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).

Mean plasma concentrations of megestrol acetate after oral administration of 625 mg of Megace® ES (megestrol acetate) oral suspension and 800 mg of megestrol acetate oral suspension to healthy volunteers under fed conditions

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 150mg and 675mg 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 625mg 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 800mg in the original formulation. There was no difference in safety following administration in the fed state, therefore Megace® ES could be taken without regard to meals.

Table 1 - Pharmacokinetic Studies Conducted with Megace® ES

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