{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T19:25:57Z","timestamp":1780428357611,"version":"3.54.1"},"reference-count":19,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The neurokinin 3 receptor antagonist fezolinetant is an approved treatment for vasomotor symptoms due to menopause. The impacts of hepatic and renal impairment on the pharmacokinetics and safety of a single oral dose of fezolinetant 30 mg were investigated in two independent studies. The studies enrolled healthy women and women with mild or moderate hepatic impairment (defined by Child\u2013Pugh classification) or mild to severe renal impairment (categorized by estimated glomerular filtration rate). Blood samples for fezolinetant and its metabolite, ES259564, were collected predose and up to 96 h postdose. Safety was assessed using treatment\u2010emergent adverse events (TEAEs). Overall, 26 and 27 women were enrolled in the hepatic and renal studies. Fezolinetant exposure (area under the concentration\u2013time curve from time of dosing to infinity [AUC\n                    <jats:sub>inf<\/jats:sub>\n                    ]) was higher in those with hepatic impairment than women with normal function (geometric mean ratios [90% confidence interval]: mild\/healthy control: 155.89% [108.04%\u2010224.92%], moderate\/healthy control: 196.11% [131.64%\u2010292.15%]). The AUC\n                    <jats:sub>inf<\/jats:sub>\n                    results for ES259564 were similar between women who were hepatically impaired and of normal functioning. Renal impairment did not substantially increase the exposure of fezolinetant. However, those with moderate or severe renal impairment had higher AUC\n                    <jats:sub>last<\/jats:sub>\n                    (from time of dosing to last measurable concentration) results for ES259564 than healthy women (moderate\/healthy control: 177.14 [120.02\u2010261.44], severe\/healthy control: 478.56 [347.93\u2010658.22]). No serious TEAEs were reported in either study. In conclusion, hepatic impairment affects the metabolism of fezolinetant as shown by progressive increases in systemic exposure. Marginal impacts were noted in women with renal impairment.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70070","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T04:09:18Z","timestamp":1752206958000},"page":"1517-1530","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics and Safety of Fezolinetant in Women with Hepatic or Renal Impairment"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4323-8266","authenticated-orcid":false,"given":"Megumi","family":"Iwai","sequence":"first","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-0762","authenticated-orcid":false,"given":"Xuegong","family":"Wang","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4921-1535","authenticated-orcid":false,"given":"Melanie","family":"Patton","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4718-8023","authenticated-orcid":false,"given":"Lauren","family":"Benner","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakyo","family":"Heo","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4950-7957","authenticated-orcid":false,"given":"Jace C.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8221-2894","authenticated-orcid":false,"given":"Anna","family":"Spence","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6416-3314","authenticated-orcid":false,"given":"Thomas C.","family":"Marbury","sequence":"additional","affiliation":[{"name":"Orlando Clinical Research Center  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Huang","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.  Northbrook IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogc.2011.05.006"},{"key":"e_1_2_11_3_1","unstructured":"US Food and Drug Administration.Veozah (fezolinetant) prescribing information.2023. Last update: December 2024. Accessed March 24 2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/216578s004lbl.pdf"},{"key":"e_1_2_11_4_1","unstructured":"European Medicines Agency.Veoza (fezolinetant) summary of product characteristics.2023. Last update: March 21 2025. Accessed March 24 2025.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/veoza\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_11_5_1","unstructured":"Medicines and Healthcare Products Regulatory Agency.Public assessment report: Veoza 45 mg film\u2010coated tablets (fezolinetant).2024. Last update: March 14 2025. Accessed March 24 2025.https:\/\/mhraproducts4853.blob.core.windows.net\/docs\/452eebb63cf697a3a4bea8b85ed6effbfa0f7332"},{"key":"e_1_2_11_6_1","unstructured":"VEOZATM (FEZOLINETANT).Public Risk Management Plan (RMP) summary. December 12 2023. Accessed March 5 2025 https:\/\/www.swissmedic.ch\/dam\/swissmedic\/en\/dokumente\/marktueberwachung\/rmp\/fezolinetant_veoza_rmp\u2010summary.pdf.download.pdf\/Fezolinetant_Veoza_Public_Risk_Management_Plan_Summary.pdf"},{"key":"e_1_2_11_7_1","unstructured":"Astellas Pharma (Thailand) Co Ltd.Veoza (fezolinetant) package insert.2024. Last update: January 2025. Accessed March 24 2025 https:\/\/ndi.fda.moph.go.th\/uploads\/drug_detail_corporation\/doc\/word\/1263\/7c4b97727e0e458e6b8908689db94332\u2010a1.pdf"},{"key":"e_1_2_11_8_1","unstructured":"Astellas Pharma Australia Pty Ltd.Australian product information Veoza (fezolinetant).2024. Last update: July 16 2024. Accessed March 24 2025.https:\/\/www.ebs.tga.gov.au\/ebs\/picmi\/picmirepository.nsf\/pdf?OpenAgent=&id=CP-2024-PI-01388-1&d=20240314172310101&d=20241004172310101"},{"key":"e_1_2_11_9_1","unstructured":"Astellas Pharma Canada.Veozah (fezolinetant) product monograph: including patient medication information.2024. Last update: December 2 2024. Accessed March 24 2025.https:\/\/pdf.hres.ca\/dpd_pm\/00077931.PDF"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2021.1893305"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad058"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)00085\u20105"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.6157"},{"key":"e_1_2_11_14_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER).Nonclinical reviews. Fezolinetant (or ESN 364) for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause (NDA 216578).2023. Last update: May 2 2023. Accessed April 30 2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2023\/216578Orig1s000PharmR.pdf"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.08042fp"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706138"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050394"},{"key":"e_1_2_11_18_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER).Pharmacokinetics in patients with impaired renal function \u2013 study design data analysis and impact on dosing. Guidance for industry.2024. Last update: March 2024. Accessed April 30 2025.https:\/\/www.fda.gov\/media\/78573\/download"},{"key":"e_1_2_11_19_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER).Guidance for industry. Pharmacokinetics in patients with impaired hepatic function: study design data analysis and impact on dosing and labeling.2003. Last update: May 2003. Accessed April 30 2025.https:\/\/www.fda.gov\/media\/71311\/download."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.05.006"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T07:43:48Z","timestamp":1761983028000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jcph.70070"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70070","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]},"assertion":[{"value":"2025-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}