title: Cyclosporine concentration-dependent increase in concentration ratio of mycophenolic acid acyl and phenol glucuronides to mycophenolic acid in stable kidney transplant recipients.
abstract: OBJECTIVE
  The aim of this study was to evaluate the influence of cyclosporine (CyA) and tacrolimus (Tac) on the pharmacokinetics of mycophenolic acid (MPA) and its glucuronides.
  
  
  METHODS
  Kidney transplant recipients treated with mycophenolate mofetil and CyA (n=18) or Tac (n=17) in the stable phase were enrolled. The dependence of the trough concentration (C(0)) ratios of MPA acyl glucuronide (AcMPAG) to MPA (AcMPAG/MPA) and MPA phenol glucuronide (MPAG) to MPA (MPAG/MPA) on CyA C(0) or Tac C(0) was evaluated.
  
  
  RESULTS
  AcMPAG C(0) and MPAG C(0) were significantly higher in CyA- than Tac-treated recipients (P=0.04 and 0.02, respectively). AcMPAG/MPA and MPAG/MPA were significantly correlated to CyA C(0) (r=0.75, P<0.01 and r=0.81, P<0.01, respectively), but not to Tac C(0).
  
  
  CONCLUSIONS
  CyA increased AcMPAG/MPA as well as MPAG/MPA in a concentration-dependent manner, suggesting that higher CyA may cause AcMPAG-related adverse reactions. Tac did not alter pharmacokinetics of MPA and its glucuronides.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ushiyama
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: D000293:Adolescent; D000328:Adult; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D020719:Glucuronides / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus