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The established barrier was utilized to assess the absorption kinetics of three selected therapeutic compounds: Doxycycline, Ganciclovir, and its prodrug Valganciclovir, following the implementation of a thorough LC\u2010MS\/MS validation protocol. The co\u2010culture of Caco\u20102 cells, representing absorptive enterocytes, and HT\u201029 MTX cells, modeling goblet cells, enabled the in\u2010situ generation of a sufficiently thick mucus layer covering the entire cell monolayer. The presence of HT\u201029 MTX cells, which exhibit weaker tight junctions than enterocytes, contributed to the observed lower transepithelial electrical resistance (TEER) and higher FITC\u2010dextran flux. The permeability of all the compounds was higher when tested in the co\u2010culture system containing mucus\u2010generating cells, compared to the Caco\u20102 monoculture, demonstrating the impact of mucus on intestinal drug transport kinetics. The permeability of ganciclovir following its generation from the prodrug valganciclovir was significantly higher than the permeability of ganciclovir itself, as the active metabolite ganciclovir exhibited an enhanced transport rate compared to when administered without metabolic activation. The developed microfluidic\u2010based intestinal barrier model has demonstrated the capability to reliably simulate drug absorption and prodrug metabolism, and its impact on drug permeation kinetics across the small intestine.<\/jats:p>","DOI":"10.1002\/adhm.202500692","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T11:44:18Z","timestamp":1748346258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of Pro\u2010Drug Metabolism and Drug Permeability Kinetics in a Microphysiological In Vitro Model of the Human Small Intestinal Barrier Incorporating Mucus\u2010Generating Cells Coupled with LC\u2010MS\/MS Analysis"],"prefix":"10.1002","volume":"14","author":[{"given":"Sultan K.","family":"AlShmmari","sequence":"first","affiliation":[{"name":"Leibniz Institute of Photonic Technology Member of Leibniz Health Technologies Member of the Leibniz Centre for Photonics in Infection Research (LPI)  Albert\u2010Einstein\u2010Stra\u00dfe 9 07745 Jena Germany"},{"name":"College of Science &amp; General Studies Alfaisal University  Riyadh 11533 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roa S.","family":"Fardous","sequence":"additional","affiliation":[{"name":"College of Science &amp; General Studies Alfaisal University  Riyadh 11533 Saudi Arabia"},{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences Strathclyde University  Glasgow G4 0RE UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed A.","family":"ALHamamah","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine King Faisal University  Hufuf 31982 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Cialla\u2010May","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Photonic Technology Member of Leibniz Health Technologies Member of the Leibniz Centre for Photonics in Infection Research (LPI)  Albert\u2010Einstein\u2010Stra\u00dfe 9 07745 Jena Germany"},{"name":"Institute of Physical Chemistry (IPC) and Abbe Center of Photonics (ACP) Friedrich Schiller University Jena Member of the Leibniz Centre for Photonics in Infection Research (LPI)  Helmholtzweg 4 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Popp","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Photonic Technology Member of Leibniz Health Technologies Member of the Leibniz Centre for Photonics in Infection Research (LPI)  Albert\u2010Einstein\u2010Stra\u00dfe 9 07745 Jena Germany"},{"name":"Institute of Physical Chemistry (IPC) and Abbe Center of Photonics (ACP) Friedrich Schiller University Jena Member of the Leibniz Centre for Photonics in Infection Research (LPI)  Helmholtzweg 4 07743 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-2221","authenticated-orcid":false,"given":"Qasem","family":"Ramadan","sequence":"additional","affiliation":[{"name":"College of Science &amp; General Studies Alfaisal University  Riyadh 11533 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Zourob","sequence":"additional","affiliation":[{"name":"College of Science &amp; General Studies Alfaisal University  Riyadh 11533 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.20"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16010037"},{"key":"e_1_2_8_3_1","volume-title":"Human Physiology: An Integrated Approach","author":"Silverthorn D. 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