{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:43:46Z","timestamp":1791434626700,"version":"4.3.3"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Ensuring safe and effective drug therapy in infants and young children often requires accounting for growth and organ development; however, data on organ function maturation are scarce for special populations, such as infants with congenital diseases. Children with critical congenital heart disease (CCHD) often require multiple staged surgeries depending on their age and disease severity. Vancomycin (VCM) is used to treat postoperative infections; however, the standard pediatric dose (60\u201380\u2009mg\/kg\/day) frequently results in overexposure in children with CCHD. In this study, we characterized the maturation of VCM clearance in pediatric patients with CCHD and determined the appropriate dosing regimen using population pharmacokinetic (PK) modeling and simulations. We analyzed 1,254 VCM serum concentrations from 152 postoperative patients (3\u2009days\u201313\u2009years old) for population PK analysis. The PK model was developed using a two\u2010compartment model with allometrically scaled body weight, estimated glomerular filtration rate (eGFR), and postmenstrual age as covariates. The observed clearance in patients aged \u2264\u20091\u2009year and 1\u20132\u2009years was 33% and 40% lower compared with that of non\u2010CCHD patients, respectively, indicating delayed renal maturation in patients with CCHD. Simulation analyses suggested VCM doses of 25\u2009mg\/kg\/day (age\u2009\u2264\u20093\u2009months, eGFR 40\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>) and 35\u2009mg\/kg\/day (3\u2009months &lt; age\u2009\u2264\u20093\u2009years, eGFR 60\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>). In conclusion, this study revealed delayed renal maturation in children with CCHD, could be due to cyanosis and low cardiac output. Model\u2010informed simulations identified the lower VCM doses for children with CCHD compared with standard pediatric guidelines.<\/jats:p>","DOI":"10.1002\/cpt.3095","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T18:36:07Z","timestamp":1700764567000},"page":"239-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Model\u2010Informed Vancomycin Dosing Optimization to Address Delayed Renal Maturation in Infants and Young Children with Critical Congenital Heart Disease"],"prefix":"10.1002","volume":"115","author":[{"given":"Yuko","family":"Shimamoto","sequence":"first","affiliation":[{"name":"Department of Pharmacy National Cerebral and Cardiovascular Center  Suita Osaka Japan"},{"name":"Department of Hospital Pharmacy, Graduate School of Medicine Osaka University  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-9826","authenticated-orcid":false,"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiovascular Surgery National Cerebral and Cardiovascular Center  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology National Cerebral and Cardiovascular Center  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Maeda","sequence":"additional","affiliation":[{"name":"Center for Advanced Education and Research in Pharmaceutical Sciences Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences Osaka University  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Graduate School of Medicine Osaka University  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,10]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.58.2.259"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.169"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1991"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008030287"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra035092"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-017-2122-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2010.03364.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03802.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2458"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14620"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1980"},{"key":"e_1_2_11_12_1","first-page":"249","article-title":"Birthweight of infants with congenital heart disease","volume":"132","author":"Levy R.J.","year":"1978","journal-title":"Am. 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