The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony pharmacokinetic substudy

Josep M. Grinyo, Henrik Ekberg, Richard D. Mamelok, Federico Oppenheimer, Jaime Sanchez-Plumed, Miguel Angel Gentil, Domingo Hernandez, Dirk R. Kuypers, Merce Brunet

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Methods. A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal transplant patients received standard-dose cyclosporine, MMF 2 g/day and corticosteroids, or daclizumab induction, MMF 2 g/day and corticosteroids plus low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus. The area under the concentration-time curve (AUC(0-12)) of MPA and its metabolites between treatment groups was compared. Pharmacokinetic sampling was performed before MMF administration and at 20, 40, 75 min; 2, 3, 6, 8, 10 and 12 h post-dose on Day 7 and Months 1 and 3. Results. Compared with standard-dose cyclosporine, patients receiving low-dose tacrolimus or low-dose sirolimus had significantly higher AUC(0-12) values for MPA at Day 7 and Month 1 and for free MPA at Day 7, and significantly lower AUC(0-12) values for 7-O-MPA-glucuronide (MPAG) at Month 1 and for acyl-glucuronide at Months 1 and 3 (P < 0.05). AUC(0-12) of MPA and free MPA was significantly greater with low-dose tacrolimus and low-dose sirolimus than with low-dose cyclosporine in the first month (P < 0.05). The ratio of MPA to MPAG exposure was significantly higher in the three low-dose groups than in the standard-dose cyclosporine group (P < 0.05). Conclusions. Standard- and low-dose cyclosporine reduces the exposure of MPA and free MPA compared to low-dose tacrolimus or low-dose sirolimus in patients given the same dose of MMF.
    Original languageEnglish
    Pages (from-to)2269-2276
    JournalNephrology Dialysis Transplantation
    Volume24
    Issue number7
    DOIs
    Publication statusPublished - 2009

    Subject classification (UKÄ)

    • Urology and Nephrology

    Free keywords

    • mycophenolate mofetil
    • mycophenolic acid
    • glucuronide
    • renal transplantation
    • pharmacokinetics

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