{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:28:37Z","timestamp":1790602117640,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/06526\u20107"],"award-info":[{"award-number":["2014\/06526\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Ceftriaxone is a cephalosporin commonly used for the treatment of acute, severe infections; however, there are conflicting data on its disposition properties in children, making it a suitable case study for the evaluation of the appropriateness of extrapolation approaches based on exposure matching principles for paediatric patients and exploring the relevance of optimized protocol designs to characterize the pharmacokinetics in prospective studies in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 12 healthy adults receiving ceftriaxone (1\u00a0g IV) were available for the purpose of this investigation. A nonlinear mixed effects modelling approach was implemented in conjunction with ED\u2010optimality to identify suitable sampling schemes in children. In addition, estimates were derived of the probability of target attainment across the relevant weight range. Predictions were compared with published pharmacokinetic data and established dosing recommendations for children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A two\u2010compartment model with first\u2010order elimination best described the data, with body weight as a covariate on clearance (0.97\u2009L\/h) and\n                      <jats:italic>V<\/jats:italic>\n                      ss (8.83\u2009L). Doses derived through exposure matching were substantially lower than those currently recommended. A sampling scheme with four samples per subject (\n                      <jats:italic>t<\/jats:italic>\n                      \u2009=\u20090.17\u20130.25\u2009h, 0.7\u20131.2\u00a0h, 5.1\u20135.6\u00a0h and 11.5\u201312.0\u2009h postdose) was identified for the assessment of the pharmacokinetics of ceftriaxone in children.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our case study reveals the importance of considering factors other than developmental growth and maturation when extrapolating the efficacy of compounds such as ceftriaxone based on matching exposure and PKPD principles. It also highlights the need for optimized, informative study protocols for the accurate description of drug disposition properties in children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70709","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:01:17Z","timestamp":1788998477000},"source":"Crossref","is-referenced-by-count":1,"title":["Extrapolation and pharmacokinetic protocol design optimization for ceftriaxone as an exemplar for the development of antibiotics for children"],"prefix":"10.1002","author":[{"given":"Daniel Valente","family":"Neves","sequence":"first","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-6943","authenticated-orcid":false,"given":"Umberto","family":"Villani","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Therapeutics Group University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-4834","authenticated-orcid":false,"given":"Salvatore","family":"D'Agate","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Therapeutics Group University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Oosterholt","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; Therapeutics Group University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"de Carvalho Cavalli","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine Universidade de S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Carmona","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-4953","authenticated-orcid":false,"given":"Vera Lucia","family":"Lanchote","sequence":"additional","affiliation":[{"name":"Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"Committee for Medicinal Products for Human Use (CHMP).Addendum to the guideline on the evaluation of medicinal products indicated for treatment of bacterial infections to address paediatric\u2010specific clinical data requirements. 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