SUI Xin;LI Xiao-bin;WANG Hua-wei;CAO Ying;HONG Lei;WANG Li;WANG Wen-ping(PhaseⅠClinical Trial Center,Affiliated Hospital of Liaoning University of Chinese Medicine,Shenyang LIAONING 110032,China;Hubei Jingjiangyuan Pharmaceutical Co.,LTD.,Jingzhou HUBEI 434400,China)

机构地区辽宁中医药大学附属医院Ⅰ期临床研究室湖北荆江源制药股份有限公司

出处《中国新药与临床杂志》 CAS CSCD 北大核心 2021年第1期34-39,共6页 Chinese Journal of New Drugs and Clinical Remedies

基金国家重点研发计划项目(2018YFC1311600) 辽宁省“兴辽英才计划”(XLYC1802008) 国家中医药管理局中药临床药理学科建设项目辽宁中医药大学中药临床药理学科建设项目辽宁省中药临床药物代谢动力学重点实验室资助项目。