DESCRIPTION
DESCRIPTION
Megace ® ES (megestrol acetate) oral suspension contains megestrol acetate, a synthetic derivative of the naturally occurring steroid hormone, progesterone. Megestrol acetate is a white, crystalline solid chemically designated as 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate. Solubility at 37° C in water is 2 mcg per mL, solubility in plasma is 24 mcg per mL. Its molecular weight is 384.52.
The chemical formula is C24H32O4 and the structural formula is represented as follows:   
Megace ® ES (megestrol acetate) is a concentrated formula supplied as an oral suspension containing 125 mg of megestrol acetate per mL.
Megace ® ES (megestrol acetate) oral suspension contains the following inactive ingredients: alcohol (max 0.06% v/v from flavor), artificial lime flavor, citric acid monohydrate, docusate sodium, hydroxypropyl methylcellulose (hypromellose), natural and artificial lemon flavor, purified water, sodium benzoate, sodium citrate dihydrate, and sucrose.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY
There are several analytical methods used to estimate megestrol acetate plasma concentrations, including gas chromatography-mass fragmentography (GC-MF), high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). The GC-MF and HPLC methods are specific for megestrol acetate and yield equivalent concentrations. The RIA method reacts to megestrol acetate metabolites and is, therefore, non-specific and indicates higher concentrations than the GC-MF and HPLC methods. Plasma concentrations are dependent, not only on the method used, but also on intestinal and hepatic inactivation of the drug, which may be affected by factors such as intestinal tract motility, intestinal bacteria, antibiotics administered, body weight, diet and liver function.
Mechanism of Action
Several investigators have reported on the appetite enhancing property of megestrol acetate and its possible use in cachexia. The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time.
Pharmacokinetic Properties:
Plasma concentrations of megestrol acetate after administration of 625 mg (125 mg/mL) of Megace® ES oral suspension are equivalent under fed conditions to 800 mg (40 mg/mL) of megestrol acetate oral suspension (see figure below).                                  
In order to characterize the dose proportionality of Megace® ES, pharmacokinetic studies across a range of doses were conducted when administered under fasting and fed conditions. Pharmacokinetics of megestrol was linear in the dosing range between 150 mg and 675 mg after Megace® ES administration regardless of meal condition. The Cmax and AUC under a high fat meal were increased by 48% and 36%, respectively, compared to those under the fasting after 625 mg Megace® ES administration (Table 1). However, a high fat meal significantly increased AUC and Cmax of megestrol to 2-fold and 7-fold, respectively, compared to those under fasting condition after administration of 800 mg in the original formulation. There was no difference in safety following administration in the fed state, therefore Megace® ES cou