{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T11:39:53Z","timestamp":1792237193227,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Daprodustat, an oral hypoxia\u2010inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2\u2010period, crossover study in 6 healthy men characterized the absorption, distribution, and excretion of daprodustat when administered as oral and intravenous (IV) doses of unlabeled and radiolabeled daprodustat ([<jats:sup>14<\/jats:sup>C]\u2010GSK1278863). Tolerability and pharmacokinetic properties of daprodustat, and its 6 metabolites in the systemic circulation, were also evaluated. The mean recovery of radiolabeled daprodustat was \u224895% by day 5, with the majority in feces and minor renal elimination, indicating that daprodustat and metabolites are primarily eliminated via hepatobiliary and fecal routes. Approximately 40% of total circulating radioactivity in plasma following both IV and oral administration was daprodustat; thus, 60% was attributed to metabolites. It was estimated that \u224880% of daprodustat was absorbed across the gastrointestinal tract, and \u224818% cleared by hepatic extraction. Pharmacokinetics were essentially dose proportional, with moderate (\u224866%) oral tablet bioavailability. Following IV administration, daprodustat plasma clearance (19.3 L\/h) and volume of distribution (14.6 L) were low, suggesting low tissue distribution outside systemic circulation with likely low penetration into tissues. Daprodustat was generally well tolerated, with no deaths or serious or significant adverse events reported.<\/jats:p>","DOI":"10.1002\/cpdd.1029","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T06:16:03Z","timestamp":1635488163000},"page":"1419-1431","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Clinical Pharmacokinetics of Daprodustat: Results of an Absorption, Distribution, and Excretion Study With Intravenous Microtracer and Concomitant Oral Doses for Bioavailability Determination"],"prefix":"10.1002","volume":"10","author":[{"given":"Kelly M.","family":"Mahar","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modeling &amp; Simulation GlaxoSmithKline  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Caltabiano","sequence":"additional","affiliation":[{"name":"Development\u2010Clinical 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