{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T16:42:04Z","timestamp":1725036124909},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"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":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abrocitinib is a selective Janus kinase 1 inhibitor for the treatment of moderate to severe atopic dermatitis (AD). To assess the relationship between abrocitinib plasma concentrations and heart rate (HR)\u2013corrected QT (QTc) and HR and calculate the effect of abrocitinib on these parameters at supratherapeutic concentrations, 36 healthy volunteers received single doses of abrocitinib 600 mg, placebo, and moxifloxacin 400 mg in a 3\u2010period crossover study. The relationship between change from baseline in Fridericia\u2010corrected QTc (\u2206QTcF) values and abrocitinib plasma concentrations was modeled using a prespecified linear mixed\u2010effects model. The 90%CIs for time\u2010matched placebo\u2010corrected \u2206QTcF (\u2206\u2206QTcF) were calculated from model parameter estimates and assessed against the regulatory threshold (10 millisecond) at the predicted supratherapeutic concentration in patients with atopic dermatitis (2156 ng\/mL). Mean (90%CI) time\u2010matched placebo\u2010corrected change from baseline in HR (\u2206\u2206HR) was calculated similarly. At the supratherapeutic concentration, mean (90%CI) estimates for \u2206\u2206QTcF and \u2206\u2206HR were 6.00 (4.52\u20107.49) milliseconds and 6.51 (5.23\u20107.80) bpm, respectively. Despite a concentration\u2010dependent effect on \u2206QTcF and \u2206HR, with statistically significant slopes (90%CI) of 0.0026 (0.0018\u20100.0035) milliseconds\/(ng\/mL) and 0.0031 (0.0024\u20100.0038) bpm\/(ng\/mL), respectively, abrocitinib does not have a clinically significant effect on QTc interval or HR at supratherapeutic exposures.<\/jats:p>","DOI":"10.1002\/cpdd.1111","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T15:14:53Z","timestamp":1652109293000},"page":"1036-1045","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population Pharmacokinetic\/Pharmacodynamic Modeling of the Effect of Abrocitinib on QT Intervals in Healthy Volunteers"],"prefix":"10.1002","volume":"11","author":[{"given":"Xiaoxing","family":"Wang","sequence":"first","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaj","family":"Gupta","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bimal K.","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saleem Ashley","family":"Farooqui","sequence":"additional","affiliation":[{"name":"Pfizer R &amp; D UK Ltd.  Sandwich Kent UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu H.","family":"Le","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Wojciechowski","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  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