Abstract
The pharmacokinetics of mycophenolic acid (MPA) - the active metabolite of mycophenolate mofetil (MMF) - is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA Cmax and T max were comparable in the two groups, while mean MPA AUC 0-12 was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.
| Original language | English |
|---|---|
| Pages (from-to) | 2937-2944 |
| Number of pages | 8 |
| Journal | American Journal of Transplantation |
| Volume | 5 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2005 |
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Keywords
- Cyclosporine
- Drug-drug interactions
- Kidney transplantation
- Mycophenolic acid
- Pharmacokinetics
- Sirolimus
ASJC Scopus subject areas
- Immunology
Cite this
Influence of Co-medication with sirolimus or cyclosporine on mycophenolic acid pharmacokinetics in kidney transplantation. / Cattaneo, D.; Merlini, S.; Zenoni, S.; Baldelli, S.; Gotti, E.; Remuzzi, G.; Perico, N.
In: American Journal of Transplantation, Vol. 5, No. 12, 12.2005, p. 2937-2944.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Influence of Co-medication with sirolimus or cyclosporine on mycophenolic acid pharmacokinetics in kidney transplantation
AU - Cattaneo, D.
AU - Merlini, S.
AU - Zenoni, S.
AU - Baldelli, S.
AU - Gotti, E.
AU - Remuzzi, G.
AU - Perico, N.
PY - 2005/12
Y1 - 2005/12
N2 - The pharmacokinetics of mycophenolic acid (MPA) - the active metabolite of mycophenolate mofetil (MMF) - is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA Cmax and T max were comparable in the two groups, while mean MPA AUC 0-12 was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.
AB - The pharmacokinetics of mycophenolic acid (MPA) - the active metabolite of mycophenolate mofetil (MMF) - is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA Cmax and T max were comparable in the two groups, while mean MPA AUC 0-12 was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.
KW - Cyclosporine
KW - Drug-drug interactions
KW - Kidney transplantation
KW - Mycophenolic acid
KW - Pharmacokinetics
KW - Sirolimus
UR - http://www.scopus.com/inward/record.url?scp=33644824716&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644824716&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2005.01107.x
DO - 10.1111/j.1600-6143.2005.01107.x
M3 - Article
C2 - 16303008
AN - SCOPUS:33644824716
VL - 5
SP - 2937
EP - 2944
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 12
ER -