Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation

Ikuko Yano, Satohiro Masuda, Hiroto Egawa, Mitsuhiro Sugimoto, Masahide Fukudo, Yuko Yoshida, Sachiyo Hashi, Atsushi Yoshizawa, Yasuhiro Ogura, Kohei Ogawa, Akira Mori, Toshimi Kaido, Shinji Uemoto, Ken Ichi Inui

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Abstract

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.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume68
Issue number3
DOIs
Publication statusPublished - Mar 1 2012

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Calcineurin
Living Donors
Tacrolimus
Liver Transplantation
Transplantation
Area Under Curve
Blood Cells
Oral Administration
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. / Yano, Ikuko; Masuda, Satohiro; Egawa, Hiroto; Sugimoto, Mitsuhiro; Fukudo, Masahide; Yoshida, Yuko; Hashi, Sachiyo; Yoshizawa, Atsushi; Ogura, Yasuhiro; Ogawa, Kohei; Mori, Akira; Kaido, Toshimi; Uemoto, Shinji; Inui, Ken Ichi.

In: European Journal of Clinical Pharmacology, Vol. 68, No. 3, 01.03.2012, p. 259-266.

Research output: Contribution to journalArticle

Yano, I, Masuda, S, Egawa, H, Sugimoto, M, Fukudo, M, Yoshida, Y, Hashi, S, Yoshizawa, A, Ogura, Y, Ogawa, K, Mori, A, Kaido, T, Uemoto, S & Inui, KI 2012, 'Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation', European Journal of Clinical Pharmacology, vol. 68, no. 3, pp. 259-266. https://doi.org/10.1007/s00228-011-1129-x
Yano, Ikuko ; Masuda, Satohiro ; Egawa, Hiroto ; Sugimoto, Mitsuhiro ; Fukudo, Masahide ; Yoshida, Yuko ; Hashi, Sachiyo ; Yoshizawa, Atsushi ; Ogura, Yasuhiro ; Ogawa, Kohei ; Mori, Akira ; Kaido, Toshimi ; Uemoto, Shinji ; Inui, Ken Ichi. / Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. In: European Journal of Clinical Pharmacology. 2012 ; Vol. 68, No. 3. pp. 259-266.
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AU - Yano, Ikuko

AU - Masuda, Satohiro

AU - Egawa, Hiroto

AU - Sugimoto, Mitsuhiro

AU - Fukudo, Masahide

AU - Yoshida, Yuko

AU - Hashi, Sachiyo

AU - Yoshizawa, Atsushi

AU - Ogura, Yasuhiro

AU - Ogawa, Kohei

AU - Mori, Akira

AU - Kaido, Toshimi

AU - Uemoto, Shinji

AU - Inui, Ken Ichi

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N2 - 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.

AB - 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.

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