Absorption characteristics of EC-MPS--an enteric-coated formulation of mycophenolic sodium

Area of Science:

• Pharmacology
• Transplantation Medicine
• Gastroenterology

Background:

• Enteric-coated mycophenolate sodium is formulated to enhance mycophenolic acid (MPA) delivery.
• This advanced formulation aims to mitigate upper gastrointestinal adverse events by controlling MPA release in the small intestine.

Purpose of the Study:

• To determine the absolute bioavailability of enteric-coated mycophenolate sodium.
• To assess the dose-proportionality of enteric-coated mycophenolate sodium.
• To evaluate these parameters in stable renal transplant patients concurrently receiving cyclosporine.

Main Methods:

• Two studies were conducted involving stable renal transplant patients on cyclosporine.
• Study 1 assessed MPA absolute bioavailability by comparing oral enteric-coated mycophenolate sodium to MPA infusion.
• Study 2 evaluated the dose-proportionality of MPA and its glucuronide following administration of enteric-coated mycophenolate sodium.

Main Results:

• Mean absolute bioavailability of MPA from enteric-coated mycophenolate sodium was 0.71.
• MPA AUC(0-t) was higher following MPA infusion compared to oral enteric-coated mycophenolate sodium (42.1 vs. 28.9 microg x h/ml).
• Both MPA and MPA glucuronide exposure (AUC and Cmax) showed dose proportionality with enteric-coated mycophenolate sodium administration.

Conclusions:

• Enteric-coated mycophenolate sodium provides MPA bioavailability equivalent to mycophenolate mofetil in renal transplant patients on cyclosporine.
• The formulation exhibits dose-proportionality, ensuring predictable drug exposure.
• Enteric-coated mycophenolate sodium was well-tolerated across a dose range of 180-2,160 mg, with no serious adverse events reported.