| Mycophenolate mofetil (MMF), a mycophenolic acid 2-ethyl ester derivant and a purified microbial products extracted from the fungus Penicillium, is commonly used after organ transplantation as an Immunosuppressive agent. It is absorbed by the body under the action of plasma esterases completely and fleetly hydrolysis into its active metabolite of MPA. MPA is a selective, efficient, reversible, non-competitive single nucleotide sub-xanthine dehydrogenase (IMPDH) inhibitor,it can Inhibit the de novo pathway of guanine nucleotide, exhaust the GMP and GTP of lymphocytes, blocke the synthesis of DNA,then Inhibit of T, B lymphocyte proliferation, and thus play its immunosuppressive effects.IMPDH has two type:typeⅠandⅡ,they are two isomers. the inhibitory effect of MPA to isomers of typeⅡis 4-5 times stronger than isomers of typeⅠ. in the resting state, the gene expression of typeⅠIMPDH isoforms in human lymphocytes is the dominant, when human lymphocytes activate, gene expression of typeⅡIMPDH was significantly increased, but the gene expression of typeⅠIMPDH isoforms basically unchanged, so typeⅡIMPDH isoforms gene expression-based in lymphocyte, therefore MPA has a strong inhibitory effect.on lymphocyte activation and proliferation. purine synthesis in T lymphocytes and B lymphocytes completely rely on denovo synthesis, purine synthesis significantly increased under mitogen stimulation through denovo synthesis, purine synthesis in other cells, is through the denovo synthesis and the salvage pathway, therefore MPA can selectively inhibit T lymphocytes and B lymphocyte activation and proliferation, while MPA's effect of inhibition of proliferation to other non-lymphocyte cells (such as endothelial cells, white blood cells, sperm cells, fibroblasts, etc.) is relatively weak effect, or even no effect.In addition, MPA can also affect the cellular immunity and humoral immunity in the body to play the role of immunosuppression:MPA also inhibited the fucose and mannose (two necessary substances in Activation of human peripheral blood lymphocytes) into glycoprotein through selective inhibition of IMPDH and depletion of intracellular GMP and GTP, reduce the expression of lymphocyte adhesion molecule through the inhibition of protein glycosylation, to achieve the role of immune suppression.Another study showed that large doses of MMF can inhibite cells proliferation of endothelial cells, fibroblasts, mesangial cells and vascular smooth muscle cell; MPA can induce apoptosis of activated T lymphocytes, inhibit NO synthesis through selectively inhibition of iNOS, then Interfere with the immune, inhibit the reactivity of T lymphocyte cells to other antigens and xenogeneic cell.People took MMF as a class of anticancer drugs to study in 60 years of the 20th century, clinical success is not achieved, later they found its immunosuppressive effects.since 90 years of the 20th century, Sollinger first reported that MMF prevent rejection successfully after renal transplantation, large-scale randomized double-blind study followed and confirmed that MMF has a positive effect to prevent and treat acute rejection in renal transplantation combined with cyclosporine (CsA) and prednisone, MMF is immediately and widely used in the prevention and treatment of rejection after organ transplantation, and is one of the most widely used immunosuppressive agents In the field of organ transplantation and autoimmune diseases.The early view that the use of MMF in renal transplantation is safety, there is no significant side effects and no need to monitor their blood concentration.as the increasingly widespread application of MMF and more and more wealth of clinical experience in the use of MMF, it is recognized that individual differences of metabolism of MMF is general, Fixed-dose drug delivery lead to differences in efficacy and bring about unnecessary toxicity. We often see in clinical still some side effects happen in patients even in the conventional dose, most drug toxicity disappear or ease by reduction of drug dose or In multiple drug; while other patients had acute rejection because of insufficient dosage of immunosuppressive drugs. Thus A single dose of drug delivery is obviously insufficient, as the growing variety of immunosuppressive agents and carrying out Individual treatment of immunosuppressive agents, people want to adjust MPA dose according to serum concentrations, to minimize the risk of transplant rejection and toxicity.In this paper, We selected 107 cases of renal transplantation patients from our transplant center in the study, monitored their mycophenolic acid plasma trough level (MPA-CO) by enzyme multiplied immunoassay technique(EMIT). Analyzed the correlation between rejection,drug toxicity and (MPA-CO) in renal transplant patients, and evaluated the role of drug concentration monitoring of MMF in renal transplantation patients.Objective to evaluate the role of drug concentration monitoring of mycophenolate mofetil (MMF) in renal transplantation patients by analysis of the correlation between rejection,drug toxicity and mycophenolic acid plasma trough level (MPA-CO)Methods We chose 107 renal transplantation patients in our center from February 2009 to April 2010,68 cases of males,39 females,18-69 years old, weighing 38-92kg, an average of 58 kg, All patients underwent preoperative hemodialysis or peritoneal dialysis, pregnancy test (-),Indicators of liver function tests were normal, hepatitis B surface antigen (-), hepatitis C antibody (-), PRA (-), We monitored their MPA-Co at five periods of month1,month2,month3 month4-6,and month7-12 After kidney transplantation and recorded drug toxicity and rejection events during each period. According to rejection and drug toxicity events occured or not the patients were divided into rejection group (groupⅠ), toxicity group (groupⅡ) and normal group (groupⅢ), Rejection group and the normal group, the toxicity group and normal group in each time period, their level of MPA-Co was to compare by two-sample test; To determine the MPA- Co cutoff value of whether patients with acute rejection or toxicity events by ROC curve. All data were analyzed using statistical software spssl3.0, p<0.05 as statistically significant.Results 72 patients were followed for 12 months, and 35 patients 6 months.13 patients experienced acute rejection, incidence of rejection was 12.1%; and a total of 38 patients with 62 clinical events of drug toxicity were seen, incidence of drug toxicity was 35.5%, in which,11 patients experienced 20 cases of Leucopenia; 14 patients experienced 23 cases of MMF-associated diarrhea; 9 patients experienced 15 cases of infection:(CMV pneumonia:5; Pneumocystis carinii pneumonia Card:1; Herpes simplex virus infection:7; Zoster virus infection:2); 4 patients experienced hepatotoxicity.There is Statistically significant differet between groupⅠand groupⅢ(month 1), groupⅡand groupⅢ, ROC curve showed an MPA level of 1.55 mg/L early post-transplantation best discriminated patients with and without rejection (sensitivity:69.2%,specificity:65.6%), and an MPA level of 2.50mg/L best discriminated patients with and without toxicity later post-transplantation (sensitivity: 67.7%,specificity:72.9%)Conclusion monitoring MPA-Co of post Renal transplant patients taking MMF is beneficial to individualize MMF dosage adjustment,and help prevent rejection and drug toxicity occur, reduce complications and improve the survival rate of graft... |
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