title: Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation.
abstract: OBJECTIVE
  Tacrolimus pharmacokinetics and calcineurin activity in peripheral blood mononuclear cells (PBMCs) were investigated in adult patients undergoing primary living-donor liver transplantation (LDLT) in order to clarify the significance of monitoring the tacrolimus blood trough concentration during the early post-transplantation period.
  
  
  METHODS
  Fourteen patients were enrolled in this study, and time-course data following the oral administration of a conventional tacrolimus formulation twice daily were obtained at 1 and 3 weeks post-transplantation. The concentration of tacrolimus in whole blood and calcineurin activity in PBMCs were measured.
  
  
  RESULTS
  The apparent clearance of tacrolimus significantly increased at 3 weeks versus 1 week post-transplantation, although the trough concentration did not significantly differ at these time points. The concentration at each sampling time, except at 1 h post-dose, correlated well with the area under the concentration-time curve from 0 to 12 h (AUC(0-12)). Neither the concentration at the trough time point nor AUC(0-12) was correlated with the area under the calcineurin activity-time curve from 0 to 12 h; however, calcineurin activity at the trough time point was strongly correlated with the latter (r                            (2) > 0.92).
  
  
  CONCLUSIONS
  Based on these results, trough concentration monitoring can be considered an appropriate procedure for routine tacrolimus dosage adjustment in adult LDLT patients. Monitoring of calcineurin activity at the trough time point was also found to be potentially useful for predicting the immunological status of the patient during the tacrolimus dosing interval.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital, Kyoto University, Kyoto, Japan. iyano@kuhp.kyoto-u.ac.jp
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yano
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Hiroto
authors.initials: H
authors.lastname: Egawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Fukudo
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Hashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogura
authors.forename: Kohei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Akira
authors.initials: A
authors.lastname: Mori
authors.forename: Toshimi
authors.initials: T
authors.lastname: Kaido
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D019540:Area Under Curve; D019703:Calcineurin / Q000097:blood*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D019703:Calcineurin; D016559:Tacrolimus