Conflict of interest: The study was partly funded by Novartis.
Pharmacokinetics and pharmacodynamics of mycophenolate sodium (EC-MPS) co-administered with cyclosporine in the early-phase post-kidney transplantation
Article first published online: 7 FEB 2011
© 2011 John Wiley & Sons A/S
Volume 26, Issue 1, pages 57–66, January/February 2012
How to Cite
Stracke, S., Shipkova, M., Mayer, J., Keller, F., Zarghom, A., Yang, L., Henne-Bruns, D. and Wieland, E. (2012), Pharmacokinetics and pharmacodynamics of mycophenolate sodium (EC-MPS) co-administered with cyclosporine in the early-phase post-kidney transplantation. Clinical Transplantation, 26: 57–66. doi: 10.1111/j.1399-0012.2011.01403.x
- Issue published online: 7 FEB 2012
- Article first published online: 7 FEB 2011
- Accepted for publication 29 November 2010
- acyl glucuronide;
- enteric-coated mycophenolate sodium;
- kidney transplantation;
- mycophenolic acid
Stracke S, Shipkova M, Mayer J, Keller F, Zarghom A, Yang L, Henne-Bruns D, Wieland E. Pharmacokinetics and pharmacodynamics of mycophenolate sodium (EC-MPS) co-administered with cyclosporine in the early-phase post-kidney transplantation. Clin Transplant 2012: 26: 57–66. © 2011 John Wiley & Sons A/S.
Abstract: Mycophenolate drug levels are decreased by co-administration of cyclosporine. However, mycophenolate levels may be associated with insufficient immunosuppression.
We investigated the pharmacokinetics of 720 mg mycophenolate sodium (EC-MPS) and inosine monophosphate dehydrogenase (IMPDH) activity under co-medication with cyclosporine and steroids within the first 30 d after kidney transplantation (n = 24). Blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h after the morning dose. Plasma concentrations of mycophenolic acid, its glucuronide metabolites (MPAG; AcMPAG), and free MPA were determined using validated HPLC-DAD. IMPDH activity in leukocytes was analyzed chromatographically.
Only six of 24 patients had an MPA-AUC12h within the putative therapeutic range of 40–60 mg/L·h. MPA clearance was high with 29 L/h. fMPA-AUC12h (r = −0.429, p = 0.04) and MPAG-AUC12h correlated significantly with the glomerular filtration rate, while total MPA did not. The MPAG-AUC12h was about 52-fold higher than the corresponding values for MPA, whereas the AcMPAG-AUC12h reached about 20.4% of the respective MPA-AUC12h. We found significant correlations between IMPDH inhibition and MPA concentration (r = −0.665; p < 0.0001), fMPA (r = −0.446; p = 0.003), and AcMPAG (r = −0.459; p = 0.002) but not with MPAG.
Only 25% of the patients attained the therapeutic range for MPA-AUC under standard EC-MPS dose during the early-phase post-transplantation. We recommend that EC-MPS should be given in higher doses (3 × 720 mg) in the early post-transplant period when co-administered with cyclosporine.