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Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia
Cyclosporine (CsA) is a component of the first-line treatment for acquired aplastic anemia (acquired AA) in pediatric patients. This study aimed to develop a population pharmacokinetic (PK) model of CsA in Chinese pediatric patients with acquired AA to inform individual dosage regimens. A total of 6...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377374/ https://www.ncbi.nlm.nih.gov/pubmed/35979231 http://dx.doi.org/10.3389/fphar.2022.933739 |
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author | Gao, Xuan Bian, Zhu-Li Qiao, Xiao-Hong Qian, Xiao-Wen Li, Jun Shen, Guo-Mei Miao, Hui Yu, Yi Meng, Jian-Hua Zhu, Xiao-Hua Jiang, Jun-Ye Le, Jun Yu, Ling Wang, Hong-Sheng Zhai, Xiao-Wen |
author_facet | Gao, Xuan Bian, Zhu-Li Qiao, Xiao-Hong Qian, Xiao-Wen Li, Jun Shen, Guo-Mei Miao, Hui Yu, Yi Meng, Jian-Hua Zhu, Xiao-Hua Jiang, Jun-Ye Le, Jun Yu, Ling Wang, Hong-Sheng Zhai, Xiao-Wen |
author_sort | Gao, Xuan |
collection | PubMed |
description | Cyclosporine (CsA) is a component of the first-line treatment for acquired aplastic anemia (acquired AA) in pediatric patients. This study aimed to develop a population pharmacokinetic (PK) model of CsA in Chinese pediatric patients with acquired AA to inform individual dosage regimens. A total of 681 CsA whole blood concentrations and laboratory data of 157 pediatric patients with acquired AA were retrospectively collected from two hospitals in Shanghai. A nonlinear mixed-effect model approach was used to build the population PK model. Potential covariate effects of age, body weight, and biochemical measurements (renal and liver functions) on CsA PK disposition were evaluated. Model fit was assessed using the basic goodness of fit and a visual predictive check. The CsA concentration data were accurately described using a two-compartment disposition model with first-order absorption and elimination. Body weight value was implemented as a fixed allometric function on all clearance and volume of distribution parameters. Total bilirubin level was identified as a significant covariate on apparent clearance (CL/F), with a 1.07% reduction per 1 nmol/L rise in total bilirubin level. The final estimates for CL/F and central volume (Vc/F) were 29.1 L/h and 325 L, respectively, for a typical 28 kg child. Other covariates (e.g., gender, age, albumin, hemoglobin, hematocrit, serum creatinine, and concomitant medication) did not significantly affect the PK properties of CsA. This population PK model, along with a maximum a posteriori Bayesian approach, could estimate individual PK parameters in pediatric patients with acquired AA to conduct individual CsA therapy. |
format | Online Article Text |
id | pubmed-9377374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93773742022-08-16 Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia Gao, Xuan Bian, Zhu-Li Qiao, Xiao-Hong Qian, Xiao-Wen Li, Jun Shen, Guo-Mei Miao, Hui Yu, Yi Meng, Jian-Hua Zhu, Xiao-Hua Jiang, Jun-Ye Le, Jun Yu, Ling Wang, Hong-Sheng Zhai, Xiao-Wen Front Pharmacol Pharmacology Cyclosporine (CsA) is a component of the first-line treatment for acquired aplastic anemia (acquired AA) in pediatric patients. This study aimed to develop a population pharmacokinetic (PK) model of CsA in Chinese pediatric patients with acquired AA to inform individual dosage regimens. A total of 681 CsA whole blood concentrations and laboratory data of 157 pediatric patients with acquired AA were retrospectively collected from two hospitals in Shanghai. A nonlinear mixed-effect model approach was used to build the population PK model. Potential covariate effects of age, body weight, and biochemical measurements (renal and liver functions) on CsA PK disposition were evaluated. Model fit was assessed using the basic goodness of fit and a visual predictive check. The CsA concentration data were accurately described using a two-compartment disposition model with first-order absorption and elimination. Body weight value was implemented as a fixed allometric function on all clearance and volume of distribution parameters. Total bilirubin level was identified as a significant covariate on apparent clearance (CL/F), with a 1.07% reduction per 1 nmol/L rise in total bilirubin level. The final estimates for CL/F and central volume (Vc/F) were 29.1 L/h and 325 L, respectively, for a typical 28 kg child. Other covariates (e.g., gender, age, albumin, hemoglobin, hematocrit, serum creatinine, and concomitant medication) did not significantly affect the PK properties of CsA. This population PK model, along with a maximum a posteriori Bayesian approach, could estimate individual PK parameters in pediatric patients with acquired AA to conduct individual CsA therapy. Frontiers Media S.A. 2022-07-26 /pmc/articles/PMC9377374/ /pubmed/35979231 http://dx.doi.org/10.3389/fphar.2022.933739 Text en Copyright © 2022 Gao, Bian, Qiao, Qian, Li, Shen, Miao, Yu, Meng, Zhu, Jiang, Le, Yu, Wang and Zhai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Gao, Xuan Bian, Zhu-Li Qiao, Xiao-Hong Qian, Xiao-Wen Li, Jun Shen, Guo-Mei Miao, Hui Yu, Yi Meng, Jian-Hua Zhu, Xiao-Hua Jiang, Jun-Ye Le, Jun Yu, Ling Wang, Hong-Sheng Zhai, Xiao-Wen Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia |
title | Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia |
title_full | Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia |
title_fullStr | Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia |
title_full_unstemmed | Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia |
title_short | Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia |
title_sort | population pharmacokinetics of cyclosporine in chinese pediatric patients with acquired aplastic anemia |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377374/ https://www.ncbi.nlm.nih.gov/pubmed/35979231 http://dx.doi.org/10.3389/fphar.2022.933739 |
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