Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics

Area of Science:

• Pharmacology
• Transplantation Medicine
• Clinical Pharmacy

Background:

• Mycophenolate mofetil (MMF) is a key immunosuppressant in organ transplantation.
• An intravenous (i.v.) formulation of MMF is available for patients intolerant to oral intake.
• Renal transplant recipients often require flexible drug administration routes.

Purpose of the Study:

• To evaluate the pharmacokinetics (PK) and safety of i.v. MMF compared to oral MMF in renal transplant recipients.
• To determine if i.v. MMF provides equivalent exposure to oral MMF.
• To assess the safety profile of i.v. MMF in the immediate post-transplant period.

Main Methods:

• Two studies were conducted: an open-label PK study (n=45) and a double-blind safety study (n=153).
• Participants received i.v. MMF 1 g every 12 hours (Q12h) or placebo.
• Blood samples were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations using high-performance liquid chromatography.

Main Results:

• The area under the concentration curve (AUC) for MPA was significantly higher with i.v. MMF compared to oral MMF (40.8 vs. 32.9 microg x h/mL, p < 0.001).
• Overall adverse events were similar between i.v. MMF and placebo groups.
• Injection site phlebitis and thrombosis were noted in 4% of patients receiving i.v. MMF.

Conclusions:

• Intravenous MMF 1 g twice daily provides at least equivalent efficacy to oral MMF.
• The i.v. formulation offers an acceptable alternative for renal transplant patients unable to tolerate oral medication.
• The safety profile of i.v. MMF is comparable to oral MMF, with specific local site reactions observed.