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Blood samples from phase I HV and phase II clinical studies of patients with alopecia areata, psoriasis, psoriatic arthritis, ulcerative colitis (UC), vitiligo, and hidradenitis suppurativa were analyzed using a nonlinear mixed\u2010effects modeling approach. Effects of patients' characteristics on brepocitinib exposure were investigated. Overall, 8552 brepocitinib plasma concentrations from 775 individuals were included in the analysis. The PKs of brepocitinib were adequately described by a two\u2010compartment model with first\u2010order absorption and a lag time for tablet formulation, dose\u2010dependent bioavailability, and Box\u2013Cox transformed interindividual variabilities on apparent clearance (CL\/F) and apparent central volume of distribution (Vc\/F). For a typical 70\u2010kg non\u2010Asian female patient with baseline aspartate aminotransferase of 22 unit\/liter, CL\/F and Vc\/F estimates were 17.5 L\/h and 88.5 L, respectively. Asians had a higher exposure (independent of body weight), caused by a 10% lower CL\/F when compared to other individuals. Independent of baseline body weight, the male population showed 13% higher Vc\/F compared to the female population. Patients with UC were predicted to have 46% slower absorption rate compared to other individuals. The PKs of brepocitinib were well\u2010characterized by a two\u2010compartment model with first\u2010order absorption and dose\u2010dependent bioavailability. Several covariates, such as race and sex, were identified to have statistically significant, but not clinically meaningful, effects on the estimated PK parameters.<\/jats:p>","DOI":"10.1002\/psp4.13100","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T06:07:11Z","timestamp":1707458831000},"page":"551-562","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population pharmacokinetic modeling of oral brepocitinib in healthy volunteers and patients with immuno\u2010inflammatory diseases"],"prefix":"10.1002","volume":"13","author":[{"given":"Farzaneh","family":"Maleki","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Bioanalytics, Worldwide Research, Development and Medical Pfizer Inc.  Cambridge Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8860-0576","authenticated-orcid":false,"given":"Elias","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Mathematics University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-5792","authenticated-orcid":false,"given":"Christopher","family":"Banfield","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Bioanalytics, Worldwide Research, Development and Medical Pfizer Inc.  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