Background. This study investigated the effect of St John’s wort (SJW) extract on the pharmacokinetics of the immunosuppressants tacrolimus (TAC) and mycophenolic acid (MPA). Methods. Ten stable renal transplant patients received 600 mg SJW extract for 14 days in addition to their regular regimen of TAC and mycophenolate mofetil. Results. Dose-corrected AUC(0–12) of TAC decreased significantly ...

Exposure to toxaphene, an environmentally persistent mixture of chlorinated terpenes previously utilized as an insecticide, has been associated with various cancers and diseases such as amyotrophic lateral sclerosis. Nevertheless, the cellular and molecular mechanisms responsible for these toxic effects have not been established. In this study, we used a functional approach in the model eukaryo...

Mycophenolic acid (MPA) is the metabolized product and active element of mycophenolate mofetil (MMF) that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH) that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, ...

Mycophenolic acid (MPA) has become the cornerstone in the treatment of lupus nephritis. However, response rates are still far from ideal in clinical trials. Uncertainty exists regarding the correct dosing of MPA, and the recommended doses vary between recently published guidelines. Side effects are an additional problem resulting in frequent dose reduction and possible suboptimal exposure.In th...

BACKGROUND AND OBJECTIVES Mycophenolate mofetil (MMF) is an immunosuppressive drug used in renal transplant patients. Upon oral administration it is hydrolyzed to the active agent mycophenolic acid (MPA). In renal transplant recipients, MMF therapy is optimal when the area under the curve of MPA is 30 to 60 mg·h/L. When MMF doses are adjusted, a linear relationship between dose and MPA exposure...

Mycophenolic acid (MPA) is part of the immunosuppressant therapy for transplant recipients. This study examines the role of the canalicular transporter, Mrp2, and the effect of cyclosporin A (CsA), on the biliary secretion of the ether (MPAGe) and acyl (MPAGa) glucuronides of MPA. Isolated livers from Wistar rats (n = 6), or Wistar TR- rats (n = 6) were perfused with MPA (5 mg/l). A third group...

As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Her...

Mycophenolate mofetil, the prodrug form of the immunosuppressive agent mycophenolic acid (MPA), is currently in clinical trials evaluating its effectiveness in transplant recipients. In this study, we validated an ultrafiltration system for the reliable measurement of free MPA. Using this technique, we evaluated factors that might be important in modulating the free fraction of this drug. Human...

This study aimed to investigate the association between longitudinal exposure to mycophenolic acid (MPA) and acute rejection (AR) risk in the first year after renal transplantation, and to propose MPA exposure targets conditionally to this association. A joint model, adjusted for monitoring strategy (fixed-dose versus concentration-controlled) and recipient age, was developed; it combined a mix...

OBJECTIVE Mycophenolic acid (MPA) exposure is associated with clinical outcomes in hematopoietic cell transplant (HCT) recipients. Various drug interaction studies, predominantly in healthy volunteers or solid organ transplant recipients, have identified medications which impact MPA pharmacokinetics. Recipients of nonmyeloablative HCT, however, have an increased burden of comorbidities, potenti...