Pharmacokinetics
The oral bioavailability of MGA is approximately 100%. After a single low oral dose of 4 mg MGA, peak serum concentrations of MGA were about 7 ng/dL (18 nmol/L) and occurred after 3 hours. Following a single high oral dose of 160 mg micronized MGA in men, peak circulating levels of MGA were 125 ng/mL (325 nmol/L) and occurred after 6.3 hours. This study found that micronized MGA at this dose showed considerably improved absorption relative to its conventional tablet form. In terms of plasma protein binding, MGA is bound mostly to albumin (82.4%) and is not bound to sex hormone-binding globulin or to corticosteroid-binding globulin. MGA metabolized in the liver mainly by hydroxylation of the C21, C2α, and C6 positions, as well as by reduction and conjugation. Its elimination half-life is 34 hours on average, with a range of 13 to 105 hours. MGA is excreted 57 to 78% in urine and 8 to 30% in feces.At high doses, MGA appears to have far greater bioavailability and potency than medroxyprogesterone acetate, regardless of whether the route of administration of the latter is oral or parenteral. Following oral administration of 80 to 160 mg MGA or 500 to 1,000 mg medroxyprogesterone acetate, circulating levels of MGA were 2- to 10-fold higher than those of medroxyprogesterone acetate. Similar findings have been found for oral MGA relative to medroxyprogesterone acetate administered via intramuscular injection. MGA also reaches steady-state levels more quickly than medroxyprogesterone acetate.
Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia. It is also used to treat breast cancer and endometrial cancer, and has been used in birth control. MGA is generally formulated alone, although it has been combined with estrogens in birth control formulations. It is usually taken by mouth.Side effects of MGA include increased appetite, weight gain, vaginal bleeding, nausea, edema, low sex hormone levels, sexual dysfunction, osteoporosis, cardiovascular complications, glucocorticoid effects, and others. MGA is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak partial androgenic activity, weak glucocorticoid activity, and no other important hormonal activity. Due to its progestogenic activity, MGA has antigonadotropic effects. The mechanism of action of the appetite stimulant effects of MGA is unknown.MGA was discovered in 1959 and was introduced for medical use, specifically in birth control pills, in 1963. It may be considered a "first-generation" progestin. The medication was withdrawn in some countries in 1970 due to concerns about mammary toxicity observed in dogs, but this turned out not to apply to humans. MGA was approved for the treatment of endometrial cancer in 1971 and wasting syndromes in 1993. It is marketed widely throughout the world.