{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:48:58Z","timestamp":1761742138890,"version":"build-2065373602"},"reference-count":18,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To further assess the pharmacokinetic\/pharmacodynamic characteristics of methoxy polyethylene glycol\u2010epoetin \u03b2 (continuous erythropoiesis receptor activator; C.E.R.A.) in children with chronic kidney disease (CKD) aged 3\u2009months to 18\u2009years undergoing different dialysis modalities and receiving intravenous\/subcutaneous doses, compared with adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The population pharmacokinetic and pharmacokinetic\/pharmacodynamic C.E.R.A. models, developed using intravenous and subcutaneous data from adults with various dialysis modalities and intravenous data from children receiving haemodialysis, were updated with subcutaneous data from children receiving peritoneal dialysis or predialysis from the phase II paediatric study NH19708 (SKIPPER). Observed and predicted median C.E.R.A. doses and mean haemoglobin levels (indicative of response) were compared using paediatric clinical trials and real\u2010world data from the MH40258 registry study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The pharmacokinetic analysis in 627 patients, including 103 children aged 0.5\u201317\u2009years, revealed that subcutaneous bioavailability in children was 2.18 times higher than in adults (67.1% [95% confidence interval: 52.6\u201381.6]). Distribution volume increased with weight and age, and clearance increased with weight. Incorporating dialysis modality as a covariate improved the pharmacokinetic\/pharmacodynamic model's fit to haemoglobin data. The agreement of observed and predicted paediatric data with real\u2010world data underscores the model's predictive performance and C.E.R.A.\u2019s replicable clinical trial effects in clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This analysis enhanced our knowledge of C.E.R.A.\u2019s effects in children with CKD, confirming its pharmacokinetic\/pharmacodynamic characteristics align with adults. Comparison of clinical trial data, model prediction, and real\u2010world data show that C.E.R.A. intravenous and subcutaneous dosing and procedures in adults and children provide adequate control of haemoglobin in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70165","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:04:19Z","timestamp":1752570259000},"page":"3189-3200","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic and pharmacodynamic modelling of continuous erythropoiesis receptor activator in children: A comprehensive analysis and real\u2010world data validation"],"prefix":"10.1002","volume":"91","author":[{"given":"Samer","family":"Mouksassi","sequence":"first","affiliation":[{"name":"Certara  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Centre for Pediatric and Adolescent Medicine, Clinic 1, Pediatric Nephrology Heidelberg University  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley A.","family":"Warady","sequence":"additional","affiliation":[{"name":"Children's Mercy Kansas City University of Missouri \u2013 Kansas City  MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus P.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg, Centre for Pediatric and Adolescent Medicine, Clinic 1, Pediatric Nephrology Heidelberg University  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie Meyer","family":"Reigner","sequence":"additional","affiliation":[{"name":"F.Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Studer","sequence":"additional","affiliation":[{"name":"F.Hoffmann\u2010La Roche Ltd  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9011-5431","authenticated-orcid":false,"given":"Pascal","family":"Chanu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Genentech\/Roche  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2515-5357","authenticated-orcid":false,"given":"Nicolas","family":"Frey","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development Roche Innovation Center  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"volume-title":"MIRCERA (methoxy polyethylene glycol\u2010epoetin beta). Summary of product characteristics","author":"Roche Registration GmbH","key":"e_1_2_10_2_1"},{"volume-title":"MIRCERA\u00ae (methoxy polyethylene glycol\u2010epoetin beta). Prescribing information","author":"Vifor (International) Inc","key":"e_1_2_10_3_1"},{"volume-title":"Study to determine optimum intravenous starting dose of MIRCERA for treatment of pediatric participants with anemia and chronic kidney disease on hemodialysis","author":"ClinicalTrials.gov","key":"e_1_2_10_4_1"},{"volume-title":"Ascertain the optimal starting dose of Mircera given subcutaneously for maintenance treatment of anemia in pediatric patients with chronic kidney disease on dialysis or not yet on dialysis","author":"ClinicalTrials.gov","key":"e_1_2_10_5_1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03570417"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2022.11.006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009343931"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20101241.2006.01214.x"},{"volume-title":"A study of Mircera in anemic patients with chronic kidney disease not yet on dialysis","author":"ClinicalTrials.gov","key":"e_1_2_10_10_1"},{"volume-title":"An open\u2010label, randomized, multicenter, parallel group study to demonstrate correction of anemia using intravenous injections of RO0503821 in patients with chronic kidney disease who are on dialysis","author":"EU Clinical Trials Register","key":"e_1_2_10_11_1"},{"volume-title":"A study of intravenous Mircera for the treatment of anemia in dialysis patients","author":"ClinicalTrials.gov","key":"e_1_2_10_12_1"},{"volume-title":"A study of subcutaneous Mircera for the treatment of anemia in dialysis patients","author":"ClinicalTrials.gov","key":"e_1_2_10_13_1"},{"volume-title":"The visual predictive check \u2013 superiority to standard diagnostic (Rorschach) plots","author":"Holford N","key":"e_1_2_10_14_1"},{"issue":"2","key":"e_1_2_10_15_1","first-page":"S289","article-title":"The concise guide to PHARMACOLOGY 2023\/24: enzymes","volume":"180","author":"Alexander SPH","year":"2023","journal-title":"Br J Pharmacol"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14186"},{"volume-title":"Aranesp (darbepoetin alfa). Summary of product characteristics","author":"Amgen Europe BV","key":"e_1_2_10_17_1"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272\u2010020\u201000382\u20107"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/1744\u20109987.12775"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T07:21:12Z","timestamp":1761722472000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/bcp.70165"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70165","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"type":"print","value":"0306-5251"},{"type":"electronic","value":"1365-2125"}],"subject":[],"published":{"date-parts":[[2025,7,15]]}}}