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Selected Publication:
Shipkova, M; Armstrong, VW; Kuypers, D; Perner, F; Fabrizi, V; Holzer, H; Wieland, E; Oellerich, M; MMF Creeping Creatinine Study Group.
Effect of cyclosporine withdrawal on mycophenolic acid pharmacokinetics in kidney transplant recipients with deteriorating renal function: preliminary report.
Ther Drug Monit. 2001; 23(6):717-721
Doi: 10.1097%2F00007691-200112000-00020
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- Co-authors Med Uni Graz
- Holzer Herwig
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- Abstract:
- Mycophenolic acid (MPA) concentrations are lower in transplant recipients receiving mycophenolate mofetil (MMF) and cyclosporine compared with MMF with tacrolimus. It is not clear whether this is due to an effect of cyclosporin or tacrolimus on MPA pharmacokinetics. To study this effect, kidney transplant recipients with deteriorating renal function (n = 5) receiving cyclosporin and steroids were given mycophenolate mofetil over 4 weeks during a run-in phase (1 g/d in week 1, 1.5 g/d in week 2, 2 g/d starting from week 3). From week 5 the cyclosporin dose was reduced, and it was completely withdrawn at week 10. Creatinine, MPA, and MPA glucuronide metabolites (MPAG, AcMPAG) were determined before (week 4) and after (week 11 and week 32) cyclosporin was withdrawn. Cyclosporin withdrawal was associated with increased MPA areas under the curve (AUCs) and predose concentrations in four of the five patients. In contrast, MPAG and AcMPAG AUCs as well as predose MPAG concentrations significantly decreased. Six months after cyclosporin withdrawal, MPA AUC and predose values tended to return to initial values, whereas metabolite concentrations remained low. Cyclosporin discontinuation caused an acute increase in MPA exposure and a concomitant reduction in metabolite concentrations. The results are consistent with the hypothesis that cyclosporin attenuates the enterohepatic recirculation of MPAG/MPA.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Area Under Curve -
- Cyclosporine - adverse effects
- Drug Interactions - adverse effects
- Humans - adverse effects
- Immunosuppressive Agents - pharmacokinetics
- Kidney Transplantation - pharmacokinetics
- Male - pharmacokinetics
- Membrane Transport Proteins - pharmacokinetics
- Middle Aged - pharmacokinetics
- Multidrug Resistance-Associated Proteins - physiology
- Mycophenolic Acid - pharmacokinetics
- Find related publications in this database (Keywords)
- mycophenolic acid
- cyclosporin
- drug interaction
- mycophenolic acid pharmacokinetics
- kidney transplantation