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This analysis aimed to add to the pharmacokinetic knowledge of the medication, through development of a population pharmacokinetic model and identification of factors that affect drug disposition. Plasma samples from 5 clinical trials were collated, composed of healthy volunteers, patients with psoriasis and patients with alopecia areata taking oral brepocitinib. NONMEM was used to develop a population pharmacokinetic model, and patient demographics were tested as covariates. The final model was a 1\u2010compartment model with first\u2010order absorption. The typical values for apparent clearance and apparent volume of distribution were 18.7 L\/h (78% coefficient of variation [CV]) and 136 L (60.5% CV), respectively. Absorption was rapid with an absorption constant of 3.46 h, with an absorption lag of 0.24 hours observed with the oral tablet formulation. The proportional residual error was found to be 52.7% CV in healthy volunteers and 87.5% CV in patients. High\u2010fat meals were associated with a reduction in both the rate (69.9% lower) and extent (28.3% lower) of absorption, while Asian populations had reduced clearance (24.3% lower). Nonlinear pharmacokinetics were observed at doses of 175 mg and above, with a 35.1% higher relative bioavailability at these doses. There were insufficient data to describe this nonlinearity as a continuous relationship. This initial description of the population pharmacokinetics will act as a foundation for the model\u2010informed drug development of brepocitinib and will facilitate future modeling of this medicine. ClinicalTrials.gov numbers NCT02310750 NCT03236493 NCT03656952 NCT02969018 NCT02974868.<\/jats:p>","DOI":"10.1002\/cpdd.1163","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T04:45:06Z","timestamp":1662007506000},"page":"1447-1456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients"],"prefix":"10.1002","volume":"11","author":[{"given":"Jim H.","family":"Hughes","sequence":"first","affiliation":[{"name":"Pfizer Global Research and Development  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruolun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Banfield","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin E.","family":"Dowty","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development  Groton Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00917"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01261-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.11.025"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3661"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.11.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1046"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.03.962"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.03.050"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.11.027"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12049"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12611"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199630050-00001"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-3-319-19425-7_4","volume-title":"Multivariable Modeling Strategies. 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