学術雑誌論文

学術雑誌論文

text

Clinical Pharmacology and Therapeutics. 2024, 115(2), p. 239-247

Model-Informed Vancomycin Dosing Optimization to Address Delayed Renal Maturation in Infants and Young Children with Critical Congenital Heart Disease

John Wiley and Sons Inc

英語

text

2024-02-01

https://doi.org/10.1002/cpt.3095

This is the peer reviewed version of the following article, Shimamoto Y., Fukushima K., Mizuno T., et al. Model-Informed Vancomycin Dosing Optimization to Address Delayed Renal Maturation in Infants and Young Children with Critical Congenital Heart Disease. Clinical Pharmacology and Therapeutics 115, 239 (2024), which has been published in final form at https://doi.org/10.1002/cpt.3095. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

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 (60–80 mg/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 days–13 years old) for population PK analysis. The PK model was developed using a two-compartment model with allometrically scaled body weight, estimated glomerular filtration rate (eGFR), and postmenstrual age as covariates. The observed clearance in patients aged ≤ 1 year and 1–2 years was 33% and 40% lower compared with that of non-CCHD patients, respectively, indicating delayed renal maturation in patients with CCHD. Simulation analyses suggested VCM doses of 25 mg/kg/day (age ≤ 3 months, eGFR 40 mL/min/1.73 m2) and 35 mg/kg/day (3 months < age ≤ 3 years, eGFR 60 mL/min/1.73 m2). In conclusion, this study revealed delayed renal maturation in children with CCHD, could be due to cyanosis and low cardiac output. Model-informed simulations identified the lower VCM doses for children with CCHD compared with standard pediatric guidelines.

This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

94584

Model-Informed Vancomycin Dosing Optimization to Address Delayed Renal Maturation in Infants and Young Children with Critical Congenital Heart Disease

John Wiley and Sons Inc

英語

2024-02-01

Clinical Pharmacology and Therapeutics

115

2

239

247

https://doi.org/10.1002/cpt.3095

https://hdl.handle.net/11094/94584