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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

Grinyo, Josep M.; Ekberg, Henrik LU ; Mamelok, Richard D.; Oppenheimer, Federico; Sanchez-Plumed, Jaime; Angel Gentil, Miguel; Hernandez, Domingo; Kuypers, Dirk R. and Brunet, Merce (2009) In Nephrology Dialysis Transplantation 24(7). p.2269-2276
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mycophenolate mofetil, mycophenolic acid, glucuronide, renal transplantation, pharmacokinetics
in
Nephrology Dialysis Transplantation
volume
24
issue
7
pages
2269 - 2276
publisher
Oxford University Press
external identifiers
  • wos:000267226500044
  • scopus:67651115805
ISSN
1460-2385
DOI
10.1093/ndt/gfp162
language
English
LU publication?
yes
id
63c97df6-5ae8-4eb8-8261-af4f6bcc8f09 (old id 1441202)
date added to LUP
2009-07-28 11:05:56
date last changed
2017-12-10 04:04:56
@article{63c97df6-5ae8-4eb8-8261-af4f6bcc8f09,
  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 &lt; 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 &lt; 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 &lt; 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.},
  author       = {Grinyo, Josep M. and Ekberg, Henrik and Mamelok, Richard D. and Oppenheimer, Federico and Sanchez-Plumed, Jaime and Angel Gentil, Miguel and Hernandez, Domingo and Kuypers, Dirk R. and Brunet, Merce},
  issn         = {1460-2385},
  keyword      = {mycophenolate mofetil,mycophenolic acid,glucuronide,renal transplantation,pharmacokinetics},
  language     = {eng},
  number       = {7},
  pages        = {2269--2276},
  publisher    = {Oxford University Press},
  series       = {Nephrology Dialysis Transplantation},
  title        = {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},
  url          = {http://dx.doi.org/10.1093/ndt/gfp162},
  volume       = {24},
  year         = {2009},
}