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

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.

Ekberg, HenrikLund University,Lunds universitet,Enheten för forskning kring njurfunktion och njursjukdom,Kirurgi,Forskargrupper vid Lunds universitet,Renal Research Unit,Surgery,Lund University Research Groups(Swepub:lu)kir-hek (author)
Mamelok, Richard D. (author)
Oppenheimer, Federico (author)
Sanchez-Plumed, Jaime (author)
Angel Gentil, Miguel (author)
Hernandez, Domingo (author)
Kuypers, Dirk R. (author)
Brunet, Merce (author)
Enheten för forskning kring njurfunktion och njursjukdomKirurgi (creator_code:org_t)

In:Nephrology Dialysis Transplantation: Oxford University Press (OUP)24:7, s. 2269-22761460-23850931-0509

By the author/editor: Grinyo, Josep M.; Ekberg, Henrik; Mamelok, Richard ...; Oppenheimer, Fed ...; Sanchez-Plumed, ...; Angel Gentil, Mi ...; show more...; Hernandez, Domin ...; Kuypers, Dirk R.; Brunet, Merce; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

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