{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:59:46Z","timestamp":1791597586144,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016619","name":"MyoKardia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001009","name":"Bristol Myers Squibb Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single\u2010center, open\u2010label study in healthy participants. Participants received: on day 1, midazolam 5 mg; on days 2\u20103, mavacamten 25\u00a0mg; on days 4\u201016, mavacamten 15 mg; and on day 17, mavacamten 15 mg and midazolam 5 mg. Plasma concentrations of mavacamten, midazolam, and the midazolam metabolite 1\u2032\u2010hydroxymidazolam were measured. A physiologically based pharmacokinetic (PBPK) model was used to simulate the effect of mavacamten\u2010mediated CYP3A4 induction on midazolam exposure by CYP2C19 phenotype. Thirteen adult participants were enrolled (46.2% were female; mean [SD] age: 34.0 [9.0] years). Compared with midazolam alone, midazolam coadministered with mavacamten decreased the maximum observed plasma concentration (C<jats:sub>max<\/jats:sub>), area under the drug concentration\u2010time curve (AUC) from time zero to infinity (AUC<jats:sub>0\u2010inf<\/jats:sub>), and AUC from time zero to last measurable concentration (AUC<jats:sub>0\u2010last<\/jats:sub>) for midazolam by 7%, 13%, and 24%, respectively; for 1\u2032\u2010hydroxymidazolam, AUC<jats:sub>0\u2010inf<\/jats:sub> and AUC<jats:sub>0\u0200last<\/jats:sub> increased by 20% and 11%, respectively. Ten participants experienced adverse events and the majority were mild in severity. The PBPK model predicted the clinical trial data well. The PBPK simulation assessed that the overall impact of mavacamten on midazolam C<jats:sub>max<\/jats:sub> and AUC was predicted to be weak regardless of CYP2C19 phenotype. At clinically relevant exposures, mavacamten had a negligible effect on midazolam exposure.<\/jats:p>","DOI":"10.1002\/jcph.6175","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T11:03:29Z","timestamp":1734519809000},"page":"598-606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Drug\u2013Drug Interaction Potential of Mavacamten with Midazolam: Combined Results from Clinical and Model\u2010Based Studies"],"prefix":"10.1002","volume":"65","author":[{"given":"Samira","family":"Merali","sequence":"first","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sychterz","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidya","family":"Perera","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Gaohua","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Florea","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bindu","family":"Murthy","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.02.014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad194"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.644682"},{"key":"e_1_2_10_5_1","unstructured":"CAMZYOS (mavacamten).USprescribing information.2024. 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