Journal
TRANSPLANT INTERNATIONAL
Volume 18, Issue 5, Pages 590-595Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1111/j.1432-2277.2005.00093.x
Keywords
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT); azathioprine; mizoribine; mycophenolate acid; mycophenolate mofetil; peripheral blood mononuclear cells
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Mycophenolate mofetil is currently used instead of azathioprine in clinical transplantation. However, comparative studies for the immunosuppressive potency of anti-metabolites used for organ transplantation have not been well documented. We compared the pharmacological efficacy of mycophenolic acid (MPA), 6-meraputopurine (6-MP), and mizoribine (MZ) for inhibiting purine synthesis of peripheral blood mononuclear cells (PBMCs) in vitro by a mitogen assay procedure. PBMCs were obtained from 18 renal transplant recipients before operation and 18 healthy subjects. The inhibitory efficacy of 6-MP against concanavalin A-induced PBMC blastogenesis exhibited large variations between subjects in both recipients and healthy subjects. In contrast, the pharmacological efficacy of MPA on PBMC blastogenesis showed the smallest inter-individual variation of all the purine synthesis inhibitors examined. Furthermore, the effects of MPA were almost similar in the recipients and healthy subjects. The pharmacological efficacy of MZ against PBMC blastogenesis was weaker than that of the other two agents and the inter-individual variation Of MZ IC50 against PBMCs of the patients was larger than that of MZ IC-(50) against PBMCs of healthy subjects. Reproducible immunosuppressive efficacy of MPA compared with other purinesynthesis inhibitors could be expected from the viewpoint of MPA pharmacodynamics against PBMCs in renal transplantation.
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