Influence of MRP2 on MPA pharmacokinetics in renal transplant recipients-results of the Pharmacogenomic Substudy within the Symphony Study
(2011) In Nephrology Dialysis Transplantation 26(11). p.3784-3793- Abstract
- Background. The aim of this study was to determine the relationship between single-nucleotide polymorphisms (SNPs) in MRP2 genes and mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients of the Symphony Pharmacogenomic substudy. Methods. Sixty-six renal transplant recipients of eight Spanish centres were randomized into four branches of immunosuppressive regimen: low dose of cyclosporine, standard dose of cyclosporine, tacrolimus and sirolimus, all in addition to mycophenolate mofetil and steroids. Fifty-five patients were genotyped for SNPs in MRP2, C24T and C3972T. Pharmacokinetic sampling was done before MPA administration and up to 12 h post-dose at Day 7, 1 month and 3 months post-transplant. Relationships of area... (More)
- Background. The aim of this study was to determine the relationship between single-nucleotide polymorphisms (SNPs) in MRP2 genes and mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients of the Symphony Pharmacogenomic substudy. Methods. Sixty-six renal transplant recipients of eight Spanish centres were randomized into four branches of immunosuppressive regimen: low dose of cyclosporine, standard dose of cyclosporine, tacrolimus and sirolimus, all in addition to mycophenolate mofetil and steroids. Fifty-five patients were genotyped for SNPs in MRP2, C24T and C3972T. Pharmacokinetic sampling was done before MPA administration and up to 12 h post-dose at Day 7, 1 month and 3 months post-transplant. Relationships of area under the curve (AUC) of MPA and MPAG plasmasampling with the presence of MRP2 SNPs and with the immunosuppressive regimens were studied. Results. At steady-state conditions, MPA-reduced exposure was observed in C24T variant allele in MRP2 (CC: 68.73 +/- 6.78; *T: 48.12 +/- 4.90, P = 0.023); no significant differences linked to C3972T SNP were observed. Taking into account groups of treatment, lower MPA AUC in variant allele of C24T was only found under macrolides treatment with statistically significant differences at Month 3 (Tac and SRL, CC: 86.52 +/- 10.98 versus *T: 41.99 +/- 4.82, P = 0.001; CsA, CC: 52.31 +/- 5.30 versus *T: 54.24 +/- 8.30, P = 0.772); for C3972T, the same tendency was found but differences at steady state did not reach statistical significance. Conclusions. Renal transplant recipients T carriers of C24T MRP2 with macrolides treatment were associated with reduced MPA AUC in steady-state conditions. Patients treated (Less)
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https://lup.lub.lu.se/record/2207741
- author
- Lloberas, Nuria ; Torras, Juan ; Ma Cruzado, Josep ; Andreu, Franc ; Oppenheimer, Federico ; Sanchez-Plumed, Jaime ; Angel Gentil, Miguel ; Brunet, Merce ; Ekberg, Henrik LU and Ma Grinyo, Josep
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Immunosuppressors, MRP2, mycophenolic acid, pharmacokinetics, single-nucleotide polymorphism
- in
- Nephrology Dialysis Transplantation
- volume
- 26
- issue
- 11
- pages
- 3784 - 3793
- publisher
- Oxford University Press
- external identifiers
-
- wos:000296350400058
- scopus:80155171939
- pmid:21427078
- ISSN
- 1460-2385
- DOI
- 10.1093/ndt/gfr130
- language
- English
- LU publication?
- yes
- id
- e7081474-a630-43ed-9c26-a204634f368b (old id 2207741)
- date added to LUP
- 2016-04-01 13:23:56
- date last changed
- 2022-03-21 18:24:00
@article{e7081474-a630-43ed-9c26-a204634f368b,
abstract = {{Background. The aim of this study was to determine the relationship between single-nucleotide polymorphisms (SNPs) in MRP2 genes and mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients of the Symphony Pharmacogenomic substudy. Methods. Sixty-six renal transplant recipients of eight Spanish centres were randomized into four branches of immunosuppressive regimen: low dose of cyclosporine, standard dose of cyclosporine, tacrolimus and sirolimus, all in addition to mycophenolate mofetil and steroids. Fifty-five patients were genotyped for SNPs in MRP2, C24T and C3972T. Pharmacokinetic sampling was done before MPA administration and up to 12 h post-dose at Day 7, 1 month and 3 months post-transplant. Relationships of area under the curve (AUC) of MPA and MPAG plasmasampling with the presence of MRP2 SNPs and with the immunosuppressive regimens were studied. Results. At steady-state conditions, MPA-reduced exposure was observed in C24T variant allele in MRP2 (CC: 68.73 +/- 6.78; *T: 48.12 +/- 4.90, P = 0.023); no significant differences linked to C3972T SNP were observed. Taking into account groups of treatment, lower MPA AUC in variant allele of C24T was only found under macrolides treatment with statistically significant differences at Month 3 (Tac and SRL, CC: 86.52 +/- 10.98 versus *T: 41.99 +/- 4.82, P = 0.001; CsA, CC: 52.31 +/- 5.30 versus *T: 54.24 +/- 8.30, P = 0.772); for C3972T, the same tendency was found but differences at steady state did not reach statistical significance. Conclusions. Renal transplant recipients T carriers of C24T MRP2 with macrolides treatment were associated with reduced MPA AUC in steady-state conditions. Patients treated}},
author = {{Lloberas, Nuria and Torras, Juan and Ma Cruzado, Josep and Andreu, Franc and Oppenheimer, Federico and Sanchez-Plumed, Jaime and Angel Gentil, Miguel and Brunet, Merce and Ekberg, Henrik and Ma Grinyo, Josep}},
issn = {{1460-2385}},
keywords = {{Immunosuppressors; MRP2; mycophenolic acid; pharmacokinetics; single-nucleotide polymorphism}},
language = {{eng}},
number = {{11}},
pages = {{3784--3793}},
publisher = {{Oxford University Press}},
series = {{Nephrology Dialysis Transplantation}},
title = {{Influence of MRP2 on MPA pharmacokinetics in renal transplant recipients-results of the Pharmacogenomic Substudy within the Symphony Study}},
url = {{http://dx.doi.org/10.1093/ndt/gfr130}},
doi = {{10.1093/ndt/gfr130}},
volume = {{26}},
year = {{2011}},
}