Plasma concentrations of megestrol acetate and medroxyprogesterone acetate after single oral administration to healthy subjects.

Plasma concentrations of megestrol acetate (MA) were measured by radioimmunoassay (RIA) after a single oral dose of 60 mg either in the form of one tablet, or four 15 mg tablets, to 10 women 21-40 years old using a cross-over design. No statistically significant difference between the two preparations was observed with respect to plasma concentrations, the area under the curve from 0 to 24 h or the maximum concentration (c(max)). For comparison, data are presented on the plasma level of medroxyprogesterone acetate (MPA) following a single oral dose of 100 mg given using a cross-over design in two different tablet forms to 10 healthy men, when no significant difference was observed for these parameters. The mean c(max) for MA after 2.6 h was 43.9 ng/ml (range 21.7-87.7 ng/ml), whereas that for MPA at 3.1 h was 13.1 ng/ml (range 4.4-29.5 ng/ml) despite the higher dose. After 24 h immunoreactive MA and MPA ranged from 9.6 to 29.0 ng/ml and from 0.2 to 4.0 ng/ml respectively. Moreover, it was found that petroleum ether extraction gives the most specific result by RIA, although considerable amounts of metabolites are still co-estimated. By comparison with selected ion monitoring using GC-MS, metabolite interference in RIA increases with time after administration of the steroids and is considerably greater for MPA than for MA. It is concluded that after oral administration the relative bioavailability of MA is significantly better than that of MPA.