{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:57:29Z","timestamp":1790621849217,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Canagliflozin was recently approved in type 2 diabetes mellitus (T2DM) patients \u226510 and &lt;18\u2009years old as a single agent dosed once daily (QD) or in a fixed\u2010dose combination with metformin dosed twice daily (BID). We characterize canagliflozin pharmacokinetics in paediatric patients with T2DM, compare estimated individual and simulated exposure metrics for QD and BID doses in paediatric patients and adults, and investigate the relationship between canagliflozin plasma concentrations and change from baseline HbA1c with QD and BID doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Paediatric population pharmacokinetics and pharmacokinetics\/pharmacodynamics models were based on the previously developed corresponding adult models, using Phase 1 and 3 study data, evaluating canagliflozin 100\u2010 or 300\u2010mg QD doses in paediatric patients with T2DM. Modelling encompassed exploratory analysis, external evaluation, model update and simulation of canagliflozin exposure metrics and HbA1c for QD and BID doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Estimated and simulated steady\u2010state area under the concentration\u2013time curve during 24\u2009h (AUC\n                      <jats:sub>24h<\/jats:sub>\n                      ) and maximum drug concentration were comparable between paediatric patients and adults for canagliflozin 100\u2010 or 300\u2010mg QD. Simulated steady\u2010state AUC\n                      <jats:sub>24h<\/jats:sub>\n                      was similar between QD and BID dosing for the same canagliflozin total daily dose in paediatric patients and adults with T2DM. QD to BID bridging was supported by simulated HbA1c and change from baseline in HbA1c in paediatric patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>No canagliflozin dose adjustments are required alone or in combination with metformin to ensure similar plasma exposures between paediatric and adult patients with T2DM, as well as similar HbA1c lowering between QD and BID dosing in paediatric patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70644","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:07:29Z","timestamp":1782976049000},"page":"3622-3633","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics and pharmacodynamics of canagliflozin in paediatric patients with type 2 diabetes mellitus"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0526-5318","authenticated-orcid":false,"given":"Nele","family":"Goeyvaerts","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0706-8783","authenticated-orcid":false,"given":"Per Olsson","family":"Gisleskog","sequence":"additional","affiliation":[{"name":"POG Pharmacometrics  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0959-3924","authenticated-orcid":false,"given":"Martine","family":"Neyens","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-745X","authenticated-orcid":false,"given":"Juan Jos\u00e9 Perez","family":"Ruixo","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1581-8431","authenticated-orcid":false,"given":"Saberi Rana","family":"Ali","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Titusville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Raritan New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-5200","authenticated-orcid":false,"given":"Oliver","family":"Ackaert","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2021.05.013"},{"issue":"6","key":"e_1_2_10_3_1","first-page":"401","article-title":"Type 2 diabetes mellitus in children and adolescents","volume":"45","author":"Kao KT","year":"2016","journal-title":"Aust Fam Physician"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(23)00025\u20106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010022\u201003172\u2010y"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2022.2061260"},{"key":"e_1_2_10_7_1","unstructured":"US FDA.INVOKANA\u00ae (canagliflozin) prescribing information Retrieved July 30 2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/204042s043lbl.pdf"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12852"},{"key":"e_1_2_10_9_1","unstructured":"EMA Invokana summary of product characteristics. Retrieved July 30 2025 https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/invokana-epar-product-information_en.pdf"},{"key":"e_1_2_10_10_1","unstructured":"Administration ATG Australian public assessment report for canagliflozin. Retrieved August 7 2025 https:\/\/www.tga.gov.au\/sites\/default\/files\/auspar-canagliflozin-140303.pdf"},{"key":"e_1_2_10_11_1","unstructured":"Corporation MTP CANAGLU\u00ae Japanese prescribing information Retrieved August 7 2025 https:\/\/medical.mt-pharma.co.jp\/di\/file\/dc\/can_a.pdf"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/6295345"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12626"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS\u201024\u201004017"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010015\u20100307\u2010x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13180"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010024\u201001444\u20106"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16182"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"29","article-title":"Estimated glomerular filtration rate explained","volume":"108","author":"Tarwater K","year":"2011","journal-title":"Mo Med"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv454"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70644","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:56:37Z","timestamp":1790618197000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":21,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/bcp.70644"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70644","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]}}}