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Impact of Calcineurin Inhibitors on Urinary Excretion of Mycophenolic Acid and Its Glucuronide in Kidney Transplant Recipients

Authors

  • Dr Takafumi Naito PhD,

    1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu
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  • Dr Yasuaki Mino MS,

    1. Japan Department of Clinical Pharmaceutics and Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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  • Dr Atsushi Otsuka MD, PhD,

    1. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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  • Dr Tomomi Ushiyama MD, PhD,

    1. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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  • Dr Toshiki Ito MD,

    1. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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  • Dr Seiichiro Ozono MD, PhD,

    1. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan
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  • Dr Yoshiyuki Kagawa PhD,

    1. Japan Department of Clinical Pharmaceutics and Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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  • Dr Junichi Kawakami PhD

    Corresponding author
    1. Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu
      Address for correspondence: Junichi Kawakami, PhD, Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1–20-1 Handayama, Hamamatsu 431–3192, Japan; e-mail: kawakami-ham@umin.ac.jp.
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Address for correspondence: Junichi Kawakami, PhD, Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1–20-1 Handayama, Hamamatsu 431–3192, Japan; e-mail: kawakami-ham@umin.ac.jp.

Abstract

Concomitant cyclosporine interacts with mycophenolic acid (MPA) through inhibition of the biliary excretion of its glucuronide (MPAG). The aim of this study was to evaluate the influence of calcineurin inhibitors on the plasma disposition and urinary excretion of MPA and MPAG in kidney transplant recipients. Twelve recipients treated with tacrolimus and 18 treated with cyclosporine at 30 days after transplantation were enrolled. AUC from 0 to 12 hours (AUC0–12) of MPA was significantly higher in tacrolimus-treated than in cyclosporine-treated recipients. In contrast, there was no significant difference in MPAG AUC0–12 between calcineurin inhibitor medications. Unbound fractions of MPA and MPAG did not change significantly in a comparison between the tacrolimus and cyclosporine treatments (0.90% vs 1.27% in MPA; 20.0% vs 19.3% in MPAG). The ratio of renal clearance to creatinine clearance (CLR/CLCr) of MPA was significantly lower in tacrolimus- than in cyclosporine-treated recipients (0.054 vs 0.100). In contrast, no significant difference was observed in the CLR/CLCr of MPAG between the tacrolimus and cyclosporine treatments (0.19 vs 0.18). In conclusion, concomitant calcineurin inhibitors influenced the urinary excretion of MPA but not MPAG in kidney transplant recipients. The results suggest the presence of renal tubular secretion in the urinary excretion process of MPA.

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