{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:42:48Z","timestamp":1790566968573,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"3","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\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>Abrocitinib is an oral Janus kinase 1 (JAK1) inhibitor currently approved in the United Kingdom for the treatment of moderate\u2010to\u2010severe atopic dermatitis (AD). As patients with AD may use medications to manage comorbidities, abrocitinib could be used concomitantly with hepatic and\/or renal transporter substrates. Therefore, we assessed the potential effect of abrocitinib on probe drugs and endogenous biomarker substrates for the drug transporters of interest. <jats:italic>In vitro<\/jats:italic> studies indicated that, among the transporters tested, abrocitinib has the potential to inhibit the activities of P\u2010glycoprotein (P\u2010gp), breast cancer resistance protein (BCRP), organic anion transporter 3 (OAT3), organic cation transporter 1 (OCT1), and multidrug and toxin extrusion protein 1 and 2K (MATE1\/2K). Therefore, subsequent phase I, two\u2010way crossover, open\u2010label studies in healthy participants were performed to assess the impact of abrocitinib on the pharmacokinetics of the transporter probe substrates dabigatran etexilate (P\u2010gp), rosuvastatin (BCRP and OAT3), and metformin (OCT2 and MATE1\/2K), as well as endogenous biomarkers for MATE1\/2K (N<jats:sup>1<\/jats:sup>\u2010methylnicotinamide (NMN)) and OCT1 (isobutyryl\u2010<jats:sub>L<\/jats:sub>\u2010carnitine (IBC)). Co\u2010administration with abrocitinib was shown to increase the plasma exposure of dabigatran by ~\u00a050%. In comparison, the plasma exposure and renal clearance of rosuvastatin and metformin were not altered with abrocitinib co\u2010administration. Similarly, abrocitinib did not affect the exposure of NMN or IBC. An increase in dabigatran exposure suggests that abrocitinib inhibits P\u2010gp activity. By contrast, a lack of impact on plasma exposure and\/or renal clearance of rosuvastatin, metformin, NMN, or IBC suggests that BCRP, OAT3, OCT1, and MATE1\/2K activity are unaffected by abrocitinib.<\/jats:p>","DOI":"10.1002\/cpt.2594","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T19:03:42Z","timestamp":1648494222000},"page":"665-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Evaluation of the Effect of Abrocitinib on Drug Transporters by Integrated Use of Probe Drugs and Endogenous Biomarkers"],"prefix":"10.1111","volume":"112","author":[{"given":"Manoli","family":"Vourvahis","sequence":"first","affiliation":[{"name":"Pfizer Inc.  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonkyung","family":"Byon","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Chang","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu","family":"Le","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  New York New York 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":"Daniela","family":"Graham","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakambari","family":"Tripathy","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Raha","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Luo","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumathy","family":"Mathialagan","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dowty","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. David","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  Groton Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimal","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2018.07.006"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.01.011"},{"key":"e_1_2_11_4_1","unstructured":"Japan's MHLW Approves Pfizer's Cibinqo\u00ae (abrocitinib) for Adults and Adolescents with Moderate to Severe Atopic Dermatitis.News release. Published September 30 2021. https:\/\/www.pfizer.com\/news\/press\u2010release\/press\u2010release\u2010detail\/japans\u2010mhlw\u2010approves\u2010pfizers\u2010cibinqor\u2010abrocitinib\u2010adults#:~:text=(NYSE: PFE) today announced and older with inadequate response. 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