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

Deschamps B, Musaji N, Gillespie JA - Int J Nanomedicine (2009)

Bottom Line: 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.Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects.

View Article: PubMed Central - PubMed

Affiliation: SFBC Anapharm, Montreal, Canada.

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2747353&req=5

f2-ijn-4-185: 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.

Mentions: The PK parameters for MA-ES 625 mg/5 mL administered under fed and fasting conditions are shown in Table 1. AUC0–∞ decreased from 16,268 ng·h/mL in the fed state to 12,095 ng·h/mL in the fasting state. The mean Cmax decreased from 1,618 ng/mL in the fed to 1,133 ng/mL in the fasting state. Absorption of MA-ES based on AUC and Cmax showed a decrease of 26% and 30%, respectively, in the fasting compared with the fed state. The fed to fasting ratios (90% CI) of least-squares means for AUC0–t, AUC0–∞, and Cmax, were 1.36 (1.26 to 1.47), 1.36 (1.26 to 1.47), and 1.48 (1.28 to 1.71), respectively, indicating that consumption of a high-fat meal increased the rate and extent of absorption of MA-ES. Figure 2 shows the profile for mean plasma concentration over time for MA-ES administered under fed or fasting conditions.


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

Deschamps B, Musaji N, Gillespie JA - Int J Nanomedicine (2009)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747353&req=5

f2-ijn-4-185: 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.
Mentions: The PK parameters for MA-ES 625 mg/5 mL administered under fed and fasting conditions are shown in Table 1. AUC0–∞ decreased from 16,268 ng·h/mL in the fed state to 12,095 ng·h/mL in the fasting state. The mean Cmax decreased from 1,618 ng/mL in the fed to 1,133 ng/mL in the fasting state. Absorption of MA-ES based on AUC and Cmax showed a decrease of 26% and 30%, respectively, in the fasting compared with the fed state. The fed to fasting ratios (90% CI) of least-squares means for AUC0–t, AUC0–∞, and Cmax, were 1.36 (1.26 to 1.47), 1.36 (1.26 to 1.47), and 1.48 (1.28 to 1.71), respectively, indicating that consumption of a high-fat meal increased the rate and extent of absorption of MA-ES. Figure 2 shows the profile for mean plasma concentration over time for MA-ES administered under fed or fasting conditions.

Bottom Line: 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.Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects.

View Article: PubMed Central - PubMed

Affiliation: SFBC Anapharm, Montreal, Canada.

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.

Show MeSH
Related in: MedlinePlus