Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil

Area of Science:

• Pharmacology
• Transplantation Medicine
• Gastroenterology

Background:

• Mycophenolate mofetil (MMF) is a standard immunosuppressant for renal transplant recipients.
• MMF therapy is linked to significant gastrointestinal adverse effects.
• Enteric-coated mycophenolate sodium (EC-MPS) is designed for targeted MPA delivery in the small intestine.

Purpose of the Study:

• To compare the relative bioavailability of two EC-MPS doses (640 mg and 720 mg) against MMF (1000 mg).
• To evaluate MPA and MPA glucuronide exposure and pharmacokinetic profiles.
• To assess the tolerability of EC-MPS compared to MMF.

Main Methods:

• A single-center, open-label, randomized, three-way crossover study.
• Involved 24 stable Caucasian renal transplant patients on cyclosporine-based immunosuppression.
• Compared EC-MPS (640 mg and 720 mg) with MMF (1000 mg) for MPA and MPA glucuronide bioavailability.

Main Results:

• Both EC-MPS doses demonstrated bioequivalent mean MPA exposure (AUC(0-infinity)) to MMF.
• Median Tmax was significantly delayed for EC-MPS (2.0 h) versus MMF (0.75 h), confirming enteric coating.
• EC-MPS doses were bioequivalent to MMF for MPA glucuronide AUC and Cmax.
• All treatments were well tolerated.

Conclusions:

• Enteric-coated mycophenolate sodium (EC-MPS) provides comparable mycophenolic acid (MPA) exposure to mycophenolate mofetil (MMF).
• The delayed Tmax suggests effective enteric delivery of EC-MPS.
• The 720 mg EC-MPS dose was selected for further Phase III studies due to its close approximation of MMF MPA exposure.