NEWS HIGHLIGHTS
Published Studies Related to Myfortic (Mycophenolic Acid)
Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus. [2009.02]
This study was conducted to evaluate time-dependent pharmacokinetic changes and drug interactions over the first 6 months after transplantation in kidney transplant recipients receiving tacrolimus (TAC), prednisone (PRED) and mycophenolate mofetil (MMF) or sirolimus (SRL)...
Pharmacokinetic modelling of the plasma protein binding of mycophenolic acid in renal transplant recipients. [2009]
BACKGROUND AND OBJECTIVES: Renal function and the plasma albumin concentration have been shown to correlate with clearance of total mycophenolic acid (MPA). The hypothesis for the underlying mechanism is that low plasma albumin concentrations and accumulation of the glucuronide metabolite of MPA (MPAG) decrease the binding of MPA to albumin. The subsequent increase in the unbound fraction (f(u)) of MPA (MPA(u)) produces an increase in total MPA (MPA(t)) clearance. This study aimed to develop an empirical population pharmacokinetic model to describe the relationships between renal function and albumin concentration and MPAG, MPA(u) and MPA(t), in order to provide insight into the mechanism by which renal function and plasma albumin affect the disposition of MPA... CONCLUSION: The model shows that low CL(CR), low plasma albumin concentrations and high MPAG concentrations decrease MPA(t) exposure by affecting MPA binding to albumin.
AcylMPAG Plasma Concentrations and Mycophenolic Acid-Related Side Effects in Patients Undergoing Renal Transplantation Are Not Related to the UGT2B7-840G>A Gene Polymorphism. [2008.08]
Mycophenolic acid (MPA) is metabolized primarily by glucuronidation to form the biologically inactive 7-O-glucuronide conjugate (MPAG), which is the major urinary excretion product. MPA is also converted to acyl-glucuronide metabolite (AcylMPAG), which has been suggested to be involved in the generation of MPA-related adverse events such as diarrhea or leucopenia.
Plasma concentrations of mycophenolic acid acyl glucuronide are not associated with diarrhea in renal transplant recipients. [2007.07]
The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL)...
Reduced-exposure cyclosporine is safe and efficacious in de novo renal transplant recipients treated with enteric-coated mycophenolic acid and basiliximab. [2007.03]
BACKGROUND: The lower limit of exposure to calcineurin inhibitors has not yet been established in de novo renal transplant patients receiving mycophenolic acid therapy with basiliximab... CONCLUSIONS: These results indicate that enteric-coated mycophenolate sodium with reduced-exposure cyclosporine, steroids and basiliximab induction has an excellent therapeutic effect and is safe in de novo kidney transplant recipients. Lower C2 targets than previously recommended, particularly early post-transplant, do not appear to be associated with compromised efficacy.
Clinical Trials Related to Myfortic (Mycophenolic Acid)
Patient Reported Outcomes in Renal Transplant Patients Tolerating Gastrointestinal (GI) Symptoms Converted to Myfortic (EC-MPS) [Active, not recruiting]
Hypothesis: Presently, some patients' mycophenolate mofetil (MMF.,Cellcept) related
gastrointestinal (GI) symptoms are not being spontaneously reported. It is postulated that a
conversion to enteric-coated mycophenolate sodium (EC-MPS.,Myfortic) from MMF will reduce the
objectively measured GI symptom burden and improve GI-related quality of life.
Primary Objective: To determine the incidence of GI-related symptoms and the health related
quality of life of renal transplant patients that are currently tolerating MMF. Assessed by
GSRS and GIQLI.
Secondary Objective: To determine the impact on GI symptoms and the health related quality of
life of renal transplant patients converted from MMF to Myfortic. Assessed by GSRS and
GIQLI.
Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol [Active, not recruiting]
Mycophenolate sodium (Myfortic®) is an antiproliferative immunosuppressant used in
transplantation. It was developed with the intention of improving the gastrointestinal side
effect profile of mycophenolate mofetil (CellCept®). Mycophenolate sodium is formulated as an
enteric coated tablet that releases mycophenolic acid (MPA) which in turn inhibits inosine
monophosphate dehydrogenase (IMPDH).1 Through inhibition of IMPDH the de novo pathway of
purine synthesis, which T and B lymphocytes rely on for proliferation, is blocked. 1 The
pharmacokinetic profile of mycophenolate sodium has mainly been studied in combination with
cyclosporine and steroids. 2 There is little information on the pharmacokinetics of
mycophenolate sodium in combination with tacrolimus3 and currently no published information
in steroid withdrawal. The metabolism and pharmacokinetics of mycophenolic acid differ when
combined with cyclosporine or tacrolimus, leading to increased area under the curve (AUC) and
Cmin with tacrolimus. 4 The decrease in AUC with cyclosporine is due to an inhibition of MPAG
excretion5, thus preventing the enterohepatic recirculation of MPAG and conversion back to
MPA that is seen with tacrolimus. Mycophenolate sodium pharmacokinetics in the fed state have
demonstrated a decrease of 33% in Cmax compared to a fasting state, as well as a delay in
Tmax and lag time. 1 However AUC, representing systemic exposure to MPA, was not significantly
effected by food. 1 The AUC values may vary by 20% or greater when mycophenolate sodium is
administered with food. All current published data on the pharmacokinetics of MPA have been
in patients receiving chronic corticosteroids as part of their immunosuppression regimen. As
immunosuppression minimization, and especially corticosteroid withdrawal, become more popular
it is important to understand how mycophenolate sodium and its metabolites behave in a 2 drug
maintenance immunosuppression regimen. We propose to study the pharmacokinetic profile of
mycophenolate sodium in patients on tacrolimus dose adjusted based on levels, and a steroid
withdrawal protocol.
Campath, Rituximab, and Myfortic With Short-Course Calcineurin Inhibitor Therapy in Renal Transplanation [Active, not recruiting]
The hypothesis of this study is that lymphocyte depletion by Campath-1H and rituximab will
obviate the need for long-term calcineurin inhibitors in renal transplantation. Most
successful strategies to date have relied on the use of either tacrolimus or cyclosporine for
an indefinite period of time. However, the advantage of a long term, calcineurin inhibitor
free regimen may include improved renal allograft function, a lower incidence of
hypertension, diabetes, and less drug related side effects. This is a non-randomized
open-label pilot trial in 30 adult renal transplant patients. Subjects will receive 2 doses
of Campath-1H (30mg given on Day 0 and Day 1) and a single dose of Rituximab (375mg/m2) on
Day 0, given intra-operative. Subjects will take maintenance doses of prednisone and enteric
coated mycophenolate sodium (Myfortic™). Subject will also be given cyclosporine (Neoral®)
therapy for approximately 2 weeks (10-20 days).
Study of Myfortic in Combination With Tacrolimus and Thymoglobulin in Early Corticosteroid Withdrawal [Active, not recruiting]
To determine the safety and efficacy of a new formulation of Myfortic in combination with
tacrolimus and thymoglobulin.
Study of Gastrointestinal Side Effects in African American Kidney Transplant Recipients Treated With CellCept or Myfortic [Recruiting]
Myfortic (enteric-coated mycophenolate sodium) has been shown to have similar effectiveness
to CellCept (mycophenolate mofetil) in preventing rejection in kidney transplant recipients.
However, Myfortic has been thought to possibly be associated with fewer gastrointestinal
side effects. CellCept and Myfortic pharmacokinetics (how the drug is absorbed and broken
down) have not been well-studied in African American kidney transplant recipients. The
investigators are interested in studying Myfortic and CellCept pharmacokinetics and
gastrointestinal side effects in African American kidney transplant recipients.
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