ABSORPTION OF MYFORTIC® (ENTERIC COATED MYCOPHENOLATE SODIUM) IS PROPORTIONAL OVER A WIDE DOSE RANGE

Abstract

P771 Aims: myfortic® was developed to improve the gastrointestinal tolerability of IMPDH inhibitor therapy in kidney transplantation and has recently been approved Europe and USA. myfortic® is an advanced, enteric coated formulation of mycophenolate sodium. Unlike mycophenolate mofetil, in which the drug substance is released in the stomach, myfortic® releases mycophenolate sodium only in the high pH environment of the small intestine. The capacity of the small intestine to absorb myfortic® over a wide dose range is described below. Methods: Using a four period, randomized, cross-over design, 16 stable renal transplant patients on Neoral® received the following four oral myfortic™ doses: 180, 360, 720 and 2160 mg. Plasma mycophenolic acid (MPA) concentrations were then measured (HPLC, LOQ 0.1 ug/mL) at multiple time points and summary parameters were calculated by non-compartmental analysis. Dose-proportionality of AUC and Cmax were tested using a power model. Results: Single doses of myfortic™ were well tolerated. There were three GI tract related adverse events, abdominal pain (180 dose), constipation (720 mg dose) and diarrhea (2160 mg dose). As shown in the table below, both the maximal MPA concentration (r2=0.975) and the systemic MPA exposure (r2= 0.999) increased proportionally with dose.FigureLack-of-fit tests of both parameters were not significant. Conclusions: The small intestine is a robust absorption surface for myfortic®. Over a greater than 10-fold dose range, the maximal MPA concentration and systemic exposure delivered by myfortic® are consistent and linearly related to dose. These findings confirm the capacity of myfortic® to deliver a wide range of systemic MPA exposure which is linearly related to dose and support future clinical trials which may utilize higher or lower myfortic® dose regimens.