PHARMACOKINETICS OF ERL080A: A NEW ENTERIC COATED FORMULATION OF MYCOPHENOLIC ACID-SODIUM

Abstract

787 ERL080A is a new formulation of mycophenolic acid-sodium which is being developed for use as an immunosuppressive agent in kidney transplantation. ERL080A was designed to efficiently deliver systemic mycophenolic acid (MPA) exposure in an enteric coated formulation with potentially improved gastrointestinal tolerability. An initial human relative bioavailability study of ERL080A compared to CellCept® (MMF) allowed the selection of an ERL080A tablet strength of 360 mg for further development. This ERL080A strength was chosen to yield a systemic MPA exposure bioequivalent to that of 500 mg MMF. The following bioequivalence trial was conducted. In a single center, open-label, randomized, cross-over design 24 stable renal transplant patients received a single oral dose of either ERL080A 720 mg or MMF 1000 mg. Plasma MPA and mycophenolic acid glucuronide (MPAG) concentrations were measured by HPLC for 48 hours post dose. There were no serious adverse events and there were nine mild, reversible adverse events distributed throughout the treatment groups. The pharmacokinetic properties of the two treatments are compared in Table 1 [Tmax (median, hr), Cmax (mean, μg/mL) and AUC0-t (mean, μgxhr/mL)].Table 1The ratio of ERL080A and MMF MPA AUC geometric means was 1.0. Conclusions: Both study drugs in single doses were well tolerated in this population of stable renal transplant patients. A dose of ERL080A 720 mg resulted in bioequivalent exposure (AUC) of both, MPA (90% CI:0.91-1.10) and the solitary, inactive metabolite, MPAG (90% CI: 0.86-0.98) when compared to MMF 1000 mg. The enteric coated design of ERL080A appears to be functioning, given the prolonged Tmax of plasma MPA compared to MMF. Future clinical trials will utilize the enteric coated 360 mg ERL080A tablet.