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Data were pooled from phase I (NCT01513902), phase III (NCT02592434), and open\u2010label, long\u2010term extension (NCT01500551) studies of tofacitinib tablet\/solution (weight\u2010based doses administered twice daily [b.i.d.]) in patients with JIA aged 2 to less than 18\u2009years. Population PK modeling used a nonlinear mixed\u2010effects approach, with covariates identified using stepwise forward\u2010inclusion backward\u2010deletion procedures. Simulations were performed to derive dosing recommendations for children and adolescents with JIA. Two hundred forty\u2010six pediatric patients were included in the population PK model. A one\u2010compartment model with first\u2010order elimination and absorption with body weight as a covariate for oral clearance and apparent volume of distribution sufficiently described the data. Oral solution was associated with comparable average concentration (<jats:italic>C<\/jats:italic><jats:sub>avg<\/jats:sub>) and slightly higher (113.9%) maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) versus tablet, which was confirmed by a subsequent randomized, open\u2010label, bioavailability study conducted in healthy adult participants (<jats:italic>n<\/jats:italic>\u2009=\u200912) by demonstrating adjusted geometric mean ratios (90% confidence interval) between oral solution and tablet of 1.04 (1.00\u20131.09) and 1.10 (1.00\u20131.21) for area under the curve extrapolated to infinity and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, respectively (NCT04111614). A dosing regimen of 3.2\u2009mg b.i.d. solution in patients 10 to less than 20\u2009kg, 4\u2009mg b.i.d. solution in patients 20 to less than 40\u2009kg, and 5\u2009mg b.i.d. tablet\/solution in patients greater than or equal to 40\u2009kg, irrespective of age, was proposed to achieve constant <jats:italic>C<\/jats:italic><jats:sub>avg<\/jats:sub> across weight groups. In summary, population PK characterization informed a simplified tofacitinib dosing regimen that has been implemented in pediatric patients with JIA.<\/jats:p>","DOI":"10.1002\/psp4.13104","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T07:54:55Z","timestamp":1706774095000},"page":"599-611","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tofacitinib pharmacokinetics in children and adolescents with juvenile idiopathic arthritis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-9921","authenticated-orcid":false,"given":"Cheng","family":"Chang","sequence":"first","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9390-2710","authenticated-orcid":false,"given":"Camille","family":"Vong","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-8667","authenticated-orcid":false,"given":"Xiaoxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anasuya","family":"Hazra","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Diehl","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"1991","article-title":"Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997","volume":"25","author":"Petty RE","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_11_3_1","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty RE","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201388"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.180168"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20460"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38092"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40884"},{"issue":"10","key":"e_1_2_11_9_1","first-page":"3225","article-title":"New medications are needed for children with juvenile idiopathic arthritis [abstract]","volume":"71","author":"Brunner H","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(18)30034-8"},{"key":"e_1_2_11_11_1","unstructured":"US Food and Drug Administration.XELJANZ\u00ae (tofacitinib): highlights of prescribing information. 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