Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting
ABSTRACT Granulocyte colony‐stimulating factor (G‐CSF) mobilizes peripheral blood (PB) progenitor cells from bone marrow (BM) into circulation for PB stem cell transplantation (PBSCT). This study aimed to develop a population pharmacokinetic–pharmacodynamic (PK‐PD) model of filgrastim in healthy sub...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70121 |
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| author | Xu Jiang Jun Seok Cha Byung Hak Jin Choon Ok Kim Dongwoo Chae |
| author_facet | Xu Jiang Jun Seok Cha Byung Hak Jin Choon Ok Kim Dongwoo Chae |
| author_sort | Xu Jiang |
| collection | DOAJ |
| description | ABSTRACT Granulocyte colony‐stimulating factor (G‐CSF) mobilizes peripheral blood (PB) progenitor cells from bone marrow (BM) into circulation for PB stem cell transplantation (PBSCT). This study aimed to develop a population pharmacokinetic–pharmacodynamic (PK‐PD) model of filgrastim in healthy subjects to optimize PB CD34+ cell collection. Plasma filgrastim concentrations and CD34+ cell count data were obtained from a clinical study involving healthy Korean subjects. A total of 1378 plasma concentration measurements and 982 CD34+ cell count data collected from 53 subjects were used in the PK‐PD model. Filgrastim PKs were adequately described by a one‐compartment linear disposition model with an additional transit compartment for absorption. Log‐transformed body weight was the only significant covariate affecting the volume of distribution and clearance. CD34+ cell mobilization was best captured by a modified Friberg model, assuming continual entry of proliferating BM stem cells into PB via a single transit compartment. Simulation results suggested that the 5 μg/kg twice‐daily dosing regimen may yield higher CD34+ cell counts compared to the 10 μg/kg once‐daily regimen for achieving target CD34+ cell counts of 20/μL and 50/μL. We successfully developed a robust PK‐PD model of G‐CSF that optimizes the yield of CD34+ cells during allogeneic PBSCT. This model can guide the efficient determination of optimal G‐CSF dosing regimens and CD34+ cell harvesting strategies. |
| format | Article |
| id | doaj-art-8fca3bc47468440d8bfcbeb9dd26c206 |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-8fca3bc47468440d8bfcbeb9dd26c2062025-01-24T08:17:46ZengWileyClinical and Translational Science1752-80541752-80622025-01-01181n/an/a10.1111/cts.70121Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell HarvestingXu Jiang0Jun Seok Cha1Byung Hak Jin2Choon Ok Kim3Dongwoo Chae4Department of Pharmacology Yonsei University College of Medicine Seoul KoreaDepartment of Pharmacology Yonsei University College of Medicine Seoul KoreaDepartment of Clinical Pharmacology, Severance Hospital Yonsei University College of Medicine Seoul KoreaDepartment of Clinical Pharmacology, Severance Hospital Yonsei University College of Medicine Seoul KoreaDepartment of Pharmacology Yonsei University College of Medicine Seoul KoreaABSTRACT Granulocyte colony‐stimulating factor (G‐CSF) mobilizes peripheral blood (PB) progenitor cells from bone marrow (BM) into circulation for PB stem cell transplantation (PBSCT). This study aimed to develop a population pharmacokinetic–pharmacodynamic (PK‐PD) model of filgrastim in healthy subjects to optimize PB CD34+ cell collection. Plasma filgrastim concentrations and CD34+ cell count data were obtained from a clinical study involving healthy Korean subjects. A total of 1378 plasma concentration measurements and 982 CD34+ cell count data collected from 53 subjects were used in the PK‐PD model. Filgrastim PKs were adequately described by a one‐compartment linear disposition model with an additional transit compartment for absorption. Log‐transformed body weight was the only significant covariate affecting the volume of distribution and clearance. CD34+ cell mobilization was best captured by a modified Friberg model, assuming continual entry of proliferating BM stem cells into PB via a single transit compartment. Simulation results suggested that the 5 μg/kg twice‐daily dosing regimen may yield higher CD34+ cell counts compared to the 10 μg/kg once‐daily regimen for achieving target CD34+ cell counts of 20/μL and 50/μL. We successfully developed a robust PK‐PD model of G‐CSF that optimizes the yield of CD34+ cells during allogeneic PBSCT. This model can guide the efficient determination of optimal G‐CSF dosing regimens and CD34+ cell harvesting strategies.https://doi.org/10.1111/cts.70121CD34+filgrastimgranulocyte colony‐stimulating factorpopulation pharmacokinetic‐pharmacodynamic modeling |
| spellingShingle | Xu Jiang Jun Seok Cha Byung Hak Jin Choon Ok Kim Dongwoo Chae Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting Clinical and Translational Science CD34+ filgrastim granulocyte colony‐stimulating factor population pharmacokinetic‐pharmacodynamic modeling |
| title | Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting |
| title_full | Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting |
| title_fullStr | Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting |
| title_full_unstemmed | Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting |
| title_short | Population Pharmacokinetic–Pharmacodynamic Modeling of Granulocyte Colony‐Stimulating Factor to Optimize Dosing and Timing for CD34+ Cell Harvesting |
| title_sort | population pharmacokinetic pharmacodynamic modeling of granulocyte colony stimulating factor to optimize dosing and timing for cd34 cell harvesting |
| topic | CD34+ filgrastim granulocyte colony‐stimulating factor population pharmacokinetic‐pharmacodynamic modeling |
| url | https://doi.org/10.1111/cts.70121 |
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