PURPOSE: 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.
PURPOSE: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: S Fukatsu; I Yano; T Igarashi; T Hashida; K Takayanagi; H Saito; S Uemoto; T Kiuchi; K Tanaka; K Inui; K Tanaka; K Inui Journal: Eur J Clin Pharmacol Date: 2001-09 Impact factor: 2.953
Authors: Eduard M Scholten; Serge C L M Cremers; Rik C Schoemaker; Ajda T Rowshani; Erik J van Kan; Jan den Hartigh; Leendert C Paul; Johan W de Fijter Journal: Kidney Int Date: 2005-06 Impact factor: 10.612
Authors: R Venkataramanan; A Swaminathan; T Prasad; A Jain; S Zuckerman; V Warty; J McMichael; J Lever; G Burckart; T Starzl Journal: Clin Pharmacokinet Date: 1995-12 Impact factor: 6.447
Authors: Z Wlodarczyk; J-P Squifflet; M Ostrowski; P Rigotti; S Stefoni; F Citterio; Y Vanrenterghem; B K Krämer; D Abramowicz; F Oppenheimer; F Pietruck; G Russ; C Karpf; N Undre Journal: Am J Transplant Date: 2009-08-14 Impact factor: 8.086
Authors: M Yasuhara; T Hashida; M Toraguchi; Y Hashimoto; M Kimura; K Inui; R Hori; Y Inomata; K Tanaka; Y Yamaoka Journal: Transplant Proc Date: 1995-02 Impact factor: 1.066