中国临床药理学杂志2024，Vol.40Issue(11)：1623-1627,5.DOI:10.13699/j.cnki.1001-6821.2024.11.017
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
张琦琪 1徐贤根 2楼金芳 3宋博凡 3杨春光 4朱光辉 5李挺6
作者信息
- 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,浙江杭州 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
- 6. 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||温州医科大学附属第二医院麻醉科,浙江温州 325000
- 折叠
摘要
Abstract
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,single-dose,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 cross-over 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:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ 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:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ 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 Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.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Key words
olmesartan medoxomil and hydrochlorothiazide tablet/pharmacokinetics/plasma concentration/bioequivalence/liquid chromatography-mass spectrometry/mass spectrometry分类
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张琦琪,徐贤根,楼金芳,宋博凡,杨春光,朱光辉,李挺..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[J].中国临床药理学杂志,2024,40(11):1623-1627,5.
