title: Impact of calcineurin inhibitors on urinary excretion of mycophenolic acid and its glucuronide in kidney transplant recipients.
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 (AUC(0-12)) of MPA was significantly higher in tacrolimus-treated than in cyclosporine-treated recipients. In contrast, there was no significant difference in MPAG AUC(0-12) 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 (CL(R)/CL(Cr)) of MPA was significantly lower in tacrolimusthan in cyclosporine-treated recipients (0.054 vs 0.100). In contrast, no significant difference was observed in the CL(R)/CL(Cr) 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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ushiyama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Ito
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004764:Enterohepatic Circulation; D004791:Enzyme Inhibitors / Q000097:blood / Q000652:urine*; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000652:urine*; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000652:urine*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine*; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus