Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution

Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution Valdirene Santos, Leticia Ramos Dantas, Gabriel Burato Ortis, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9281224/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, driven by antibiotic-induced dysbiosis and toxin production. Oral vancomycin is the recommended first-line therapy; however, the conventional formulation is acid-labile and may undergo gastric degradation, potentially affecting colonic drug delivery. Gastro-resistant formulations may improve targeted intestinal release and reduce interindividual variability in drug exposure. Objectives : To compare fecal vancomycin exposure and variability between a gastro-resistant capsule formulation and conventional oral vancomycin administered as an aqueous solution in healthy volunteers. Methods : This prospective, Phase 1 experimental study comprised laboratory and clinical components. Vancomycin stability across pH conditions was assessed, and a high-performance liquid chromatography (HPLC) method for fecal quantification was developed and validated. Ten healthy adults received vancomycin 125 mg every 6 hours for 48 hours, either as gastro-resistant capsules (VanCGR, n=5) or conventional oral solution (VanAD, n=5). Fecal samples were collected after dosing and analyzed for vancomycin concentration. Statistical analyses were primarily descriptive, with comparisons performed using appropriate parametric or non-parametric tests. Results : The HPLC method demonstrated excellent selectivity, linearity (r² ≥0.98), precision, accuracy, and stability. Both formulations achieved fecal vancomycin concentrations far exceeding the minimum inhibitory concentration for C. difficile . Mean fecal concentrations were higher in the VanAD group (4,446.64 µg/g) compared with the VanCGR group (2,784.27 µg/g). However, VanCGR demonstrated lower interindividual variability and a more homogeneous exposure profile. Conclusions : Gastro-resistant vancomycin capsules achieved therapeutically adequate fecal concentrations with reduced variability compared with conventional oral solution. These findings support gastro-resistant delivery as a promising strategy to optimize colonic vancomycin exposure and warrant further evaluation in randomized clinical trials involving patients with active CDI. Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9281224","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":616025231,"identity":"a37aadc2-0764-4b2e-b66a-72080311fc79","order_by":0,"name":"Valdirene Santos","email":"","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":false,"prefix":"","firstName":"Valdirene","middleName":"","lastName":"Santos","suffix":""},{"id":616025232,"identity":"595ab5c9-fd2e-4475-8b9c-709bec803f57","order_by":1,"name":"Leticia Ramos Dantas","email":"","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":false,"prefix":"","firstName":"Leticia","middleName":"Ramos","lastName":"Dantas","suffix":""},{"id":616025233,"identity":"d6269d27-d15d-4adb-aa8c-d7b1f2a44864","order_by":2,"name":"Gabriel Burato Ortis","email":"","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":false,"prefix":"","firstName":"Gabriel","middleName":"Burato","lastName":"Ortis","suffix":""},{"id":616025234,"identity":"b19bcc42-9447-4f3e-b2a8-3fdb6cfc89f3","order_by":3,"name":"Paula Hansen Suss","email":"","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":false,"prefix":"","firstName":"Paula","middleName":"Hansen","lastName":"Suss","suffix":""},{"id":616025235,"identity":"8ea0710e-48eb-44d1-871a-99f195cd37c4","order_by":4,"name":"João Victor de Oliveira Eloi de Souza","email":"","orcid":"","institution":"Federal University of Rio de Janeiro","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"Victor de Oliveira Eloi","lastName":"de Souza","suffix":""},{"id":616025236,"identity":"2a41d4c3-777c-4114-93a8-45e98d0455ec","order_by":5,"name":"Rita Estrela","email":"","orcid":"","institution":"Federal University of Rio de Janeiro","correspondingAuthor":false,"prefix":"","firstName":"Rita","middleName":"","lastName":"Estrela","suffix":""},{"id":616025237,"identity":"d04a1fca-18f0-4d67-bfb2-d0306e747cd6","order_by":6,"name":"Edlaine Rijo Costa","email":"","orcid":"","institution":"Federal University of Rio de Janeiro","correspondingAuthor":false,"prefix":"","firstName":"Edlaine","middleName":"Rijo","lastName":"Costa","suffix":""},{"id":616025238,"identity":"1e3d2e44-718d-4a0c-9ca0-38bb4df58bde","order_by":7,"name":"Fernanda L. Moreira","email":"","orcid":"","institution":"Federal University of Rio de Janeiro","correspondingAuthor":false,"prefix":"","firstName":"Fernanda","middleName":"L.","lastName":"Moreira","suffix":""},{"id":616025239,"identity":"057e0412-3ce3-4a1d-a0fc-d74d04d830cb","order_by":8,"name":"Felipe Francisco Tuon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBAC9gbmhgNQNuMDCM2DXwvPAUawFgkgZjYgWgsDVAubBHFa2BsbDxdUMNQZHO89Vl3YZpdn3sB77ANeLTwHGw7POMMgYXDmXNrtmW3JxTIH+JJn4NNiL5HYcJi3DajlRo7Zbd62A4kzGHiM8TtM/iFQyz+IlmLitEgwArU0QLQwE6eFB+iwGcckJGeeOWMsPeNccrEEM18yfi3shw9/Lqix4ec73mP4uaDMLk+CvfcwXi0gwAyJFjCDIQFMEqEFwUggQsMoGAWjYBSMMAAALapEH8YL460AAAAASUVORK5CYII=","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":true,"prefix":"","firstName":"Felipe","middleName":"Francisco","lastName":"Tuon","suffix":""}],"badges":[],"createdAt":"2026-03-31 14:26:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9281224/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9281224/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106403930,"identity":"f8002117-44a4-46da-8778-8afd3e69220b","added_by":"auto","created_at":"2026-04-08 09:15:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":456402,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9281224/v1_covered_68526771-edd7-46c1-83bf-10391830cf1f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9281224/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9281224/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: \u003cem\u003eClostridioides difficile\u003c/em\u003e infection (CDI) is a leading cause of healthcare-associated diarrhea, driven by antibiotic-induced dysbiosis and toxin production. Oral vancomycin is the recommended first-line therapy; however, the conventional formulation is acid-labile and may undergo gastric degradation, potentially affecting colonic drug delivery. Gastro-resistant formulations may improve targeted intestinal release and reduce interindividual variability in drug exposure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e: To compare fecal vancomycin exposure and variability between a gastro-resistant capsule formulation and conventional oral vancomycin administered as an aqueous solution in healthy volunteers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This prospective, Phase 1 experimental study comprised laboratory and clinical components. Vancomycin stability across pH conditions was assessed, and a high-performance liquid chromatography (HPLC) method for fecal quantification was developed and validated. Ten healthy adults received vancomycin 125 mg every 6 hours for 48 hours, either as gastro-resistant capsules (VanCGR, n=5) or conventional oral solution (VanAD, n=5). Fecal samples were collected after dosing and analyzed for vancomycin concentration. Statistical analyses were primarily descriptive, with comparisons performed using appropriate parametric or non-parametric tests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The HPLC method demonstrated excellent selectivity, linearity (r² ≥0.98), precision, accuracy, and stability. Both formulations achieved fecal vancomycin concentrations far exceeding the minimum inhibitory concentration for \u003cem\u003eC. difficile\u003c/em\u003e. Mean fecal concentrations were higher in the VanAD group (4,446.64 µg/g) compared with the VanCGR group (2,784.27 µg/g). However, VanCGR demonstrated lower interindividual variability and a more homogeneous exposure profile.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Gastro-resistant vancomycin capsules achieved therapeutically adequate fecal concentrations with reduced variability compared with conventional oral solution. These findings support gastro-resistant delivery as a promising strategy to optimize colonic vancomycin exposure and warrant further evaluation in randomized clinical trials involving patients with active CDI.\u003c/p\u003e","manuscriptTitle":"Comparative Fecal Pharmacokinetics of Vancomycin Delivered by Gastro-Resistant Capsules and Oral Solution","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 06:13:59","doi":"10.21203/rs.3.rs-9281224/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"45d969a5-8fd0-43df-ba96-10037bba2390","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T06:13:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 06:13:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9281224","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9281224","identity":"rs-9281224","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}