{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:15:44Z","timestamp":1778314544734,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T00:00:00Z","timestamp":1556841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With increasing interest in enrolling adolescent patients in adult trials, a question often arises: when can pediatric patients use adult dosages? For currently approved therapeutic monoclonal antibodies (mAbs) with equivalent adult and pediatric indications, body weight thresholds for pediatric patients to receive adult doses vary from 30 to 75\u00a0kg. Our objective is to determine if a consistent weight threshold can be recommended for therapeutic mAbs with wide therapeutic windows. Simulations were run to predict exposure using a population pharmacokinetic model describing the typical PK characteristics of a mAb with linear elimination. Simulated steady\u2010state areas under the concentration\u2010time curves (AUC<jats:sub>ss<\/jats:sub>) were compared between pediatric and adult populations. Exponent values of 0.50, 0.75, and 1.0 for the allometric relationship of weight on clearance were also evaluated. Following administration of the same fixed adult dosage in pediatric subjects above a given threshold, median AUC<jats:sub>ss<\/jats:sub> in the pediatric subjects increased with decreasing weight thresholds. Pediatrics with a minimum weight of 40\u00a0kg had median AUC<jats:sub>ss<\/jats:sub> within 20% to 30% above adult median AUC<jats:sub>ss<\/jats:sub> when the reference adult population had a median weight \u226480\u00a0kg. Higher relative pediatric exposures were seen in lower\u2010weight pediatric subjects when the weight exponent on clearance was &gt;0.75. Simulations suggested that a weight threshold of 40\u00a0kg could generally be considered for pediatric subjects to receive the adult dosage for therapeutic mAbs with linear pharmacokinetics. Weight threshold selection should be based on considerations of therapeutic index of the drug product, weight distribution of the reference adult population, and magnitude of weight effect on pharmacokinetic parameters.<\/jats:p>","DOI":"10.1002\/jcph.1434","type":"journal-article","created":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T08:29:35Z","timestamp":1556872175000},"page":"1309-1318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of Weight Thresholds for Pediatric Patients to Use Adult Dosage of Therapeutic Monoclonal Antibodies"],"prefix":"10.1002","volume":"59","author":[{"given":"Nicholas","family":"Yang","sequence":"first","affiliation":[{"name":"University of Pennsylvania Vagelos Program in Life Sciences and Management  Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa C.","family":"Xu","sequence":"additional","affiliation":[{"name":"The Hill School  Pottstown PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenling","family":"Yao","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development  LLC, Spring House PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/19420862.2015.989042"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2018.1415671"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-0997-4"},{"key":"e_1_2_10_5_1","unstructured":"US Food and Drug Administration.Pediatric study plans: content of and process for submitting initial pediatric study plans and amended initial pediatric study plans guidance for industry.https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm360507.pdf2016. 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