Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics
ABSTRACT: Objectives: Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distr...
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Elsevier
2025-01-01
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| Series: | Current Therapeutic Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0011393X24000456 |
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| author | Haruno Oku, BS Saki Yoshida, BS Takumi Hotta, BS Hirohito Muroi, BS Keizo Fukushima, PhD Kei Irie, PhD Tatsuya Hirano, BS Yoshimitsu Shimomura, MD Takayuki Ishikawa, MD, PhD Hiroaki Ikesue, PhD Nobuyuki Muroi, PhD Tohru Hashida, PhD Nobuyuki Sugioka, PhD |
| author_facet | Haruno Oku, BS Saki Yoshida, BS Takumi Hotta, BS Hirohito Muroi, BS Keizo Fukushima, PhD Kei Irie, PhD Tatsuya Hirano, BS Yoshimitsu Shimomura, MD Takayuki Ishikawa, MD, PhD Hiroaki Ikesue, PhD Nobuyuki Muroi, PhD Tohru Hashida, PhD Nobuyuki Sugioka, PhD |
| author_sort | Haruno Oku, BS |
| collection | DOAJ |
| description | ABSTRACT: Objectives: Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distribution of tacrolimus and hemoglobin levels, which reflect the red blood cell (RBC) count. In this study, we evaluated the influence of the conditioning regimen (myeloablative and reduced-intensity conditioning) or donor source (cord blood, bone marrow, and peripheral blood stem cells) on the pharmacokinetics of tacrolimus in patients undergoing HSCT, including those undergoing CBT. We also examined applicability of dosing strategy of tacrolimus considering the RBC count. Methods: We retrospectively analyzed clinical data—including whole-blood tacrolimus concentrations—from patients with HSCT. The observation period spanned from first continuous intravenous infusions until switch to oral medication, transfer to another hospital, relapse, or death. Population pharmacokinetic analysis was performed on whole-blood tacrolimus concentrations obtained from therapeutic drug monitoring during the observation period. Patient characteristics and laboratory data were evaluated as covariates. Results: We enrolled 91 patients undergoing HSCT (CBT: n = 56; bone marrow transplantation: n = 22; and peripheral blood stem cell transplantation: n = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (n = 1,658 measurements) using a one-compartment and additive error model. The conditioning regimen and donor source did not have an impact on the pharmacokinetics of tacrolimus. Therefore, these factors were not considered when forming the dosing strategy. Nevertheless, a negative correlation between volume of distribution and hemoglobin level was confirmed, indicating that monitoring the RBC count is useful in assessing the dosing strategy. Conclusions: A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT. |
| format | Article |
| id | doaj-art-8a677e24609749f4816283c153db99b1 |
| institution | Kabale University |
| issn | 0011-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Therapeutic Research |
| spelling | doaj-art-8a677e24609749f4816283c153db99b12025-01-22T05:40:03ZengElsevierCurrent Therapeutic Research0011-393X2025-01-01102100775Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus PharmacokineticsHaruno Oku, BS0Saki Yoshida, BS1Takumi Hotta, BS2Hirohito Muroi, BS3Keizo Fukushima, PhD4Kei Irie, PhD5Tatsuya Hirano, BS6Yoshimitsu Shimomura, MD7Takayuki Ishikawa, MD, PhD8Hiroaki Ikesue, PhD9Nobuyuki Muroi, PhD10Tohru Hashida, PhD11Nobuyuki Sugioka, PhD12Department of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, JapanDepartment of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, Japan; Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, JapanDepartment of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan; Department of Medical Cooperation, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, JapanDepartment of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Hematology, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Hematology, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, JapanDepartment of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan; Department of Medical Cooperation, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, JapanDepartment of Clinical Pharmacokinetics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Hyogo, Japan; Corresponding author.ABSTRACT: Objectives: Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distribution of tacrolimus and hemoglobin levels, which reflect the red blood cell (RBC) count. In this study, we evaluated the influence of the conditioning regimen (myeloablative and reduced-intensity conditioning) or donor source (cord blood, bone marrow, and peripheral blood stem cells) on the pharmacokinetics of tacrolimus in patients undergoing HSCT, including those undergoing CBT. We also examined applicability of dosing strategy of tacrolimus considering the RBC count. Methods: We retrospectively analyzed clinical data—including whole-blood tacrolimus concentrations—from patients with HSCT. The observation period spanned from first continuous intravenous infusions until switch to oral medication, transfer to another hospital, relapse, or death. Population pharmacokinetic analysis was performed on whole-blood tacrolimus concentrations obtained from therapeutic drug monitoring during the observation period. Patient characteristics and laboratory data were evaluated as covariates. Results: We enrolled 91 patients undergoing HSCT (CBT: n = 56; bone marrow transplantation: n = 22; and peripheral blood stem cell transplantation: n = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (n = 1,658 measurements) using a one-compartment and additive error model. The conditioning regimen and donor source did not have an impact on the pharmacokinetics of tacrolimus. Therefore, these factors were not considered when forming the dosing strategy. Nevertheless, a negative correlation between volume of distribution and hemoglobin level was confirmed, indicating that monitoring the RBC count is useful in assessing the dosing strategy. Conclusions: A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT.http://www.sciencedirect.com/science/article/pii/S0011393X24000456hematopoietic stem cell transplantationpopulation pharmacokineticstacrolimustherapeutic drug monitoring |
| spellingShingle | Haruno Oku, BS Saki Yoshida, BS Takumi Hotta, BS Hirohito Muroi, BS Keizo Fukushima, PhD Kei Irie, PhD Tatsuya Hirano, BS Yoshimitsu Shimomura, MD Takayuki Ishikawa, MD, PhD Hiroaki Ikesue, PhD Nobuyuki Muroi, PhD Tohru Hashida, PhD Nobuyuki Sugioka, PhD Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics Current Therapeutic Research hematopoietic stem cell transplantation population pharmacokinetics tacrolimus therapeutic drug monitoring |
| title | Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics |
| title_full | Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics |
| title_fullStr | Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics |
| title_full_unstemmed | Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics |
| title_short | Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics |
| title_sort | effect of hematopoietic stem cell transplantation regimen on tacrolimus pharmacokinetics |
| topic | hematopoietic stem cell transplantation population pharmacokinetics tacrolimus therapeutic drug monitoring |
| url | http://www.sciencedirect.com/science/article/pii/S0011393X24000456 |
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