{"title":"两种盐酸二甲双胍片在空腹和空腹条件下的生物等效性及药代动力学评价。","authors":"Yuxing Huang, Qiuhan Cai, Meifang Li, Shengxuan Guo, Gaiying Dong, Siyuan Hu, Chengliang Zhong","doi":"10.1007/s13318-025-00961-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>With diabetes prevalence rising and original formulations unable to meet demand, establishing generic equivalence is crucial for treatment accessibility. This study evaluated the bioequivalence of generic metformin hydrochloride (0.25 g) versus the reference drug in Chinese volunteers under fasting and fed conditions.</p><p><strong>Methods: </strong>In this randomized, open-label, two-period crossover trial, 26 healthy volunteers per group received single doses under fasting and fed conditions. Plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, pharmacokinetic metrics were calculated using the WinNonlin 6.3 software, and bioequivalence was evaluated using SAS 9.4.</p><p><strong>Results: </strong>Under fasting conditions, the geometric mean ratios (GMRs) between the test and reference groups were 103.12% (C<sub>max</sub>), 103.65% (AUC<sub>0-t</sub>), and 103.31% (AUC<sub>0-∞</sub>), with 90% CIs of 92.64-114.78%, 96.04-111.85%, and 96.00-111.17%, respectively. Fed conditions yielded GMRs of 93.98% (C<sub>max</sub>), 97.34% (AUC<sub>0-t</sub>), and 96.97% (AUC<sub>0-∞</sub>), with 90% CIs of 89.42-98.78%, 92.72-102.18%, and 92.40-101.78%, respectively. All these parameters met bioequivalence criteria (80-125%). Median T<sub>max</sub> was delayed under fed conditions (2.125 h vs. 4.000 h), with consistent food effects (reduced C<sub>max</sub> and AUC) and safety profiles between formulations.</p><p><strong>Conclusion: </strong>These results demonstrate that the generic metformin formulation is bioequivalent to the innovative product and well tolerated in Chinese healthy volunteers under both fasting and fed conditions.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":"50 5","pages":"431-440"},"PeriodicalIF":2.4000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394267/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers.\",\"authors\":\"Yuxing Huang, Qiuhan Cai, Meifang Li, Shengxuan Guo, Gaiying Dong, Siyuan Hu, Chengliang Zhong\",\"doi\":\"10.1007/s13318-025-00961-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>With diabetes prevalence rising and original formulations unable to meet demand, establishing generic equivalence is crucial for treatment accessibility. This study evaluated the bioequivalence of generic metformin hydrochloride (0.25 g) versus the reference drug in Chinese volunteers under fasting and fed conditions.</p><p><strong>Methods: </strong>In this randomized, open-label, two-period crossover trial, 26 healthy volunteers per group received single doses under fasting and fed conditions. Plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, pharmacokinetic metrics were calculated using the WinNonlin 6.3 software, and bioequivalence was evaluated using SAS 9.4.</p><p><strong>Results: </strong>Under fasting conditions, the geometric mean ratios (GMRs) between the test and reference groups were 103.12% (C<sub>max</sub>), 103.65% (AUC<sub>0-t</sub>), and 103.31% (AUC<sub>0-∞</sub>), with 90% CIs of 92.64-114.78%, 96.04-111.85%, and 96.00-111.17%, respectively. Fed conditions yielded GMRs of 93.98% (C<sub>max</sub>), 97.34% (AUC<sub>0-t</sub>), and 96.97% (AUC<sub>0-∞</sub>), with 90% CIs of 89.42-98.78%, 92.72-102.18%, and 92.40-101.78%, respectively. All these parameters met bioequivalence criteria (80-125%). Median T<sub>max</sub> was delayed under fed conditions (2.125 h vs. 4.000 h), with consistent food effects (reduced C<sub>max</sub> and AUC) and safety profiles between formulations.</p><p><strong>Conclusion: </strong>These results demonstrate that the generic metformin formulation is bioequivalent to the innovative product and well tolerated in Chinese healthy volunteers under both fasting and fed conditions.</p>\",\"PeriodicalId\":11939,\"journal\":{\"name\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"volume\":\"50 5\",\"pages\":\"431-440\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394267/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Drug Metabolism and Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13318-025-00961-4\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Drug Metabolism and Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13318-025-00961-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/21 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers.
Background and objectives: With diabetes prevalence rising and original formulations unable to meet demand, establishing generic equivalence is crucial for treatment accessibility. This study evaluated the bioequivalence of generic metformin hydrochloride (0.25 g) versus the reference drug in Chinese volunteers under fasting and fed conditions.
Methods: In this randomized, open-label, two-period crossover trial, 26 healthy volunteers per group received single doses under fasting and fed conditions. Plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, pharmacokinetic metrics were calculated using the WinNonlin 6.3 software, and bioequivalence was evaluated using SAS 9.4.
Results: Under fasting conditions, the geometric mean ratios (GMRs) between the test and reference groups were 103.12% (Cmax), 103.65% (AUC0-t), and 103.31% (AUC0-∞), with 90% CIs of 92.64-114.78%, 96.04-111.85%, and 96.00-111.17%, respectively. Fed conditions yielded GMRs of 93.98% (Cmax), 97.34% (AUC0-t), and 96.97% (AUC0-∞), with 90% CIs of 89.42-98.78%, 92.72-102.18%, and 92.40-101.78%, respectively. All these parameters met bioequivalence criteria (80-125%). Median Tmax was delayed under fed conditions (2.125 h vs. 4.000 h), with consistent food effects (reduced Cmax and AUC) and safety profiles between formulations.
Conclusion: These results demonstrate that the generic metformin formulation is bioequivalent to the innovative product and well tolerated in Chinese healthy volunteers under both fasting and fed conditions.
期刊介绍：
Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences.
Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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