The expression of the intercellular adhesion molecule 1 (ICAM-1) on the surface of endothelial cells plays an important role in immune-mediated processes. The induction by the proinflammatory cytokine interleukin (IL)-1beta is regulated by nuclear transcription factor kappaB (NF-kappaB). We studied the effect of an inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor, mycophenolic acid (MPA...

UNLABELLED Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported that MPA altered the tight junction (TJ)-mediated barrier function in a Caco-2 cell monolayer model system. This study investigates whether...

BACKGROUND Exposure to mycophenolic acid (MPA), the primary active metabolite of mycophenolate mofetil (MMF), is correlated with therapeutic efficacy of MMF but varies depending on the concomitantly administered immunosuppressive drugs. METHODS A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal tran...

The objective of the present study was to assess the effect of cyclosporine (CsA) on the pharmacokinetic parameters of mycophenolic acid (MPA), an active mycophenolate mofetil (MMF) metabolite, and to compare with the effect of everolimus (EVR).Anonymized medical records of 404 kidney recipients were reviewed. The main MPA pharmacokinetic parameters (AUC(0-12) and Cmax) were evaluated.The patie...

The aim of this study was to evaluate the pharmacokinetic variations of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), in both pediatric and adult patients following hematopoietic stem cell transplantation (HSCT). Twenty pediatric patients with a median age of 3 years (range 0.2-12 years) and 13 adult patients with a median age of 54 years (range 18-63 years) wer...

Cultures of the human colorectal carcinoma line, HT29, were used to assess the susceptibility to glucuronidation of the cytostatic, immunosuppressive drug mycophenolic acid (MPA) and 19 of its analogs. Removal of the metabolically vulnerable 7-hydroxyl group or its replacement by a fluorine atom, amino group, or nitrile group resulted in compounds that were completely resistant to metabolism, b...

BACKGROUND A number of studies have provided information regarding the risks and benefits of mammalian target of rapamycin inhibitors (mTOR-I) combined with calcineurin inhibitors (CNI) versus mycophenolic acid (MPA). METHODS Medline, Embase and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials comparing mTOR-I to MPA as the primary immunosuppressi...

BACKGROUND Mycophenolic acid (MPA) is an important immunosuppressive drug (ISD) prescribed to prevent graft rejection in the organ transplanted patients, however, its use is also associated with adverse side effects like sporadic gastrointestinal (GI) disturbances. Recently, we reported the MPA induced tight junctions (TJs) deregulation which involves MLCK/MLC-2 pathway. Here, we investigated t...

In humans, mycophenolic acid (MPA) is metabolized primarily by glucuronidation in the liver to mycophenolate ether glucuronide (MPAGe) and mycophenolate acyl glucuronide (MPAGa). We have previously reported that in perfused livers of TR(-) rats (lacking the Mrp2 transporter), the clearance and hepatic extraction ratio of MPA were significantly lower compared with control Wistar rats, suggesting...