Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol

Kidney Transplant Clinical Trial

Official title: Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol in Combination With Tacrolimus in Stable Renal Transplant Recipients in the Fed and Fasting State

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

n/a

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant

• NCT number: NCT00585468
• Study type: Interventional
• Source: University of Utah
• Status: Completed
• Phase: Phase 4
• Start date: December 2007
• Completion date: July 2011