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

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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 (AUC0–12). Neither the concentration at the trough time point nor AUC0–12 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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Acknowledgments

The authors would like to thank Junichi Nomura, Takashi Ikoma, and Ikuo Sekiguchi for their kind assistance. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Author notes

  1. Hiroto Egawa

    Present address: Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, Japan

  2. Ken-ichi Inui

    Present address: Kyoto Pharmaceutical University, Kyoto, Japan

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Medicine, Kyoto University Hospital, Kyoto University, Kyoto, Japan

    Ikuko Yano, Satohiro Masuda, Mitsuhiro Sugimoto, Masahide Fukudo, Yuko Yoshida, Sachiyo Hashi & Ken-ichi Inui

  2. Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Ikuko Yano

  3. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Hiroto Egawa, Atsushi Yoshizawa, Yasuhiro Ogura, Kohei Ogawa, Akira Mori, Toshimi Kaido & Shinji Uemoto

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  1. Ikuko Yano
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Correspondence to Ikuko Yano.

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Yano, I., Masuda, S., Egawa, H. et al. Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation. Eur J Clin Pharmacol 68, 259–266 (2012). https://doi.org/10.1007/s00228-011-1129-x

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  • DOI: https://doi.org/10.1007/s00228-011-1129-x

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