{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T03:43:20Z","timestamp":1770695000203,"version":"3.49.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This study was sponsored by SAIPH Pharma"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    In Tunisia, bioequivalence studies have been required for generic drug approval since 2008. This study aimed to assess the bioequivalence of vildagliptin and metformin fixed-dose combination (FDC) 850\/50\u00a0mg for a tested (Bi-Galvine) versus the approved reference products (Galvumet). A randomized, two-way, two-period, single oral dose, open-label, crossover, bioequivalence study with a washout period of 7 days to compare metformin\/vildagliptin film-coated tablets in 18 healthy Tunisian subjects aged between 18 and 50 years under fed conditions was conducted at the National Center Chalbi Belkahia of Pharmacovigilance. During each period, 20 blood samples were collected from each subject at pre-dosing (0.00) and between 0.25 and 24.00\u00a0h after dosing. The bioequivalence between the test (T) and reference (R) products required 90% confidence intervals (CIs) for the geometric least square (LS) mean T\/R ratio to be within 80\u2013125% for the pharmacokinetic parameters, maximum plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ), and Area Under the Curve from zero to 24\u00a0h (AUC\n                    <jats:sub>0\u201324\u00a0h<\/jats:sub>\n                    ). The 90% CIs of the geometric means of the T\/R ratios for C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u201324\u00a0h<\/jats:sub>\n                    for metformin were 92.01\u2013102.66% and 93.55\u2013101.80%, respectively; the corresponding results for vildagliptin were 96.03\u2013107.09% and 94.46\u2013101.92%, respectively. Other parameters, such as AUC\n                    <jats:sub>0-\u221e<\/jats:sub>\n                    , time to maximum concentration (T\n                    <jats:sub>max<\/jats:sub>\n                    ), and terminal half-life (t\n                    <jats:sub>1\/2<\/jats:sub>\n                    ), were comparable between the test and reference products. Adverse events (AEs), mainly hypoglycemia and loose stools events, were reported without relevant differences between the test and reference products. AEs were generally mild and transient. No severe or serious AEs occurred. The new generic drug product of metformin\/vildagliptin FDC 850\/50\u00a0mg demonstrated bioequivalence to the approved product and is therefore expected to provide similar therapeutic effects.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-34082-4","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T14:54:59Z","timestamp":1770389699000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioequivalence assessment between two formulations of a film-coated fixed-dose combination of metformin and vildagliptin\u00a0(850\/50mg) in healthy Tunisian subjects under fed conditions"],"prefix":"10.1038","volume":"16","author":[{"given":"Khouloud","family":"Ferchichi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emna","family":"Gaies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syrine","family":"Ben Hammamia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanene","family":"El Jebari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouna","family":"Daldoul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salma","family":"Ghorbel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Semia","family":"Srairi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami","family":"Guermazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousr","family":"Gorgi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilhem","family":"Boutiba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kahena","family":"Bouzid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimen","family":"Abbessi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riadh","family":"Daghfous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mouna","family":"Ben Sassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameh","family":"Trabelsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"issue":"3","key":"34082_CR1","first-page":"229","volume":"100","author":"S Mbarki","year":"2022","unstructured":"Mbarki, S. et al. EPIDEMIOLOGIE DU DIABETE SUCRE EN TUNISIE.Etude Hammam Sousse Sahloul heart study (HSHS 2). Tunis Med. 100(3), 229\u2013240 (2022).","journal-title":"Tunis Med."},{"key":"34082_CR2","unstructured":"Anonymous. Vildagliptin \/ Metformin Hydrochloride Accord | European Medicines Agency. n.d. Available from: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/vildagliptin-metformin-hydrochloride-accord [Last accessed: 12\/17\/2023]."},{"key":"34082_CR3","unstructured":"Anonymous. WMA - The World Medical Association-WMA Declaration of Helsinki \u2013 Ethical Principles for Medical Research Involving Human Participants. n.d. Available from: https:\/\/www.wma.net\/policies-post\/wma-declaration-of-helsinki\/ [Last accessed: 11\/28\/2025]."},{"key":"34082_CR4","unstructured":"Anonymous & ICH E6 Good Clinical Practice - Scientific Guideline | European Medicines Agency (EMA). (2002). Available from: https:\/\/www.ema.europa.eu\/en\/ich-e6-good-clinical-practice-scientific-guideline [Last accessed: 11\/28\/2025]."},{"key":"34082_CR5","unstructured":"Anonymous. Investigation of Bioequivalence - Scientific Guideline | European Medicines Agency. n.d. Available from: https:\/\/www.ema.europa.eu\/en\/investigation-bioequivalence-scientific-guideline [Last accessed: 12\/17\/2023]."},{"key":"34082_CR6","unstructured":"Anonymous Compendium.Ch. n.d. Available from: https:\/\/compendium.ch\/product\/1138799-galvumet-cpr-pell-50-850-mg\/mpro [Last accessed: 7\/22\/2024]."},{"key":"34082_CR7","unstructured":"Research, C. DE and. Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs \u2014 General Considerations. FDA; (2020). Available from: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/bioavailability-and-bioequivalence-studies-submitted-ndas-or-inds-general-considerations [Last accessed: 12\/17\/2023]."},{"issue":"1","key":"34082_CR8","first-page":"28","volume":"73","author":"P Sen","year":"2020","unstructured":"Sen, P. et al. Bioequivalence study of vildagliptin and Metformin fixed dose combinations in healthy volunteers. Indian Practitioner. 73 (1), 28\u201333 (2020).","journal-title":"Indian Practitioner"},{"issue":"2","key":"34082_CR9","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1023\/A:1011503032353","volume":"28","author":"S-C Chow","year":"2001","unstructured":"Chow, S-C. & Wang, H. On sample size calculation in bioequivalence trials. J. Pharmacokinet. Pharmacodyn. 28(2), 155\u2013169. https:\/\/doi.org\/10.1023\/A:1011503032353 (2001).","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"34082_CR10","unstructured":"Anonymous & ICH M10 on Bioanalytical Method Validation - Scientific Guideline | European Medicines Agency. n.d. Available from: https:\/\/www.ema.europa.eu\/en\/ich-m10-bioanalytical-method-validation-scientific-guideline [Last accessed: 12\/17\/2023]."},{"key":"34082_CR11","doi-asserted-by":"publisher","unstructured":"Denney, W., Duvvuri, S. & Buckeridge, C. Simple, automatic noncompartmental analysis: The PKNCA R Package. J. Pharmacokinet. Pharmacodyn. 42(1), 11\u2013107, S65. ISSN 1573\u20138744. https:\/\/doi.org\/10.1007\/s10928-015-9432-2, R package version 0.12.1, (2015). https:\/\/github.com\/humanpred\/pknca","DOI":"10.1007\/s10928-015-9432-2"},{"issue":"1","key":"34082_CR12","first-page":"65","volume":"77","author":"C Bhupathi","year":"2017","unstructured":"Bhupathi, C. & Vajjha, V. H. Sample size recommendation for a bioequivalent study. 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Diabetes Ther. 13 (6), 1215\u20131229. https:\/\/doi.org\/10.1007\/s13300-022-01269-1 (2022).","journal-title":"Diabetes Ther."},{"issue":"6","key":"34082_CR17","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1185\/03007990802114070","volume":"24","author":"Y-L He","year":"2008","unstructured":"He, Y-L. et al. Effect of food on the pharmacokinetics of a vildagliptin\/metformin (50\/1000\u00a0mg) fixed-dose combination tablet in healthy volunteers. Curr. Med. Res. Opin. 24 (6), 1703\u20131709. https:\/\/doi.org\/10.1185\/03007990802114070 (2008).","journal-title":"Curr. Med. Res. 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