Cyclosporine concentration-dependent increase in concentration ratio of mycophenolic acid acyl and phenol glucuronides to mycophenolic acid in stable kidney transplant recipients.
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.
Mino
Yasuaki
Y
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Naito
Takafumi
T
Otsuka
Atsushi
A
Ushiyama
Tomomi
T
Ozono
Seiichiro
S
Kagawa
Yoshiyuki
Y
Kawakami
Junichi
J
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
D020719:Glucuronides; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus