The role of generics in transplantation: TM-MMF versus cellcept in healthy volunteers

Because several studies having revealed a relation between early graft rejection and long-term graft survival, potential benefits have been attributed to MMF. The cost of the drug is, however, prohibitive, which renders its long-term use in countries with limited income. We thus compared the pharmacokinetic profiles of a new MMF generic formulation (MM-Cept developed by Ivax CR) with those of Cellcept (Hoffman La Roche) in healthy volunteers. This open label, balanced randomized, two-treatment, two-period, two-sequence, single-dose, crossover, comparative oral bioavailability study was conducted in non-smoking adult male healthy volunteers between the ages of 18 and 45 years. The study was performed in accordance with the basic principles defined in the US 21 CFR Part 312.20 and the principles enunciated in the Declaration of Helsinki (World Medical Association Declaration of Helsinki). The subjects were given a single oral 1 g dose with a washout period of 10 days. Pharmacokinetic profiles included blood levels at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 10, 12, 16, 20, 24, 30, 36, and 48 hours following each dose. The formulations were MMCept 500 mg tablets and Cellcept 500 mg tablets. Subjects were fasted overnight and for 4 hours postdosing. Mycophenolic acid (MPA) concentrations were determined using HPLC. Physical examinations, hematology, urinalysis, and serum chemistry tests including liver enzymes were performed at screening and at the end of the study. Subjects were monitored for safety and adverse events throughout the study. Both products showed similar bioavailability. The LSM were within the limits for FDA approval (80 to 125), suggesting that the two products are equivalent and switchable.