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

Abstract

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 (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 (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.

Keywords: appetite stimulant; bioavailability; cachexia; megestrol acetate; nanocrystal technology.

Figures

Figure 1

Flow diagrams for pharmacokinetic studies of a nanocrystal dispersion of megestrol acetate (MA-ES) 625 mg/5 mL and a micronized formulation of megestrol acetate oral suspension (MAOS) 800 mg/20 mL in fed and fasting subjects. Note: a800 to 1000 calories, ∼50% fat.

Figure 2

Mean plasma concentration profilea for a nanocrystal dispersion of megestrol acetate (MA-ES) 625 mg/5 mL in fed and fasting states (N = 23). Data from Study 1. Note: aMean plasma concentration across all subjects at each time point.

Figure 3

Mean plasma concentration profilea for a micronized formulation of megestrol acetate oral suspension (MAOS) 800 mg/20 mL in fed and fasting states. Data from Study 2, MAOS in fed (N = 32) subjects, and Study 3, MAOS in fasting (N = 36) subjects. Note: aMean plasma concentration across all subjects at each time point.

Figure 4

Food effect differences between a nanocrystal dispersion of megestrol acetate (MA-ES) 625 mg/5 mL and a micronized formulation of megestrol acetate oral suspension (MAOS) 800 mg/20 mL. a800 to 1000 calories, ∼50% fat. bData in fed subjects from Study 1, MA-ES (N = 23), and Study 2, MAOS (N = 32). cData in fasting subjects from Study 1, MA-ES (N = 23), and Study 3, MAOS (N = 36).