{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T18:20:24Z","timestamp":1770574824692,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Momelotinib\u2014approved for treatment of myelofibrosis in adults with anemia\u2014and its major active metabolite, M21, were assessed as drug\u2013drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple\u2010dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1\/1B3 inhibitor (single\u2010dose rifampin), and a strong CYP3A4 inducer (multiple\u2010dose rifampin). Momelotinib DDI perpetrator potential (multiple\u2010dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively). DDI was assessed from changes in maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), area under the concentration\u2013time curve (AUC), time to reach <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, and half\u2010life. The increase in momelotinib (23% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 14% AUC) or M21 (30% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 24% AUC) exposure with ritonavir coadministration was not clinically relevant. A moderate increase in momelotinib (40% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 57% AUC) and minimal change in M21 was observed with single\u2010dose rifampin. A moderate decrease in momelotinib (29% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 46% AUC) and increase in M21 (31% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 15% AUC) were observed with multiple\u2010dose rifampin compared with single\u2010dose rifampin. Due to potentially counteracting effects of OATP1B1\/1B3 inhibition and CYP3A4 induction, multiple\u2010dose rifampin did not significantly change momelotinib pharmacokinetics compared with momelotinib alone (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> no change, 15% AUC decrease). Momelotinib did not alter the pharmacokinetics of midazolam (8% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 16% AUC decreases) or 1\u2032\u2010hydroxymidazolam (14% <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 16% AUC decreases) but increased rosuvastatin <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> by 220% and AUC by 170%. Safety findings were mild in this short\u2010term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1\/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments.<\/jats:p>","DOI":"10.1111\/cts.13799","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T10:10:11Z","timestamp":1713435011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical assessment of momelotinib drug\u2013drug interactions via <scp>CYP3A<\/scp> metabolism and transporters"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0074-1938","authenticated-orcid":false,"given":"Yu Liu","family":"Ho","sequence":"first","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6366-7310","authenticated-orcid":false,"given":"Pete","family":"Gorycki","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5703-8315","authenticated-orcid":false,"given":"Geraldine","family":"Ferron\u2010Brady","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2598-4520","authenticated-orcid":false,"given":"Paul","family":"Martin","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-9712","authenticated-orcid":false,"given":"Georgios","family":"Vlasakakis","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Prescribing Information","author":"Ojjaara (momelotinib)","year":"2023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-740092"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002662"},{"key":"e_1_2_10_5_1","unstructured":"European Commission authorises GSK's Omjjara (momelotinib). 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