title: Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Minematsu
authors.forename: E
authors.initials: E
authors.lastname: Sugiyama
authors.forename: M
authors.initials: M
authors.lastname: Kusama
authors.forename: S
authors.initials: S
authors.lastname: Hori
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Ohtani
authors.forename: Y
authors.initials: Y
authors.lastname: Sawada
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Takayama
authors.forename: Y
authors.initials: Y
authors.lastname: Sugawara
authors.forename: M
authors.initials: M
authors.lastname: Makuuchi
authors.forename: T
authors.initials: T
authors.lastname: Iga
mesh_terms: D000328:Adult; D016903:Drug Monitoring / Q000379:methods; D006400:Hematocrit; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics; D007700:Kinetics; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D019520:Living Donors; D008657:Metabolic Clearance Rate; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus