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...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.933739/full |
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| author | Xuan Gao Zhu-Li Bian Xiao-Hong Qiao Xiao-Wen Qian Jun Li Guo-Mei Shen Hui Miao Yi Yu Jian-Hua Meng Xiao-Hua Zhu Jun-Ye Jiang Jun Le Ling Yu Hong-Sheng Wang Xiao-Wen Zhai |
| author_facet | Xuan Gao Zhu-Li Bian Xiao-Hong Qiao Xiao-Wen Qian Jun Li Guo-Mei Shen Hui Miao Yi Yu Jian-Hua Meng Xiao-Hua Zhu Jun-Ye Jiang Jun Le Ling Yu Hong-Sheng Wang Xiao-Wen Zhai |
| author_sort | Xuan Gao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-14T03:59:46Z |
| format | Article |
| id | doaj.art-edd67fbc734b4781a16a3c1190ae60c2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T03:59:46Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-edd67fbc734b4781a16a3c1190ae60c22022-12-22T02:13:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.933739933739Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic AnemiaXuan Gao0Zhu-Li Bian1Xiao-Hong Qiao2Xiao-Wen Qian3Jun Li4Guo-Mei Shen5Hui Miao6Yi Yu7Jian-Hua Meng8Xiao-Hua Zhu9Jun-Ye Jiang10Jun Le11Ling Yu12Hong-Sheng Wang13Xiao-Wen Zhai14Outpatient and Emergency Management Office, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Pediatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pediatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaOutpatient and Emergency Management Office, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaDepartment of Hematology and Oncology, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, ChinaCyclosporine (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.https://www.frontiersin.org/articles/10.3389/fphar.2022.933739/fullcyclosporinepopulation pharmacokineticsNONMEMacquired aplastic anemiapediatric patients |
| spellingShingle | Xuan Gao Zhu-Li Bian Xiao-Hong Qiao Xiao-Wen Qian Jun Li Guo-Mei Shen Hui Miao Yi Yu Jian-Hua Meng Xiao-Hua Zhu Jun-Ye Jiang Jun Le Ling Yu Hong-Sheng Wang Xiao-Wen Zhai Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia Frontiers in Pharmacology cyclosporine population pharmacokinetics NONMEM acquired aplastic anemia pediatric patients |
| 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 | cyclosporine population pharmacokinetics NONMEM acquired aplastic anemia pediatric patients |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.933739/full |
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