Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 9/23/2012 |
| Start Date: | December 2007 |
| End Date: | July 2011 |
| Contact: | Lonnie Smith, PharmD |
| Email: | lonnie.smith@hsc.utah.edu |
| Phone: | 801-585-6282 |
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
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.
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
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