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

Objective: Megestrol acetate oral suspension (MAOS) is an appetite stimulant indicated for cachexia in patients with AIDS. It is available in its original formulation, Megace(R) (MAOS), and as a nanocrystal dispersion, Megace(R) 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 (C-max) was 30% less than the fed C-max value. For MAOS, fasting C-max was 86% less than fed C-max. 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.