The Impact of Total Bilirubin on Plasma Micafungin Levels in Living-Donor Liver Transplantation Recipients with Severe Liver Dysfunction

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  • Muraki Yuichi
    Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University
  • Iwamoto Takuya
    Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University
  • Kagawa Yoshiyuki
    Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmaceutical Sciences University of Shizuoka
  • Sakurai Hiroyuki
    Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine
  • Usui Masanobu
    Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine
  • Isaji Shuji
    Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine
  • Uemoto Shinji
    Department of Transplantation and Immunology, Kyoto University Graduate School of Medicine
  • Okuda Masahiro
    Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University

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The objective of this study was to propose a clinically effective and safe micafungin (MCFG) treatment for 20 recipients of living-donor liver transplantations (LDLTs), after considering the influence of liver function on its plasma pharmacokinetics. In all patients, an improvement of clinical symptoms was observed after MCFG treatment. Liver and renal functions were not significantly changed by the administration of MCFG. In the recipients, the trough plasma concentration of MCFG was 5.2±2.6μg/ml (mean±S.D.), which was dependent on the dose (p=0.0033). Additionally, there was a good correlation between the trough and peak MCFG plasma concentrations (p<0.0001). The trough concentration of MCFG was significantly correlated with serum total bilirubin levels (p=0.0166). In addition, the MCFG concentration/dose (C/D) ratio was significantly higher in the patients with total bilirubin levels >5 mg/dl than in those with total bilirubin levels ≤5 mg/dl (p<0.0001). The C/D ratio of MCFG was weakly but not significantly correlated with total bilirubin levels at total bilirubin levels >5 mg/dl (p=0.0508). Therefore, a reduced dose of MCFG should be considered when total bilirubin levels are >5 mg/dl. Furthermore, careful monitoring of total bilirubin levels is recommended during MCFG treatment in LDLT-recipients with severe liver dysfunction. These results provide helpful advice about MCFG administration for the treatment of fungal infections in LDLT patients with fluctuating liver function.

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