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

This study has been completed.
Information provided by (Responsible Party):
University of Utah Identifier:
First received: December 21, 2007
Last updated: October 18, 2012
Last verified: October 2012
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.

Condition Intervention Phase
Kidney Transplant
Drug: Myfortic
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Outcomes measured will include Cmax, Cmin, Tmax and AUC for Myfortic metabolites (MPA, MPAG, AcMPAG, freeMPA) and tacrolimus [ Time Frame: Dec 2007-Dec 2008 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Outcomes measured will include Cmax, Cmin, Tmax and AUC for Myfortic metabolites (MPA, MPAG, AcMPAG, freeMPA) and tacrolimus [ Time Frame: Dec 2007-Dec 2008 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: December 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Drug: Myfortic
Other Names:
  • mycophenolate sodium
  • mycophenolic acid


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Renal transplant recipients greater than 18 years of age, who have given written consent

Exclusion Criteria:

  • taking medications that will interfere with the metabolism of the metabolism of tacrolimus or mycophenolate sodium
  • experienced an acute rejection episode prior to their pharmacokinetic profiles and if they have a serum creatinine >2 mg/dL
  • neutropenia (ANC < 1.3x103/mL)
  • received a previous transplant other than a kidney
  • receiving chronic steroids at time of transplant
  • known hypersensitivity to tacrolimus, mycophenolate mofetil, mycophenolate sodium, mycophenolic acid or any of its excipients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00585468

Sponsors and Collaborators
University of Utah
Principal Investigator: Fuad Shihab, MD University of Utah
  More Information

Responsible Party: University of Utah Identifier: NCT00585468     History of Changes
Other Study ID Numbers: 15121  Award# CERL080AUS33 
Study First Received: December 21, 2007
Last Updated: October 18, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on April 27, 2016