Food effect on the bioavailability of two distinct formulations of megestrol acetate oral suspension

Abstract

Benoit Deschamps1, Naomi Musaji2, John A Gillespie21SFBC Anapharm, Montreal, Canada; 2Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc., Woodcliff Lake, NJ, USAObjective: Megestrol acetate oral suspension (MAOS) is an appetite stimulant indicated for cachexia in patients with AIDS. It is available in its original formulation, Megace® (MAOS), and as a nanocrystal dispersion, Megace® ES (MA-ES). Three studies were conducted to evaluate the pharmacokinetic properties of these formulations under fed and fasting conditions.Methods: An open-label, crossover trial was conducted in 24 healthy males randomized to MA-ES 625 mg/5 mL given with a high-calorie, high-fat meal, or after an overnight fast. Blood samples were drawn at multiple time points and pharmacokinetic parameters were determined. Two separate, open-label reference studies evaluated MAOS 800 mg/20 mL in 40 fed or 40 fasting healthy male volunteers.Results: In fasting MA-ES subjects, the average maximum concentration (Cmax) was 30% less than the fed Cmax value. For MAOS, fasting Cmax was 86% less than fed Cmax. In fasting subjects, the area under the curve was 12,095 ng⋅h/mL for MA-ES, and 8,942 ng⋅h/mL for MAOS. In fed subjects, the absorption of the two formulations was comparable.Conclusion: Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects. MA-ES may be a preferred formulation of megestrol acetate when managing cachectic patients whose caloric intake is reduced.Keywords: megestrol acetate, bioavailability, cachexia, nanocrystal technology, appetite stimulant