Pharmacodynamic monitoring of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable kidney-allograft recipients.
BACKGROUND
The formulations of mycophenolic acid, i.e., mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), seem to have different pharmacokinetic profiles. The aim of this study was to compare the effects MMF and EC-MPS on T-cell proliferation, T-cell activation, T-cell function, and lymphocyte subsets. CLINICAL STUDY AND METHODS: Ten stable kidney-transplant patients on standard maintenance therapy of tacrolimus and MMF (1 g/d), with or without steroids, were converted from MMF to EC-MPS at equivalent dose (720 mg/d). Tacrolimus and steroid doses remained unchanged before, and at 1, 2, 3, and 6 months (M) after conversion. Intra T-lymphocyte cytokines IL-2 and TNF-alpha, lymphocyte-activation surface markers (CD25 and CD71), T-cell proliferation (PCNA+ PI(high)), total lymphocyte count, as well as lymphocytes subsets (CD2, CD3, CD4, CD8, CD19, NK cells) were measured by flow cytometry before conversion and at M1, M2, M3, and M6.


RESULTS
We found no significant differences of MMF versus EC-MPS on lymphocyte function. T-cell proliferation and T-cell activation (CD25 and CD71 expression), but not cytokine expression (TNF-alpha and IL-2), showed a trend to increase after conversion from MMF to EC-MPS. Total lymphocyte, CD2, CD3, CD4, CD8, and NK cells counts were not significantly modified.


CONCLUSIONS
This study revealed a trend to a lower immunosuppression with EC-MPS as compared to MMF in stable renal transplant patients.
Böhler
Torsten
T
INSERM U858, Equipe 10, IFR 31, Institut Louis Bugnard, Bâtiment L3, CHU Rangueil, France. boehlert@toulouse.inserm.fr
Canivet
Cindy
C
Galvani
Sylvain
S
Therville
Nicole
N
Salvayre
Robert
R
Negre-Salvayre
Anne
A
Durand
Dominique
D
Thomsen
Mogens
M
Rostaing
Lionel
L
Kamar
Nassim
N
D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016207:Cytokines / Q000096:biosynthesis; D016903:Drug Monitoring; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology
D016207:Cytokines; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid; D016559:Tacrolimus