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http://dx.doi.org/10.24304/kjcp.2020.30.1.36

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

Kim, Eunji (Department of Pharmacy, Seoul National University Bundang Hospital)
Kim, Boram (Department of Pharmacy, Seoul National University Bundang Hospital)
Cho, Jungwon (Department of Pharmacy, Seoul National University Bundang Hospital)
Lee, Jung Hwa (Department of Pharmacy, Seoul National University Bundang Hospital)
Lee, Eunsook (Department of Pharmacy, Seoul National University Bundang Hospital)
Yu, Yun Mi (Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei Unversity)
Cho, Jai Young (Department of Surgery, Seoul National University College of Medicine & Seoul National University Bundang Hospital)
Lee, Euni (College of Pharmacy & Research Institute of Pharmaceutical Science, Seoul National University)
Choi, YoungRok (Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital)
Publication Information
Korean Journal of Clinical Pharmacy / v.30, no.1, 2020 , pp. 36-43 More about this Journal
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, post-transplant 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 post-transplantation 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.
Keywords
Tacrolimus; liver transplantation; intrapatient variability; graft rejection; infections;
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