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Initial in\u00a0vitro studies indicated that temsavir, the active moiety of fostemsavir, and its metabolites, inhibited organic cation transporter (OCT)1, OCT2, and multidrug and toxin extrusion transporters (MATEs) at tested concentration of 100 uM, although risk assessment based on the current Food and Drug <jats:italic>Administration<\/jats:italic> in\u00a0vitro drug\u2013drug interaction (DDI) guidance using the mechanistic static model did not reveal any clinically relevant inhibition on OCTs and MATEs. However, a DDI risk was flagged with EMA static model predictions. Hence, a physiologically based pharmacokinetic (PBPK) model of fostemsavir\/temsavir was developed to further assess the DDI risk potential of OCT and MATEs inhibition by temsavir and predict changes in metformin (a sensitive OCT and MATEs substrate) exposure. No clinically relevant impact on metformin concentrations across a wide range of temsavir concentrations was predicted; therefore, no dose adjustment is recommended for metformin when co\u2010administered with fostemsavir.<\/jats:p>","DOI":"10.1002\/prp2.1238","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T06:04:00Z","timestamp":1720677840000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["No dose adjustment of metformin or substrates of organic cation transporters (<scp>OCT<\/scp>)1 and <scp>OCT2<\/scp> and multidrug and toxin extrusion protein (<scp>MATE<\/scp>)1\/<scp>2K<\/scp> with fostemsavir coadministration based on modeling approaches"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7168-3234","authenticated-orcid":false,"given":"Dung","family":"Nguyen","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville 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