{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:59:46Z","timestamp":1792879186455,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bemnifosbuvir is a novel oral guanosine nucleotide prodrug candidate for the treatment of chronic hepatitis C virus infection. Potential drug\u2013drug interactions (DDIs) of bemnifosbuvir as a substrate or perpetrator with regard to ATP\u2010binding cassette (ABC) and solute carrier (SLC) transporters were evaluated in vitro and in clinical studies. Bemnifosbuvir was demonstrated in vitro as a substrate and inhibitor of the ABC transporters\u2019 P\u2010glycoprotein (P\u2010gp), as an inhibitor of the breast cancer resistance protein (BCRP), as well as a weak inhibitor of SLC transporters, including organic anion transporting polypeptide 1B1 (OATP1B1). Phase 1 studies in healthy participants were subsequently conducted to assess the clinical significance of transporter\u2010mediated DDI potentials of bemnifosbuvir as a precipitant using digoxin and rosuvastatin as P\u2010gp and BCRP\/OATP1B1 index substrates, respectively. A single dose of 0.25 mg digoxin or 10 mg rosuvastatin was administered alone and with 1100 mg bemnifosbuvir, either simultaneously or staggered. Simultaneous administration of a single dose of 1100 mg bemnifosbuvir increased total plasma exposure of both drugs by less than 20%, and transiently increased the peak plasma exposure of digoxin and rosuvastatin by 78% and 40%, respectively. Staggered dosing reduced the magnitude of changes in peak exposure to digoxin and rosuvastatin. No serious adverse events or drug discontinuations were observed. Dose adjustments are therefore unlikely for drugs that are substrates of P\u2010gp or BCRP\/OAT1B1 when coadministered with bemnifosbuvir, and staggered dosing may further reduce any DDI risk.<\/jats:p>","DOI":"10.1002\/jcph.70114","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T16:25:42Z","timestamp":1758990342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro and Clinical Evaluation of Potential Interactions of Bemnifosbuvir with Drug Transporters"],"prefix":"10.1002","volume":"66","author":[{"given":"Xiao\u2010Jian","family":"Zhou","sequence":"first","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Vo","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Morelli","sequence":"additional","affiliation":[{"name":"Altasciences Company, Inc.  Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Montrond","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannan","family":"Lynch","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Belanger","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Horga","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Hammond","sequence":"additional","affiliation":[{"name":"Atea Pharmaceuticals, Inc.  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02479-20"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227104"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01201-19"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/fvl-2023-0115"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28113-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2305137"},{"key":"e_1_2_10_8_1","unstructured":"ZhouXJ BerlibaE JucovA et\u00a0al.HCV viral kinetic analysis predicts shorter treatment duration with AT\u2010527 a purine nucleotide prodrug with potent pan\u2010genotypic antiviral activity in HCV\u2010infected subjects regardless of cirrhosis status. Abstract and poster number 1640. Presented at:The Liver Meeting; November 8\u201312 2019;Boston MA."},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(20)31210-1"},{"key":"e_1_2_10_10_1","unstructured":"GoodSS LinK LuoS VoA AgrawalN SommadossiJP.The combination of bemnifosbuvir (BEM) and ruzasvir (RZR) the HCV NS5B and NS5A inhibitors demonstrates potent in vitro synergistic antiviral activity and in vivo preclinical safety without adverse interactions. Abstract and poster number 411. Presented at:36th International Conference on Antiviral Research (ICAR);2023;Lyon France."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1540"},{"key":"e_1_2_10_12_1","unstructured":"ZhouXJ MorelliG MontrondM et\u00a0al. Lack of pharmacokinetic drug\u2013drug interaction between bemnifosbuvir and ruzasvir in healthy participants. Abstract and poster number 1879\u2010A. Presented at: American Association for the Study of Liver Diseases (AASLD); November 10\u201314 2023;Boston MA."},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","unstructured":"JucovA HamidS IliescuL et\u00a0al.Efficacy and safety of bemnifosbuvir and ruzasvir after 8 weeks of treatment in patients with chronic hepatitis C virus (HCV) infection.Abstract and poster number TOP\u2010251. Presented at: The European Association for the Study of the Liver (EASL) Congress; May 7\u201310 2025;Amsterdam The Netherlands.","DOI":"10.1016\/S0168-8278(25)02179-8"},{"issue":"7","key":"e_1_2_10_14_1","first-page":"601","article-title":"Pharmacokinetic drug\u2010drug interaction and their implication in clinical management","volume":"18","author":"Palleria C","year":"2013","journal-title":"J Res Med Sci"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3028"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11020075"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2670"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-009-9924-0"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4315-6"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24848"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-018-3148-z"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15091126"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.04.016"},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","unstructured":"ZhouXJ MorelliG LafranceJP et\u00a0al.Pharmacokinetics of Bemnifosbuvir in Participants With Renal Impairment. Abstract and poster number WED\u2010280. Presented at: The European Association for the Study of the Liver (EASL) Congress; May 7\u201310 2025;Amsterdam The Netherlands.","DOI":"10.1016\/S0168-8278(25)02192-0"},{"key":"e_1_2_10_25_1","unstructured":"US Food and Drug Administration (FDA).CRESTOR\u00ae(rosuvastatin). Prescribing information. AstraZeneca. Accessed September 2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/021366s046lbl.pdf"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.377"},{"key":"e_1_2_10_27_1","unstructured":"US Food and Drug Administration (FDA).Draft Guidance on Digoxin. 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