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- Title
Impact of Calcineurin Inhibitors on Urinary Excretion of Mycophenolic Acid and Its Glucuronide in Kidney Transplant Recipients.
- Authors
Naito, Takafumi; Mino, Yasuaki; Otsuka, Atsushi; Ushiyama, Tomomi; Ito, Toshiki; Ozono, Seiichiro; Kagawa, Yoshiyuki; Kawakami, Junichi
- 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.
- Subjects
MYCOPHENOLIC acid; TACROLIMUS; CYCLOSPORINE; KIDNEY transplant patients; URINALYSIS
- Publication
Journal of Clinical Pharmacology, 2010, Vol 50, Issue 6, p710
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1177/0091270009335003