{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:50:46Z","timestamp":1760986246628,"version":"3.40.5"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>We report on investigations exploring the P2X3\u2010receptor antagonist filapixant's effect on taste perception and cough\u2010reflex sensitivity and describe its pharmacokinetics, including its CYP3A4\u2010interaction potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a randomized, placebo\u2010controlled, double\u2010blind study, 3\u2009\u00d7\u200912 healthy men (18\u201045\u2009years) were assigned (3:1) to filapixant (20, 80 or 250\u2009mg by mouth) or placebo twice daily over 2\u00a0weeks. A single dose of midazolam (1\u00a0mg), a CYP3A4 substrate, was administered with and without filapixant. Assessments included a taste\u2010strips test, a taste questionnaire, cough challenge with adenosine triphosphate, adverse event reports and standard safety assessments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Taste disturbances were observed mainly in the 250\u2010mg group: six of nine participants (67%) in this group reported hypo\u2010 or dysgeusia in the questionnaire; eight participants (89%) reported taste\u2010related adverse events. Five participants (56%) had a decrease in overall taste\u2010strips\u2010test scores \u22652 points (point estimate \u22121.1 points, 90% confidence interval [\u22123.3; 1.1]). Cough counts increased with adenosine triphosphate concentration but without major differences between treatments. Filapixant exposure increased proportionally to dose. Co\u2010administration of filapixant had no clinically relevant effect on midazolam pharmacokinetics. Area under the concentration\u2010time curve ratios and 90% confidence intervals were within 80\u2010125%. No serious or severe adverse events were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, filapixant was safe and well tolerated, apart from mild, transient taste disturbances. Such disturbances occurred more frequently than expected based on (in vitro) receptor\u2010selectivity data, suggesting that other factors than P2X3:P2X2\/3 selectivity might also play an important role in this context. The cough\u2010challenge test showed no clear treatment effect. Filapixant has no clinically relevant CYP3A4 interaction potential.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16091","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T08:20:03Z","timestamp":1716366003000},"page":"2004-2018","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacodynamics, pharmacokinetics and CYP3A4 interaction potential of the selective P2X3 receptor antagonist filapixant: A randomized multiple ascending\u2010dose study in healthy young men"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-4808","authenticated-orcid":false,"given":"Christian","family":"Friedrich","sequence":"first","affiliation":[{"name":"Bayer AG  Berlin Germany"},{"name":"Brandenburg Medical School Theodor Fontane Faculty of Health Sciences Brandenburg  Brandenburg an der Havel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-7075","authenticated-orcid":false,"given":"Dave","family":"Singh","sequence":"additional","affiliation":[{"name":"Medicines Evaluation Unit Division of Infection, Immunity &amp; 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