{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:39:47Z","timestamp":1791549587494,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) are breakthrough medicines for obesity treatment and have rapidly gained widespread clinical application. Although GLP\u20101RAs are generally not associated with drug\u2013drug interactions (DDIs) via drug metabolism or transporter pathways, their effects on reduced gastrointestinal (GI) motility could influence the pharmacokinetics of coadministered oral medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study uses physiologically based pharmacokinetic (PBPK) modeling to evaluate the DDI potential of GLP\u20101RA\u2010induced GI motility delays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using Certara's Simcyp\u2122 Simulator V23, we modeled the pharmacokinetics of atorvastatin, metformin, metoprolol, ethinyl estradiol, and digoxin in a virtual cohort of obese adults (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091000). GLP\u20101RA\u2010related gastric emptying delays were simulated based on capsule endoscopy data from liraglutide\u2010treated patients. Results were compared with clinical data from semaglutide and liraglutide users. Additionally, exploratory analyses were conducted on frequently coadministered drugs identified from the 2022 Medical Expenditure Panel Survey, including rosuvastatin and dabigatran.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GLP\u20101RA\u2010induced gastric emptying delays led to increased area under the concentration\u2013time curve (AUC) and prolonged time to maximum concentration (Tmax) for several medications. The model outputs for rosuvastatin, valsartan, and dabigatran indicate increases in AUC by 64%, 90%, and 205%, respectively. Dabigatran, a narrow therapeutic index anticoagulant, exhibited the most significant changes, raising potential concerns of higher drug exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PBPK modeling suggests that GLP\u20101RAs can influence the pharmacokinetics of oral medications by delaying gastric emptying, potentially leading to clinically relevant DDIs. While further clinical validation and pharmacovigilance is needed, these findings highlight the importance of PBPK tools in predicting and potentially mitigating risks associated with GLP\u20101RA use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.70007","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T02:56:24Z","timestamp":1740538584000},"page":"211-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["GLP\u20101RA\u2010induced delays in gastrointestinal motility: Predicted effects on coadministered drug absorption by PBPK analysis"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0537-8702","authenticated-orcid":false,"given":"Levi","family":"Hooper","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-4843","authenticated-orcid":false,"given":"Shuhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-5034","authenticated-orcid":false,"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-022-02394-w"},{"key":"e_1_2_9_3_1","unstructured":"Medical Expenditure Panel Survey (MEPS).Agency for Healthcare Research and Quality Rockville MD.2024https:\/\/www.ahrq.gov\/data\/meps.html"},{"key":"e_1_2_9_4_1","unstructured":"Global Data.Glucagon\u2010Like Peptide 1 Receptor (GLP\u20101R) agonists in type 2 diabetes and obesity in major markets disease overview and drug forecast to 2033.2024."},{"key":"e_1_2_9_5_1","volume-title":"Mounjaro\u00ae (Tirzepatide) injection [Package Insert]","author":"Eli Lilly and Company","year":"2022"},{"key":"e_1_2_9_6_1","volume-title":"Ozempic\u00ae (Semaglutide) injection [Package Insert]","author":"Novo Nordisk","year":"2023"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-023-01392-3"},{"key":"e_1_2_9_8_1","unstructured":"FDA.Drug\u2013Drug Interaction Assessment for Therapeutic Proteins | Guidance for Industry.2023https:\/\/www.fda.gov\/drugs\/guidance\u2010compliance\u2010regulatory\u2010information\/guidances\u2010drugsand\/or"},{"key":"e_1_2_9_9_1","volume-title":"Simcyp Simulator (Version 23) [Computer Software]","author":"Certara UK 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Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.70007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:13:42Z","timestamp":1761070422000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.70007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,23]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/phar.70007"],"URL":"https:\/\/doi.org\/10.1002\/phar.70007","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,23]]},"assertion":[{"value":"2024-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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