The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia

BackgroundDifferences in the clinical efficacy and adverse drug reactions (ADRs) of eltrombopag (ELT) in children with immune thrombocytopenia (ITP) may be positively correlated with the serum trough concentration of ELT. Individual pharmacokinetic variations primarily contribute to differences in E...

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Main Authors: Nan Wang, Shuyue Dong, Yixin Sun, Jingjing Liu, Zhifa Wang, Jingyao Ma, Xiaoling Wang, Runhui Wu, Xiaoling Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1597641/full
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author Nan Wang
Nan Wang
Shuyue Dong
Yixin Sun
Yixin Sun
Jingjing Liu
Jingjing Liu
Zhifa Wang
Jingyao Ma
Xiaoling Wang
Runhui Wu
Xiaoling Cheng
author_facet Nan Wang
Nan Wang
Shuyue Dong
Yixin Sun
Yixin Sun
Jingjing Liu
Jingjing Liu
Zhifa Wang
Jingyao Ma
Xiaoling Wang
Runhui Wu
Xiaoling Cheng
author_sort Nan Wang
collection DOAJ
description BackgroundDifferences in the clinical efficacy and adverse drug reactions (ADRs) of eltrombopag (ELT) in children with immune thrombocytopenia (ITP) may be positively correlated with the serum trough concentration of ELT. Individual pharmacokinetic variations primarily contribute to differences in ELT concentration among individuals. This study is the first to establish an expected concentration reference range for ELT in treating pediatric persistent/chronic ITP (P/CITP) across different age-groups.MethodsA total of 94 patients with 111 serum trough concentrations were analyzed to validate this range. The median age of patients was 7.68 (5.35, 10.21) years, and 44.7% (42/49) of them were male.ResultsSubgroup analyses revealed significant differences in ELT concentration related to the age, efficacy, and ADR occurrence. The expected concentration reference range was determined using the dose-related concentration (DRC) factor combined with the ELT dosage. The DRC factor ranges were as follows: 0.083–0.216 (mg/L)/mg in children aged 1–6 years, 0.058–0.125 (mg/L)/mg in children aged 7–12 years, and 0.043–0.097 (mg/L)/mg in children aged 13–18 years. Among patients with measured trough concentrations within the expected reference range, 84.3% (59/70) achieved response/complete response (R/CR) and 88.6% (62/70) did not experience ADR.ConclusionSerum trough concentration monitoring based on the established reference ranges could enhance the precision of individualized ELT therapy in pediatric ITP patients.
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spelling doaj-art-b87b263f373245708ef3f2e1ff4b454c2025-08-21T05:27:29ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.15976411597641The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopeniaNan Wang0Nan Wang1Shuyue Dong2Yixin Sun3Yixin Sun4Jingjing Liu5Jingjing Liu6Zhifa Wang7Jingyao Ma8Xiaoling Wang9Runhui Wu10Xiaoling Cheng11Department of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, ChinaDepartment of Hematology, Beijing Children’s Hospital, Hemophilia Comprehensive Care Center, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaBeijing Children’s Hospital, Clinical Research Center, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Children’s Hospital, Hemophilia Comprehensive Care Center, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Pediatric, Beijing Shijitan Hospital of Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Children’s Hospital, Hemophilia Comprehensive Care Center, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Children’s Hospital, Hemophilia Comprehensive Care Center, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaDepartment of Hematology, Beijing Children’s Hospital, Hemophilia Comprehensive Care Center, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Children’s Hospital, Capital Medical University, Beijing, ChinaBackgroundDifferences in the clinical efficacy and adverse drug reactions (ADRs) of eltrombopag (ELT) in children with immune thrombocytopenia (ITP) may be positively correlated with the serum trough concentration of ELT. Individual pharmacokinetic variations primarily contribute to differences in ELT concentration among individuals. This study is the first to establish an expected concentration reference range for ELT in treating pediatric persistent/chronic ITP (P/CITP) across different age-groups.MethodsA total of 94 patients with 111 serum trough concentrations were analyzed to validate this range. The median age of patients was 7.68 (5.35, 10.21) years, and 44.7% (42/49) of them were male.ResultsSubgroup analyses revealed significant differences in ELT concentration related to the age, efficacy, and ADR occurrence. The expected concentration reference range was determined using the dose-related concentration (DRC) factor combined with the ELT dosage. The DRC factor ranges were as follows: 0.083–0.216 (mg/L)/mg in children aged 1–6 years, 0.058–0.125 (mg/L)/mg in children aged 7–12 years, and 0.043–0.097 (mg/L)/mg in children aged 13–18 years. Among patients with measured trough concentrations within the expected reference range, 84.3% (59/70) achieved response/complete response (R/CR) and 88.6% (62/70) did not experience ADR.ConclusionSerum trough concentration monitoring based on the established reference ranges could enhance the precision of individualized ELT therapy in pediatric ITP patients.https://www.frontiersin.org/articles/10.3389/fphar.2025.1597641/fulleltrombopagimmune thrombocytopeniachildrenindividualized treatmenttherapeutic drug monitoring
spellingShingle Nan Wang
Nan Wang
Shuyue Dong
Yixin Sun
Yixin Sun
Jingjing Liu
Jingjing Liu
Zhifa Wang
Jingyao Ma
Xiaoling Wang
Runhui Wu
Xiaoling Cheng
The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
Frontiers in Pharmacology
eltrombopag
immune thrombocytopenia
children
individualized treatment
therapeutic drug monitoring
title The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
title_full The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
title_fullStr The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
title_full_unstemmed The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
title_short The establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
title_sort establishment of an expected concentration reference range for eltrombopag in the individualized treatment of pediatric immune thrombocytopenia
topic eltrombopag
immune thrombocytopenia
children
individualized treatment
therapeutic drug monitoring
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1597641/full
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