{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:10:39Z","timestamp":1789175439453,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T00:00:00Z","timestamp":1516752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ABT\u2010122 is an IgG1 dual\u2010variable domain immunoglobulin that specifically blocks TNF\u2010\u03b1 and IL\u201017A. This work characterized ABT\u2010122 pharmacokinetics using nonlinear mixed\u2010effects modeling and ABT\u2010122 serum concentrations from 72 healthy subjects, 196 subjects with rheumatoid arthritis (RA), and 144 subjects with psoriatic arthritis (PsA) enrolled in 4 phase 1 and 2 phase 2 studies (0.1\u201310\u00a0mg\/kg intravenously and 0.3\u20133\u00a0mg\/kg subcutaneous single doses and 0.3\u20133.0\u00a0mg\/kg subcutaneous and 60\u2013240\u00a0mg subcutaneous doses weekly or every other week). A 2\u2010compartment model with a combination of linear clearance (0.419\u00a0L\/day) and nonlinear clearance (relevant only at low doses; V<jats:sub>max<\/jats:sub>and K<jats:sub>m<\/jats:sub>of 0.155\u00a0mg\/day and 0.0458\u00a0mg\/L, respectively) described ABT\u2010122 pharmacokinetics. Subcutaneous bioavailability was 35%\u201358% across formulations and populations. Body weight was a significant covariate for ABT\u2010122 clearance, with subjects with body weight of 140\u00a0and 40\u00a0kg estimated to have 38% lower and 43% higher ABT\u2010122 AUC, respectively, compared with a 70\u2010kg reference subject. ABT\u2010122 antidrug antibody (ADA) titer (ADA incidence, 47%; 0 to 519\u00a0000 titer range in the data set) was a continuous covariate on ABT\u2010122 clearance. An ADA titer of 100 units resulted in a 5\u2010fold increase in clearance. Sex, age, and baseline serum albumin or baseline C\u2010reactive protein level did not impact ABT\u2010122 exposure. Fixed\u2010effects and random\u2010effects parameters were estimated with a relative standard error of \u226417% and \u226428%, respectively, and the model was qualified using bootstrap analysis and visual predictive checks. This analysis characterized ABT\u2010122 exposure across populations and supported exposure\u2013response analyses of ABT\u2010122 efficacy in RA and PsA.<\/jats:p>","DOI":"10.1002\/jcph.1068","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T14:07:09Z","timestamp":1516802829000},"page":"803-813","source":"Crossref","is-referenced-by-count":15,"title":["Population Pharmacokinetics of the TNF\u2010\u03b1 and IL\u201017A Dual\u2010Variable Domain Antibody ABT\u2010122 in Healthy Volunteers and Subjects With Psoriatic or Rheumatoid Arthritis: Analysis of Phase 1 and 2 Clinical Trials"],"prefix":"10.1002","volume":"58","author":[{"given":"Amit","family":"Khatri","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Othman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-014-0414-y"},{"key":"e_1_2_9_3_1","unstructured":"Enbrel [package insert]. 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