{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T13:19:04Z","timestamp":1778332744550,"version":"3.51.4"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>Obeldesivir is an oral nucleoside analog prodrug inhibitor of SARS\u2010CoV\u20102 RNA\u2010dependent RNA polymerase and other viral polymerases. Here, two Phase I studies evaluated potential drug\u2013drug interactions between obeldesivir and substrates or inhibitors of cytochrome P450 and drug transporters in healthy participants. When obeldesivir was tested as a precipitant, pharmacokinetic parameter point estimates for midazolam (CYP3A4 inhibition\/induction), caffeine (CYP1A2 inhibition), and metformin (organic cation transporter 1 inhibition) exposures were within 80\u2013125% no\u2010effect bounds representing the interval within which a systemic exposure change does not warrant clinical action based on EMA\/FDA guidance. Dabigatran (P\u2010glycoprotein substrate) and pitavastatin (organic anion transporting polypeptide 1B1\/1B3 substrate) exposures decreased by approximately 25% and 30%, respectively, with obeldesivir coadministration; these were considered not clinically relevant, as these exposure changes are not associated with dose changes or precautions in the US prescribing information for these drugs. When obeldesivir was evaluated as an object, exposures of GS\u2010441524, the parent nucleoside metabolite of obeldesivir, were within the 80\u2013125% no\u2010effect bounds for ritonavir (P\u2010glycoprotein inhibition) and cyclosporin A (breast cancer resistance protein inhibition) coadministration [Correction added on 7 February 2025, after first online publication: The word monophosphate has been removed in this version.]. Famotidine (gastric acid suppression) coadministration decreased GS\u2010441524 exposure by approximately 26%; this was within the range of exposures observed in previous Phase III studies and was considered not clinically relevant. Obeldesivir was well tolerated, and adverse events were mild to moderate. These findings indicate that obeldesivir has low potential for drug\u2013drug interactions. Obeldesivir remains a promising treatment against a broad spectrum of viruses given its antiviral activity and favorable safety profile.<\/jats:p>","DOI":"10.1002\/cpt.3575","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T13:29:22Z","timestamp":1738330162000},"page":"1403-1412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Evaluation of Drug\u2013Drug Interactions with Obeldesivir, an Orally Administered Antiviral Agent"],"prefix":"10.1002","volume":"117","author":[{"given":"Chi\u2010Chi","family":"Peng","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc.  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1573-793X","authenticated-orcid":false,"given":"Rita","family":"Humeniuk","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.  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