{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:21:19Z","timestamp":1791937279794,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":2928,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:p>This study was performed to estimate the population pharmacokinetic (PK) parameters of etanercept in pediatric juvenile rheumatoid arthritis (JRA) patients and to compare the steady\u2010state time\u2010concentration profiles between etanercept 0.8\u2010mg\/kg once\u2010weekly and 0.4\u2010mg\/kg twice\u2010weekly subcutaneous (SC) regimens by clinical trial simulation. To this end, mixed\u2010effect analysis (NONMEM, Version 5.1) was performed using the etanercept PK database consisting of 69 JRA patients (4\u201317 years). Based on the population PK parameters obtained herein, a Monte Carlo clinical trial simulation experiment was conducted to compare the PK profiles in 200 virtual JRA patients who randomly received either etanercept 0.4 mg\/kg SC twice weekly or 0.8 mg\/kg once weekly for 12 weeks. The following population PK model could adequately describe etanercept PK profiles for twice\u2010weekly SC dosing of 0.4 mg\/kg:<\/jats:p><jats:p><jats:disp-formula>\n<jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" position=\"anchor\" xlink:href=\"urn:x-wiley:00912700:media:JCPH1082:jcph_246_mu1\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic>\n<\/jats:disp-formula>\n<\/jats:p><jats:p>The means \u00b1 standard deviations of simulated trough concentrations for 0.8\u2010mg\/kg once\u2010weekly and 0.4\u2010mg\/kg twice\u2010weekly dosing regimens were 1.58 \u00b1 1.07 mg\/L and 1.92 \u00b1 1.09 mg\/L, respectively. Peaks during 0.8\u2010mg\/kg once\u2010weekly dosing (2.92 \u00b1 1.41 mg\/L) were only 11% higher than during 0.4 mg\/kg twice\u2010weekly dosing (2.62 \u00b1 1.23 mg\/L). In conclusion, the clinical trial simulation confirmed that 0.8\u2010mg\/kg once\u2010weekly and 0.4\u2010mg\/kg twice\u2010weekly SC regimens of etanercept are expected to yield overlapping steady\u2010state time\u2010concentration profiles, leading to equivalent clinical outcomes. This has been the basis of the recent Food and Drug Administration approval of the 0.8\u2010mg\/kg once\u2010weekly regimen in pediatric patients with JRA.<\/jats:p>","DOI":"10.1177\/0091270004271945","type":"journal-article","created":{"date-parts":[[2005,2,9]],"date-time":"2005-02-09T20:32:58Z","timestamp":1107981178000},"page":"246-256","source":"Crossref","is-referenced-by-count":68,"title":["Population Pharmacokinetic Analysis and Simulation of the Time\u2010Concentration Profile of Etanercept in Pediatric Patients With Juvenile Rheumatoid Arthritis"],"prefix":"10.1002","volume":"45","author":[{"given":"Dong\u2010Seok","family":"Yim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Buckwalter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Nestorov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl C.","family":"Peck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390817"},{"key":"e_1_2_5_3_2","first-page":"205","article-title":"Epidemiology of juvenile rheumatoid arthritis","volume":"3","author":"Petty RE","year":"1987","journal-title":"World Pediatr Child Care"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/322547a0"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00920793"},{"key":"e_1_2_5_6_2","first-page":"1544","article-title":"Patterns of cytokine production in psoriatic synovium","volume":"25","author":"Ritchlin C","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_5_7_2","first-page":"518","article-title":"Highly increased levels of tumor necrosis factor\u2010alpha and other proinflammatory cytokines in psoriatic arthritis synovial fluid","volume":"24","author":"Partsch G","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780391013"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.4.432"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01451007"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00917473"},{"key":"e_1_2_5_12_2","first-page":"1238","article-title":"Long\u2010term safety and efficacy of etanercept in patients with rheumatoid arthritis","volume":"28","author":"Moreland LW","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011303432201"},{"key":"e_1_2_5_14_2","first-page":"1181","article-title":"Absolute bioavailability of TNF receptor fusion protein following subcutaneous injection in healthy volunteers [abstract]","volume":"17","author":"Lebsack ME","year":"1997","journal-title":"Pharmacotherapy"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1345\/aph.19126"},{"key":"e_1_2_5_16_2","unstructured":"Enbrel (etanercept) [product information].1999. 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