Adrenal steroids as parameters of the bioavailability of MA and MPA.

Serum levels of cortisol (C), androstenedione (A), dehydroepiandrosterone (D), estrone (E1) and estradiol (E2) were chosen as parameters to compare the bioavailability of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in postmenopausal patients with advanced breast cancer. In 36 patients randomized to MPA, the levels of A (13% vs. 19%) and C (6% vs. 8%) were slightly lower than in 36 patients on MA, but D-levels (68% vs. 59%) and E1 or E2, were similar. The correlation between baseline C and A disappeared during treatment. Treatment levels of E1 and E2 were correlated. There was no correlation between individual drug levels and any steroid, indicating a maximal suppression. After ingestion of a single dose of MA or MPA, peak levels were found after 2-3 h for MA and 3-4 h for MPA. Four hours after ingestion, the levels of A and C were similar, 40-60% of baseline values, while D levels remained unaltered. Doubling the dose of either drug did not enhance hormone suppression, indicating that the drug dosage is maximally suppressive. In conclusion, although the median serum MA levels are double those of MPA, suppression of A, C and D is usually similar, with corresponding estrogen levels, demonstrating a comparable and maximal bioavailability. Higher dosages of MA or MPA will not increase their pharmacological effects any further.