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Pharmacokinetics and pharmacodynamics of mycophenolate sodium (EC‐MPS) co‐administered with cyclosporine in the early‐phase post‐kidney transplantation
Author(s) -
Stracke Sylvia,
Shipkova Maria,
Mayer Jens,
Keller Frieder,
Zarghom Amir,
Yang Liying,
HenneBruns Doris,
Wieland Eberhard
Publication year - 2011
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2011.01403.x
Subject(s) - mycophenolic acid , pharmacokinetics , mycophenolate , medicine , pharmacology , imp dehydrogenase , pharmacodynamics , transplantation , renal function , immunosuppression , urology
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‐AUC 12h within the putative therapeutic range of 40–60 mg/L·h. MPA clearance was high with 29 L/h. fMPA‐AUC 12h ( r = −0.429, p = 0.04) and MPAG‐AUC 12h correlated significantly with the glomerular filtration rate, while total MPA did not. The MPAG‐AUC 12h was about 52‐fold higher than the corresponding values for MPA, whereas the AcMPAG‐AUC 12h reached about 20.4% of the respective MPA‐AUC 12h. 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.