Influence of metal cations on plasma trough concentration of mycophenolic Acid and its glucuronide in tacrolimus-treated and cyclosporine-treated kidney transplant recipients.
The aim of this study was to evaluate the plasma trough concentrations (C(0)) of mycophenolic acid (MPA) and its major metabolite MPA 7-O-glucuronide (MPAG) in metal cation (MC)(-) (non-treated) and MC(+) (co-treated) patients who received tacrolimus (Tac) or cyclosporine (CyA). Fifty-nine Japanese stable kidney transplant recipients receiving immunosuppressive regimens containing mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI) were included in this study. Seven in the 25 patients receiving Tac and 8 in the 34 patients receiving CyA were treated with concomitant MCs administration. Multiple regression analysis revealed that concomitant MCs and CyA administration influenced MPA C(0). Their standardized partial regression coefficients were -0.29 and -0.41, respectively. Stratified analysis based on CNI treatment revealed that MPA C(0) decreased significantly by 56% with concomitant MCs administration in Tac-treated patients. There was no significant difference in MPA C(0) between the MC(-) and MC(+) groups in CyA-treated patients. With respect to MPAG C(0), MC(+) group tended to be lower by 26% than MC(-) group in Tac-treated patients. There was no significant difference in MPAG C(0) between the MC(-) and MC(+) groups in CyA-treated patients. Concomitant MCs administration did not affect the C(0) ratio of MPAG to MPA in either Tac- or CyA-treated patients. In conclusion, MCs co-administration decrease MPA C(0) in patients receiving Tac and may cause lower MPA exposure. There are little pharmacokinetic interactions between MMF and concomitant MCs in CyA-treated patients.
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Takafumi
T
Naito
Yasuaki
Y
Mino
Atsushi
A
Otsuka
Tomomi
T
Ushiyama
Seiichiro
S
Ozono
Yoshiyuki
Y
Kagawa
Junichi
J
Kawakami
D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008670:Metals / Q000494:pharmacology*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000097:blood* / Q000493:pharmacokinetics; D012044:Regression Analysis; D016559:Tacrolimus / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D020719:Glucuronides; D007166:Immunosuppressive Agents; D008670:Metals; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus