{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:55Z","timestamp":1786977955590,"version":"build-2736575974"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gefapixant (MK\u20107264, RO4926219, AF\u2010219) is a first\u2010in\u2010class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single\u2010 and multiple\u2010dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single\u2010dose administration of 10\u2010450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter\u2010subject variability and a dose\u2010proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose\u2010proportional at doses ranging from 7.5 to 50 mg and less than dose\u2010proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post\u2010dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half\u2010life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single\u2010dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice\u2010daily dosing regimen.<\/jats:p>","DOI":"10.1002\/jcph.2442","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T03:44:15Z","timestamp":1713843855000},"page":"1023-1029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Single\u2010 and Multiple\u2010Dose Pharmacokinetics of Gefapixant (MK\u20107264), a P2X3 Receptor Antagonist, in Healthy Adults"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-7041","authenticated-orcid":false,"given":"Jesse C.","family":"Nussbaum","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc.  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