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Model-Informed individualized dosage regimen of sirolimus in pediatric patients with intractable lymphatic malformations.
Liu, Bo; Zhang, Xuexi; Zhao, Yiming; Xu, Xiaolin; Wang, Shengcai; Wang, Xiaoling; Cheng, Xiaoling.
Afiliación
  • Liu B; Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China; Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
  • Zhang X; Department of Otorhinolaryngology-Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
  • Zhao Y; Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
  • Xu X; Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
  • Wang S; Department of Otorhinolaryngology-Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
  • Wang X; Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: wangxiaoling@bch.com.cn.
  • Cheng X; Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. Electronic address: chengxiaoling1224@163.com.
Eur J Pharm Sci ; 200: 106837, 2024 Sep 01.
Article en En | MEDLINE | ID: mdl-38960206
ABSTRACT
Intractable lymphatic malformations (iLM) pose a significant threat to affected children, demonstrating limited responses to conventional treatments. Sirolimus, effectively inhibiting endothelial cell proliferation in lymphatic vessels, plays a crucial role in iLM treatment. However, the drug's narrow therapeutic window and substantial interindividual variability necessitate customized dosing strategies. This study aims to establish a Population Pharmacokinetic Model (PopPK model) for sirolimus in pediatric iLM patients, identifying quantitative relationships between covariates and sirolimus clearance and volume of distribution. Initial dosages are recommended based on a target concentration range of 5-15 ng/mL. Retrospective data from our institution, encompassing 53 pediatric patients with 275 blood concentration results over the past five years (average age 4.64 ± 4.19 years), constituted the foundation of this analysis. The final model, adopting a first-order absorption and elimination single-compartment model, retained age as the sole covariate. Results indicated a robust correlation between apparent clearance (CL/F) at 5.56 L/h, apparent volume of distribution (V/F) at 292.57 L, and age. Monte Carlo simulation guided initial dosages for patients aged 0-18 years within the target concentration range. This study presents the first PopPK model using a large Therapeutic Drug Monitoring (TDM) database to describe personalized sirolimus dosing for pediatric iLM patients, contributing to pharmacokinetic guidance and potentially improving long-term clinical outcomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sirolimus / Anomalías Linfáticas / Modelos Biológicos Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sirolimus / Anomalías Linfáticas / Modelos Biológicos Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos