| 引用本文: | 李鹏洲,杨航,黄乐群,边崇安,王晖,李荣.酒石酸伐尼克兰在中国健康受试者中的药代动力学和生物等效性研究[J].中国现代应用药学,2025,42(21):95-100. |
| li pengzhou,yang hang,hang lequn,bian chongan,wang hui,li rong.Pharmacokinetics and bioequivalence study of varenicline tartrate in healthy Chinese subjects[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(21):95-100. |
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| 摘要: |
| 目的：评价中国健康受试者空腹及餐后单次口服酒石酸伐尼克兰受试制剂和参比制剂的生物等效性。
方法：采用单中心、随机、开放、单次给药、两周期、双交叉试验设计，空腹及餐后组受试者各24例，每周期口服受试制剂或参比制剂1mg，采用LC-MS/MS法测定伐尼克兰血药浓度，WinNonlin 8.1软件计算药动学参数，并进行生物等效性评价。
结果：空腹组受试制剂与参比制剂的药动学参数Cmax分别为(5.73±1.23)、(5.47±1.05) ng·mL-1；AUC0-t分别为(107.57±17.70)、(111.78±25.29) h·ng·mL-1；AUC0-∞分别为(111.48±18.87)、(116.33±27.74) h·ng·mL-1；Tmax分别为1.50、1.50 h；t1/2分别为(20.37±4.14)、(20.23±3.81) h；餐后组受试制剂与参比制剂的药动学参数Cmax分别为(5.88±1.02)、(6.26±1.13) ng·mL-1；AUC0-t分别为(107.72±19.15)、(114.24±27.11) h·ng·mL-1；AUC0-∞分别为(119.52±30.10)、(112.04±20.75) h·ng·mL-1；Tmax分别为2.00、2.00 h；t1/2分别为(21.39±3.79)、(22.19±4.50) h。ABE方法显示空腹Cmax、AUC0-t、AUC0-∞的置信区间为97.88~111.60%，92.33~103.60%，91.92~103.61%；餐后Cmax、AUC0-t、AUC0-∞的置信区间为87.63~101.74%，88.63~104.53%，88.05~104.31%，均满足置信区间在80~125%的要求。
结论：酒石酸伐尼克兰受试制剂T与参比制剂R在空腹和餐后状态下均具有生物等效性 |
| 关键词: 酒石酸伐尼克兰 生物等效性 药代动力学 LC/MS-MS |
| DOI： |
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| 基金项目:湖南省自然科学基金（2023TP1014） |
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| Pharmacokinetics and bioequivalence study of varenicline tartrate in healthy Chinese subjects |
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li pengzhou1, yang hang2, hang lequn3, bian chongan3, wang hui1, li rong1
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1.Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, Department of Pharmacy, Institute of Pharmacy and Pharmacology，the Second Affiliated Hospital, Hengyang Medical School, University of South China;2.Medical nsurance departement, The second affiliated hospital of university of south china;3.Sinobiopharma, Inc.
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| Abstract: |
| Objective: To evaluate the bioequivalence of the test and reference formulations of varenicline tartrate in healthy Chinese subjects under fasting and fed conditions.
Methods: This study employed a single-center, randomized, open-label, single-dose, two-period, two-sequence crossover design. A total of 24 subjects were enrolled in each group (fasting and fed), and each subject received a 1mg dose of either the test or reference formulation in each period. Varenicline plasma concentrations were measured using LC-MS/MS, and pharmacokinetic parameters were calculated using WinNonlin 8.1 software to assess bioequivalence.
Results: In the fasting group, the pharmacokinetic parameters of the test and reference formulations were as follows: Cmax: (5.73 ± 1.23) ng·mL-1 vs. (5.47 ± 1.05) ng·mL-1, AUC???: (107.57 ± 17.70) h·ng/mL vs. (111.78 ± 25.29) h·ng·mL-1, AUC??∞: (111.48 ± 18.87) h·ng·mL-1 vs. (116.33 ± 27.74) h·ng·mL-1, Tmax: 1.50 h vs. 1.50 h, t?/?: (20.37 ± 4.14) h vs. (20.23 ± 3.81) h. In the fed group, the pharmacokinetic parameters for the test and reference formulations were: Cmax: (5.88 ± 1.02) ng·mL-1 vs. (6.26 ± 1.13) ng·mL-1, AUC0-t: (107.72 ± 19.15) h·ng·mL-1 vs. (114.24 ± 27.11) h·ng·mL-1, AUC0-∞: (119.52 ± 30.10) h·ng·mL-1 vs. (112.04 ± 20.75) h·ng·mL-1, Tmax: 2.00 h vs. 2.00 h, t?/?: (21.39 ± 3.79) h vs. (22.19 ± 4.50) h. The average bioequivalence (ABE) method indicated that the 90% confidence intervals (CIs) for Cmax, AUC0??, and AUC0?∞ under fasting conditions were 97.88~111.60, 92.33~103.60, and 91.92~103.61, respectively. Under fed conditions, the corresponding CIs were 87.63~101.74, 88.63~104.53, and 88.05~104.31, all within the acceptable range of 80~125%.
Conclusion: The test formulation of Varenicline Tartrate (T) is bioequivalent to the reference formulation (R) under both fasting and fed conditions. |
| Key words: varenicline tartrate bioequivalence pharmacokinetics LC-MS/MS |
