Population pharmacokinetics of tacrolimus in umbilical cord blood transplant patients focusing on the variation in red blood cell counts

What is known and objective The distribution of tacrolimus (TAC), an immunosuppressant used during cord blood transplantation (CBT)—one of the haematopoietic stem cell transplantations, to red blood cell (RBC) is approximately 90% in whole blood. In CBT patients, the total RBC count shows dramatic f...

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Bibliographic Details
Published in:Journal of clinical pharmacy and therapeutics 2021-02, Vol.46 (1), p.190-197
Main Authors: Yoshida, Saki, Fujimoto, Ayumi, Fukushima, Keizo, Ando, Motozumi, Irie, Kei, Hirano, Tatsuya, Miyasaka, Moena, Shimomura, Yoshimitsu, Ishikawa, Takayuki, Ikesue, Hiroaki, Muroi, Nobuyuki, Hashida, Tohru, Sugioka, Nobuyuki
Format: Article
Language:English
Subjects:
Antitumor agents
Blood
Blood levels
Cord blood
Erythrocytes
haematopoietic stem cell transplantation
Hematopoietic stem cells
Hemoglobin
Pharmacokinetics
population pharmacokinetics
Radiation
Tacrolimus
Therapeutic drug monitoring
Transplantation
Transplants & implants
Umbilical cord
umbilical cord blood transplantation
Variation
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Summary:What is known and objective The distribution of tacrolimus (TAC), an immunosuppressant used during cord blood transplantation (CBT)—one of the haematopoietic stem cell transplantations, to red blood cell (RBC) is approximately 90% in whole blood. In CBT patients, the total RBC count shows dramatic fluctuation due to conditioning before transplantation, including anticancer agents and total body irradiation, as well as RBC transfusions during the treatment period. Therefore, the amount of TAC in whole blood may show wide variation. However, therapeutic drug monitoring (TDM) of TAC has been performed based on the whole blood concentration. In this study, to contribute to TDM of TAC in CBT, we performed the population pharmacokinetic (PPK) analysis of TAC in 56 CBT patients and investigated the factors that affected the concentration of TAC, focusing the variation of RBC count. Method A one‐compartment model was applied to the observed whole blood TAC concentrations, and a PPK analysis was conducted with a non‐linear mixed effect model. Results and discussion Our final PPK model indicated good robustness and accuracy. In addition, haemoglobin (Hb) level was an influential covariate on Vd, which was expressed as Vd(L) = 91.4 × (Hb/8.2)(−1.07). What is new and conclusion In this study, our results showed the necessity for the Hb level monitoring during TDM of TAC in CBT patients and provided useful information for improving TDM strategy of TAC. Therapeutic drug monitoring of tacrolimus in CBT patients needs to monitor the red blood cell count.
ISSN:0269-4727
1365-2710
DOI:10.1111/jcpt.13279