{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:34:58Z","timestamp":1791480898723,"version":"4.3.4"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100014941","name":"Cytokinetics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014941","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1007\/s40262-025-01481-9","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T23:06:24Z","timestamp":1738710384000},"page":"397-406","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of Aficamten"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9678-0133","authenticated-orcid":false,"given":"Donghong","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Lutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punag","family":"Divanji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youcef","family":"Benattia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2189-1474","authenticated-orcid":false,"given":"Stephen B.","family":"Heitner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5469-1287","authenticated-orcid":false,"given":"Stuart","family":"Kupfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"German","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"1481_CR1","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.jchf.2018.03.004","volume":"6","author":"BJ Maron","year":"2018","unstructured":"Maron BJ, Rowin EJ, Maron MS. Global burden of hypertrophic cardiomyopathy. JACC Heart Fail. 2018;6:376\u20138.","journal-title":"JACC Heart Fail."},{"key":"1481_CR2","doi-asserted-by":"publisher","first-page":"399","DOI":"10.2459\/JCM.0000000000001616","volume":"25","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Adamo M, Zou C, Porcari A, Tomasoni D, Rossi M, et al. Management of hypertrophic cardiomyopathy. J Cardiovasc Med (Hagerstown). 2024;25:399\u2013419.","journal-title":"J Cardiovasc Med (Hagerstown)"},{"key":"1481_CR3","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1136\/hrt.78.2.182","volume":"78","author":"S Cox","year":"1997","unstructured":"Cox S, O\u2019Donoghue AC, McKenna WJ, Steptoe A. Health related quality of life and psychological wellbeing in patients with hypertrophic cardiomyopathy. Heart. 1997;78:182\u20137.","journal-title":"Heart"},{"key":"1481_CR4","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.amjcard.2012.12.018","volume":"111","author":"E Reineck","year":"2013","unstructured":"Reineck E, Rolston B, Bragg-Gresham JL, Salberg L, Baty L, Kumar S, et al. Physical activity and other health behaviors in adults with hypertrophic cardiomyopathy. Am J Cardiol. 2013;111:1034\u20139.","journal-title":"Am J Cardiol"},{"key":"1481_CR5","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2016-000484","volume":"3","author":"J Sweeting","year":"2016","unstructured":"Sweeting J, Ingles J, Timperio A, Patterson J, Ball K, Semsarian C. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers. Open Heart. 2016;3: e000484.","journal-title":"Open Heart."},{"key":"1481_CR6","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jchf.2023.10.004","volume":"12","author":"CJ Coats","year":"2024","unstructured":"Coats CJ, Maron MS, Abraham TP, Olivotto I, Lee MMY, Arad M, et al. Exercise capacity in patients with obstructive hypertrophic cardiomyopathy: SEQUOIA-HCM baseline characteristics and study design. JACC Heart Fail. 2024;12:199\u2013215.","journal-title":"JACC Heart Fail."},{"key":"1481_CR7","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.jacc.2004.12.067","volume":"45","author":"C Autore","year":"2005","unstructured":"Autore C, Bernabo P, Barilla CS, Bruzzi P, Spirito P. The prognostic importance of left ventricular outflow obstruction in hypertrophic cardiomyopathy varies in relation to the severity of symptoms. J Am Coll Cardiol. 2005;45:1076\u201380.","journal-title":"J Am Coll Cardiol"},{"key":"1481_CR8","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/s41569-022-00682-0","volume":"19","author":"SJ Lehman","year":"2022","unstructured":"Lehman SJ, Crocini C, Leinwand LA. Targeting the sarcomere in inherited cardiomyopathies. Nat Rev Cardiol. 2022;19:353\u201363.","journal-title":"Nat Rev Cardiol"},{"key":"1481_CR9","doi-asserted-by":"publisher","first-page":"14142","DOI":"10.1021\/acs.jmedchem.1c01290","volume":"64","author":"C Chuang","year":"2021","unstructured":"Chuang C, Collibee S, Ashcraft L, Wang W, Vander Wal M, Wang X, et al. Discovery of aficamten (CK-274), a next-generation cardiac myosin inhibitor for the treatment of hypertrophic cardiomyopathy. J Med Chem. 2021;64:14142\u201352.","journal-title":"J Med Chem"},{"key":"1481_CR10","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.jacbts.2022.04.008","volume":"7","author":"FI Malik","year":"2022","unstructured":"Malik FI, Robertson LA, Armas DR, Robbie EP, Osmukhina A, Xu D, et al. A phase 1 dose-escalation study of the cardiac myosin inhibitor aficamten in healthy participants. JACC Basic Transl Sci. 2022;7:763\u201375.","journal-title":"JACC Basic Transl Sci."},{"key":"1481_CR11","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1056\/NEJMoa2401424","volume":"390","author":"MS Maron","year":"2024","unstructured":"Maron MS, Masri A, Nassif ME, Barriales-Villa R, Arad M, Cardim N, et al. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy. N Engl J Med. 2024;390:1849\u201361.","journal-title":"N Engl J Med"},{"key":"1481_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.70006","volume":"12","author":"D Xu","year":"2024","unstructured":"Xu D, Divanji P, Griffith A, Sukhun R, Cheplo K, Li J, et al. Pharmacokinetics, disposition, and biotransformation of the cardiac myosin inhibitor aficamten in humans. Pharmacol Res Perspect. 2024;12: e70006.","journal-title":"Pharmacol Res Perspect"},{"key":"1481_CR13","doi-asserted-by":"publisher","first-page":"1227470","DOI":"10.3389\/fphar.2023.1227470","volume":"14","author":"X Zhao","year":"2023","unstructured":"Zhao X, Liu H, Tian W, Fang L, Yu M, Wu X, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of aficamten in healthy Chinese participants: a randomized, double-blind, placebo-controlled, phase 1 study. Front Pharmacol. 2023;14:1227470.","journal-title":"Front Pharmacol"},{"key":"1481_CR14","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jacc.2022.10.020","volume":"81","author":"MS Maron","year":"2023","unstructured":"Maron MS, Masri A, Choudhury L, Olivotto I, Saberi S, Wang A, et al. Phase 2 study of aficamten in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2023;81:34\u201345.","journal-title":"J Am Coll Cardiol"},{"key":"1481_CR15","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/cts.13428","volume":"16","author":"P Ravenstijn","year":"2023","unstructured":"Ravenstijn P, Chetty M, Manchandani P, Elmeliegy M, Qosa H, Younis I. Design and conduct considerations for studies in patients with hepatic impairment. Clin Transl Sci. 2023;16:50\u201361.","journal-title":"Clin Transl Sci"},{"key":"1481_CR16","unstructured":"US Food and Drug Administration. Pharmacokinetics in patients with impaired hepatic function: Study design, data analysis, and impact on dosing and labeling. 2003 2018, Dec 24; Available from: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/pharmacokinetics-patients-impaired-hepatic-function-study-design-data-analysis-and-impact-dosing-and"},{"issue":"13","key":"1481_CR17","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.3390\/jcm11133898","volume":"11","author":"M Butzner","year":"2022","unstructured":"Butzner M, Rowin E, Yakubu A, Seale J, Robertson LA, Sarocco P, et al. Clinical characteristics and healthcare resource utilization among patients with obstructive hypertrophic cardiomyopathy treated in a range of settings in the United States. J Clin Med. 2022;11(13):3898.","journal-title":"J Clin Med"},{"key":"1481_CR18","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.amjcard.2022.03.023","volume":"174","author":"M Butzner","year":"2022","unstructured":"Butzner M, Sarocco P, Maron MS, Rowin E, Teng CC, Stanek E, et al. Characteristics of patients with obstructive hypertrophic cardiomyopathy in real-world community-based cardiovascular practices. Am J Cardiol. 2022;174:120\u20135.","journal-title":"Am J Cardiol"},{"key":"1481_CR19","doi-asserted-by":"publisher","first-page":"41","DOI":"10.5414\/CP202588","volume":"55","author":"K Shakeri-Nejad","year":"2017","unstructured":"Shakeri-Nejad K, Aslanis V, Veldandi UK, Gardin A, Zaehringer A, Dodman A, et al. Pharmacokinetics, safety, and tolerability of siponimod (BAF312) in subjects with different levels of hepatic impairment: a single-dose, open-label, parallel-group study. Int J Clin Pharmacol Ther. 2017;55:41\u201353.","journal-title":"Int J Clin Pharmacol Ther"},{"key":"1481_CR20","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1002\/cpdd.77","volume":"3","author":"X Chen","year":"2014","unstructured":"Chen X, Shi JG, Emm T, Scherle PA, McGee RF, Lo Y, et al. Pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 phosphate) in renal and hepatic impairment patients. Clin Pharmacol Drug Dev. 2014;3:34\u201342.","journal-title":"Clin Pharmacol Drug Dev."},{"key":"1481_CR21","doi-asserted-by":"publisher","first-page":"S327","DOI":"10.14309\/01.ajg.0000776412.04273.9e","volume":"116","author":"C Lee","year":"2021","unstructured":"Lee C, Tang Y, Schroeder C, Zhang J, Nguyen-Cleary T, Ma M, et al. Pharmacokinetics (PK), safety, and tolerability of etrasimod (APD334) in participants with mild, moderate, or severe hepatic impairment: a single-dose, open-label, Parallel-Group Study. Am J Gastroenterol. 2021;116:S327\u20138.","journal-title":"Am J Gastroenterol"},{"key":"1481_CR22","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1007\/s40262-023-01261-3","volume":"62","author":"U Duthaler","year":"2023","unstructured":"Duthaler U, Bachmann F, Ozbey AC, Umehara K, Parrott N, Fowler S, et al. The activity of members of the UDP-glucuronosyltransferase subfamilies UGT1A and UGT2B is impaired in patients with liver cirrhosis. Clin Pharmacokinet. 2023;62:1141\u201355.","journal-title":"Clin Pharmacokinet"}],"updated-by":[{"DOI":"10.1007\/s40262-025-01557-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000}}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01481-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-025-01481-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01481-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T05:02:47Z","timestamp":1757134967000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-025-01481-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["1481"],"URL":"https:\/\/doi.org\/10.1007\/s40262-025-01481-9","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s40262-025-01557-6","asserted-by":"object"}]},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"assertion":[{"value":"15 January 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2025","order":3,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":4,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised to correct the term SEQUOIA throughout the article.","order":5,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2025","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s40262-025-01557-6","URL":"https:\/\/doi.org\/10.1007\/s40262-025-01557-6","order":9,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All study protocols were reviewed by site-specific institutional review boards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"All participants provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"This study was funded by Cytokinetics, Incorporated.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All authors participated in the conception and planning of the study; Donghong Xu, Justin Lutz, Punag Divanji, Youcef Benattia, Adrienne Griffith and Polina German participated in the design of the study. Donghong Xu, Justin Lutz and Polina German participated in the acquisition, analysis, and interpretation of data. All authors critically revised and approved the final version of the manuscript.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}},{"value":"Donghong Xu, Justin D. Lutz, Punag Divanji, Adrienne Griffith, Stephen B. Heitner, Stuart Kupfer, and Polina German: Employees of and hold stock in Cytokinetics, Incorporated. Youcef Benattia, and Jianlin Li: Paid consultant for Cytokinetics, Incorporated.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials and can also be obtained from the corresponding author upon reasonable request.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}}]}}