Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients

T. Minematsu, E. Sugiyama, M. Kusama, Satoko Hori, Y. Yamada, Hisakazu Ohtani, Y. Sawada, H. Sato, T. Takayama, Y. Sugawara, M. Makuuchi, T. Iga

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objective Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. Methods First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. Results In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation of Hct with the ratio of dose/trough concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). Conclusion Hct may be an important factor affecting the pharmacokinetics of FK506 in living donor liver transplantation recipients. It may be necessary to take Hct into consideration in the FK506 dosing regimen, especially when the Hct is low.

Original languageEnglish
Pages (from-to)1506-1511
Number of pages6
JournalTransplantation Proceedings
Volume36
Issue number5
DOIs
Publication statusPublished - 2004 Jun
Externally publishedYes

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Living Donors
Tacrolimus
Hematocrit
Pharmacokinetics
Liver
Dilatation and Curettage
Blood Cells
Transplant Recipients
Liver Transplantation

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients. / Minematsu, T.; Sugiyama, E.; Kusama, M.; Hori, Satoko; Yamada, Y.; Ohtani, Hisakazu; Sawada, Y.; Sato, H.; Takayama, T.; Sugawara, Y.; Makuuchi, M.; Iga, T.

In: Transplantation Proceedings, Vol. 36, No. 5, 06.2004, p. 1506-1511.

Research output: Contribution to journalArticle

Minematsu, T, Sugiyama, E, Kusama, M, Hori, S, Yamada, Y, Ohtani, H, Sawada, Y, Sato, H, Takayama, T, Sugawara, Y, Makuuchi, M & Iga, T 2004, 'Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients', Transplantation Proceedings, vol. 36, no. 5, pp. 1506-1511. https://doi.org/10.1016/j.transproceed.2004.04.097
Minematsu, T. ; Sugiyama, E. ; Kusama, M. ; Hori, Satoko ; Yamada, Y. ; Ohtani, Hisakazu ; Sawada, Y. ; Sato, H. ; Takayama, T. ; Sugawara, Y. ; Makuuchi, M. ; Iga, T. / Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients. In: Transplantation Proceedings. 2004 ; Vol. 36, No. 5. pp. 1506-1511.
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T1 - Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients

AU - Minematsu, T.

AU - Sugiyama, E.

AU - Kusama, M.

AU - Hori, Satoko

AU - Yamada, Y.

AU - Ohtani, Hisakazu

AU - Sawada, Y.

AU - Sato, H.

AU - Takayama, T.

AU - Sugawara, Y.

AU - Makuuchi, M.

AU - Iga, T.

PY - 2004/6

Y1 - 2004/6

N2 - Objective Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. Methods First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. Results In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation of Hct with the ratio of dose/trough concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). Conclusion Hct may be an important factor affecting the pharmacokinetics of FK506 in living donor liver transplantation recipients. It may be necessary to take Hct into consideration in the FK506 dosing regimen, especially when the Hct is low.

AB - Objective Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. Methods First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. Results In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation of Hct with the ratio of dose/trough concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). Conclusion Hct may be an important factor affecting the pharmacokinetics of FK506 in living donor liver transplantation recipients. It may be necessary to take Hct into consideration in the FK506 dosing regimen, especially when the Hct is low.

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DO - 10.1016/j.transproceed.2004.04.097

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JF - Transplantation Proceedings

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