{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T20:19:16Z","timestamp":1771877956109,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002066","name":"GlaxoSmithKline foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The US Food and Drug Administration's Animal Rule allows for the approval of drugs when human efficacy studies are not ethical. While the therapeutic doses of raxibacumab, a monoclonal antibody for the prophylaxis and treatment of inhalational anthrax, have been based on pharmacokinetic data from adult subjects, its disposition in children has not been investigated in clinical trials. Here we evaluate the effect of demographic covariates and maturation processes on the pharmacokinetics of raxibacumab and explore opportunities for the optimisation of paediatric doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A population pharmacokinetic model was used as basis for the extrapolation of raxibacumab disposition from adults to children. Different extrapolation scenarios, including weight\u2010banded dosing regimens, were considered to assess the effect of growth and maturation on the pharmacokinetic parameters of interest. Area under the concentration\u2013time curve, maximum plasma concentration and the time of serum raxibacumab concentrations greater than or equimolar to the highest serum protective antigen concentrations observed for at least 28\u2009days in any monkey challenged with <jats:styled-content style=\"fixed-case\"><jats:italic>Bacillus anthracis<\/jats:italic><\/jats:styled-content> that died were derived and compared with the currently approved US doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on practical considerations, a weight\u2010banded dosing regimen consisting of 4 dose levels (75\u2009mg\/kg for individuals \u22641.5\u00a0kg, 55\u2009mg\/kg for individuals &lt;10\u00a0kg, 45\u2009mg\/kg for individuals &lt;50\u2009kg, 40\u2009mg\/kg for all individuals &gt;50\u2009kg) was required to optimise target exposure across the paediatric population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Age\u2010related maturation processes may affect raxibacumab clearance in very young patients. The proposed dosing regimens take into account effects of body weight and maturation processes on the elimination of raxibacumab.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14893","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T17:50:44Z","timestamp":1620755444000},"page":"4709-4717","source":"Crossref","is-referenced-by-count":6,"title":["Extrapolation and dosing recommendations for raxibacumab in children from birth to age &lt;18\u2009years"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4346-0088","authenticated-orcid":false,"given":"Sean P.","family":"Oosterholt","sequence":"first","affiliation":[{"name":"Clinical Pharmacology &amp; Therapeutics Group University College London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-1430","authenticated-orcid":false,"given":"Oscar","family":"Della Pasqua","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Therapeutics Group University College London  UK"},{"name":"Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline  Brentford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Code of Federal Regulations.Approval of new drugs when human efficacy studies are not ethical or feasible. Title 21 Food and Drug Administration 2002. Available at:https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?CFRPart=314&showFR=1&subpartNode=21:5.0.1.1.4.9. Last accessed on May 11 2020."},{"key":"e_1_2_10_3_1","unstructured":"Code of Federal Regulations.Approval of biological products when human efficacy studies are not ethical or feasible. Title 21 Food and Drug Administration 2002. Available at:https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfcfr\/CFRSearch.cfm?CFRPart=601&showFR=1&subpartNode=21:7.0.1.1.2.8. Last accessed on May 11 2020."},{"key":"e_1_2_10_4_1","unstructured":"Food and Drug Administration.CDER DRUG AND BIOLOGIC ANIMAL RULE APPROVALS.2018. Available at:https:\/\/www.fda.gov\/media\/107839\/download. 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