{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:19:51Z","timestamp":1787822391315,"version":"build-2784847793"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102023\u201000278597"],"award-info":[{"award-number":["RS\u20102023\u201000278597"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010NR069643"],"award-info":[{"award-number":["RS\u20102022\u2010NR069643"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010NR070856"],"award-info":[{"award-number":["RS\u20102022\u2010NR070856"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003661","name":"Korea Institute for Advancement of Technology","doi-asserted-by":"publisher","award":["RS\u20102024\u201000434342"],"award-info":[{"award-number":["RS\u20102024\u201000434342"]}],"id":[{"id":"10.13039\/501100003661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Sirolimus is currently used off\u2010label for paediatric patients with vascular anomalies. However, the optimal dosage regimen for paediatric patients remains controversial. This study aimed to determine the optimal dosing regimen of sirolimus in these patients using a population pharmacokinetic (PK) model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective study data (seven subjects) were used as the structural model without covariates, while the retrospective study data (21 subjects) were used as the structural model with size and maturation functions for evaluation. The model was assessed using general model\u2010building criteria, and a bootstrap stepwise covariate modelling method was used to identify relevant covariates. Simulations were performed for various scenarios to determine the optimal dosing regimen for maintaining sirolimus trough concentrations within a specific range. NONMEM software (Version 7.5) with the first\u2010order conditional estimation method with interaction was used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The final sirolimus model was developed using a two\u2010compartment model, which was implemented by a maturation function using postmenstrual age (PMA), allometrically scaled body weight to account for size differences, and haemoglobin as a covariate on clearance. Simulations were conducted to propose an optimal dosing regimen. A once\u2010daily dose of 0.01\u20130.1\u2009mg\/kg over 1\u2009month maintained the trough concentration within the range of 5\u201315\u2009ng\/mL, taking into account patient\u2010specific weight and the influence of haemoglobin constrained on PMA. The optimal dose varied by group, within the range of 0.06\u20130.09\u2009mg\/kg.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We developed a robust and reliable PK model of sirolimus for paediatric patients with vascular anomalies. Paediatric optimal dosing regimens should be based on individual growth patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70595","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:30:13Z","timestamp":1778643013000},"page":"3115-3123","source":"Crossref","is-referenced-by-count":0,"title":["Optimal dosing for vascular anomalies paediatric patients with population pharmacokinetic model of sirolimus"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0005-6535","authenticated-orcid":false,"given":"Seongmee","family":"Jeong","sequence":"first","affiliation":[{"name":"College of Pharmacy Chungnam National University  Deajeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungryul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Samsung Medical Center  Seoul South 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