The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study
Aims: The aims of the study were to 1) establish a population pharmacokinetic (Pop-PK) model for busulfan in Chinese pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and then estimate busulfan exposure and 2) explore the association between busulfan exposure and clinical...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.905879/full |
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| author | Xiaohuan Du Xiaohuan Du Chenrong Huang Chenrong Huang Ling Xue Ling Xue Zheng Jiao Min Zhu Jie Li Jun Lu Peifang Xiao Xuemei Zhou Chenmei Mao Zengyan Zhu Ji Dong Xiaoxue Liu Zhiyao Chen Shichao Zhang Yiduo Ding Shaoyan Hu Liyan Miao Liyan Miao Liyan Miao |
| author_facet | Xiaohuan Du Xiaohuan Du Chenrong Huang Chenrong Huang Ling Xue Ling Xue Zheng Jiao Min Zhu Jie Li Jun Lu Peifang Xiao Xuemei Zhou Chenmei Mao Zengyan Zhu Ji Dong Xiaoxue Liu Zhiyao Chen Shichao Zhang Yiduo Ding Shaoyan Hu Liyan Miao Liyan Miao Liyan Miao |
| author_sort | Xiaohuan Du |
| collection | DOAJ |
| description | Aims: The aims of the study were to 1) establish a population pharmacokinetic (Pop-PK) model for busulfan in Chinese pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and then estimate busulfan exposure and 2) explore the association between busulfan exposure and clinical outcomes.Methods: A total of 128 patients with 467 busulfan concentrations were obtained for Pop-PK modeling using nonlinear mixed effect model (NONMEM) software. Sixty-three patients who received the 16-dose busulfan conditioning regimen were enrolled to explore the correlations between clinical outcomes and the busulfan area under the concentration–time curve (AUC) using the Cox proportional hazards regression model, Kaplan–Meier method and logistic regression.Results: The typical values for clearance (CL) and distribution volume (V) of busulfan were 7.71 L h−1 and 42.4 L, respectively. The allometric normal fat mass (NFM) and maturation function (Fmat) can be used to describe the variability in CL, and the fat-free mass (FFM) can be used to describe the variability in V. Patients with AUCs of 950–1,600 µM × min had 83.7% (95% CI: 73.3–95.5) event-free survival (EFS) compared with 55.0% (95% CI: 37.0–81.8) for patients with low or high exposure (p = 0.024). The logistic regression analysis results showed no association between transplant-related toxicities and the busulfan AUC (p > 0.05).Conclusions: The variability in busulfan CL was related to the NFM and Fmat, while busulfan V was related to the FFM. Preliminary analysis results suggested that a busulfan AUC of 950–1,600 µM × min was associated with better EFS in children receiving the 16-dose busulfan regimen. |
| first_indexed | 2024-04-12T13:46:59Z |
| format | Article |
| id | doaj.art-aa9e45f7ef0f44d3bf22e3ace7fc000c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T13:46:59Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-aa9e45f7ef0f44d3bf22e3ace7fc000c2022-12-22T03:30:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.905879905879The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic StudyXiaohuan Du0Xiaohuan Du1Chenrong Huang2Chenrong Huang3Ling Xue4Ling Xue5Zheng Jiao6Min Zhu7Jie Li8Jun Lu9Peifang Xiao10Xuemei Zhou11Chenmei Mao12Zengyan Zhu13Ji Dong14Xiaoxue Liu15Zhiyao Chen16Shichao Zhang17Yiduo Ding18Shaoyan Hu19Liyan Miao20Liyan Miao21Liyan Miao22Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute for Interdisciplinary Drug Research and Translational Sciences, College of Pharmaceutical Science, Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacology, University of the Basque Country (UPV/EHU), Leioa, SpainDepartment of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Hematology and Oncology, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology and Oncology, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology and Oncology, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology and Oncology, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Hematology and Oncology, The Children’s Hospital of Soochow University, Suzhou, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute for Interdisciplinary Drug Research and Translational Sciences, College of Pharmaceutical Science, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, ChinaAims: The aims of the study were to 1) establish a population pharmacokinetic (Pop-PK) model for busulfan in Chinese pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and then estimate busulfan exposure and 2) explore the association between busulfan exposure and clinical outcomes.Methods: A total of 128 patients with 467 busulfan concentrations were obtained for Pop-PK modeling using nonlinear mixed effect model (NONMEM) software. Sixty-three patients who received the 16-dose busulfan conditioning regimen were enrolled to explore the correlations between clinical outcomes and the busulfan area under the concentration–time curve (AUC) using the Cox proportional hazards regression model, Kaplan–Meier method and logistic regression.Results: The typical values for clearance (CL) and distribution volume (V) of busulfan were 7.71 L h−1 and 42.4 L, respectively. The allometric normal fat mass (NFM) and maturation function (Fmat) can be used to describe the variability in CL, and the fat-free mass (FFM) can be used to describe the variability in V. Patients with AUCs of 950–1,600 µM × min had 83.7% (95% CI: 73.3–95.5) event-free survival (EFS) compared with 55.0% (95% CI: 37.0–81.8) for patients with low or high exposure (p = 0.024). The logistic regression analysis results showed no association between transplant-related toxicities and the busulfan AUC (p > 0.05).Conclusions: The variability in busulfan CL was related to the NFM and Fmat, while busulfan V was related to the FFM. Preliminary analysis results suggested that a busulfan AUC of 950–1,600 µM × min was associated with better EFS in children receiving the 16-dose busulfan regimen.https://www.frontiersin.org/articles/10.3389/fphar.2022.905879/fullevent-free survivalbusulfan exposurepopulation pharmacokineticspediatric patientshematopoietic stem cell transplantation |
| spellingShingle | Xiaohuan Du Xiaohuan Du Chenrong Huang Chenrong Huang Ling Xue Ling Xue Zheng Jiao Min Zhu Jie Li Jun Lu Peifang Xiao Xuemei Zhou Chenmei Mao Zengyan Zhu Ji Dong Xiaoxue Liu Zhiyao Chen Shichao Zhang Yiduo Ding Shaoyan Hu Liyan Miao Liyan Miao Liyan Miao The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study Frontiers in Pharmacology event-free survival busulfan exposure population pharmacokinetics pediatric patients hematopoietic stem cell transplantation |
| title | The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study |
| title_full | The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study |
| title_fullStr | The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study |
| title_full_unstemmed | The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study |
| title_short | The Correlation Between Busulfan Exposure and Clinical Outcomes in Chinese Pediatric Patients: A Population Pharmacokinetic Study |
| title_sort | correlation between busulfan exposure and clinical outcomes in chinese pediatric patients a population pharmacokinetic study |
| topic | event-free survival busulfan exposure population pharmacokinetics pediatric patients hematopoietic stem cell transplantation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.905879/full |
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