Korean J Clin Pharm.  2020 Mar;30(1):36-43. 10.24304/kjcp.2020.30.1.36.

The Effects of Intrapatient Variability in Tacrolimus Concentration on Clinical Outcomes Immediately After Liver Transplantation

Affiliations
  • 1Department of Pharmacy, Seoul National University Bundang Hospital, Gyeonggi-do 13620, Republic of Korea
  • 2Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei Unversity, Incheon 21983, Republic of Korea
  • 3Department of Surgery, Seoul National University College of Medicine & Seoul National University Bundang Hospital, Gyeonggi-do 13620, Republic of Korea
  • 4College of Pharmacy & Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Republic of Korea
  • 5Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea

Abstract

Background
Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used in post-transplantation maintenance therapy. The drug has a narrow therapeutic range and requires periodic therapeutic drug monitoring. Although many studies have reported the effects of intrapatient variability of tacrolimus on survival, rejection, and complications in renal transplant recipients, very few studies have reported these effects in liver transplant recipients. The purpose of this study was to evaluate the effect of intrapatient variability of tacrolimus on clinical outcomes after liver transplantation.
Methods
Intrapatient variability was calculated using individual, averaged tacrolimus concentrations. Patients were divided into two groups according to their median variability value: high-variability and low-variability groups. The rate of deviation from the therapeutic range, incidence of acute rejection, posttransplant diabetes, incidence of infection, and estimated glomerular filtration rate (eGFR) after transplantation were compared between the groups.
Results
Of the total patients (n=82), the high-variability group (n=41) exhibited significantly greater deviation from the therapeutic range (65.92% vs. 56.84%; p<0.001). There was no significant difference in acute rejection or posttransplantation diabetes incidence or eGFR; however, the number of infection in the first 6 months was significantly lower in the low-variability group (0.4 vs. 0.9 times; p=0.039). Multiple linear regression analysis showed that the number of infection significantly increased as intrapatient variability increased (p=0.015).
Conclusion
High intrapatient variability in tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection.

Keyword

Tacrolimus; liver transplantation; intrapatient variability; graft rejection; infections
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