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Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia.
Zhang, Wei; Chang, Li-Xian; Zhao, Bei-Bei; Zheng, Yi; Shan, Dan-Dan; Tang, Bo-Hao; Yang, Fan; Zhou, Yue; Hao, Guo-Xiang; Zhang, Ya-Hui; van den Anker, John; Zhu, Xiao-Fan; Zhang, Li; Zhao, Wei.
Afiliación
  • Zhang W; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Chang LX; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
  • Zhao BB; Tianjin Institutes of Health Science, Tianjin, China.
  • Zheng Y; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
  • Shan DD; Tianjin Institutes of Health Science, Tianjin, China.
  • Tang BH; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Yang F; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zhou Y; Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Hao GX; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zhang YH; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • van den Anker J; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zhu XF; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • Zhang L; Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • Zhao W; Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.
J Clin Pharmacol ; 64(8): 932-943, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38497347
ABSTRACT
Eltrombopag was approved as a first-line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA), are limited. We performed a prospective, single-arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty-three AA children with an average age of 7.9 (range of 3.0-14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty-three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele-T carrier of adenosine triphosphate-binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild-type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight-adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pirazoles / Benzoatos / Hidrazinas / Anemia Aplásica Límite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: J Clin Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Pirazoles / Benzoatos / Hidrazinas / Anemia Aplásica Límite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: J Clin Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China