It has about 100 to 500% of the affinity of aldosterone for the MR and about 50 to 230% of the affinity of progesterone for the MR. Drospirenone is about 5.5 to 11 times more potent as an antimineralocorticoid than spironolactone in animals. Accordingly, 3 to 4 mg drospirenone is said to be equivalent to about 20 to 25 mg spironolactone in terms of antimineralocorticoid activity. It has been said that the pharmacological profile of drospirenone more closely resembles that of progesterone than other progestins due to its antimineralocorticoid activity. Drospirenone is the only clinically used progestogen with prominent antimineralocorticoid activity besides progesterone. For comparison to progesterone, a 200 mg dose of oral progesterone is considered to be approximately equivalent in antimineralocorticoid effect to a 25 to 50 mg dose of spironolactone. Both drospirenone and progesterone are actually weak partial agonists of the MR in the absence of mineralocorticoids.Due to its antimineralocorticoid activity, drospirenone increases natriuresis, decreases water retention and blood pressure, and produces compensatory increases in plasma renin activity as well as circulating levels and urinary excretion of aldosterone. This has been shown to occur at doses of 2 to 4 mg/day. Similar effects occur during the luteal phase of the menstrual cycle due to increased progesterone levels and the resulting antagonism of the MR. Estrogens, particularly ethinylestradiol, activate liver production of angiotensinogen and increase levels of angiotensinogen and angiotensin II, thereby activating the renin–angiotensin–aldosterone system.
Androgenic progestins like levonorgestrel have been found to inhibit the procoagulatory effects of estrogens like ethinylestradiol on hepatic synthesis of coagulation factors, whereas this may occur less or not at all with weakly androgenic progestins like desogestrel and antiandrogenic progestins like drospirenone. Other activity
Drospirenone stimulates the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1). Certain other progestins act similarly in this assay, whereas progesterone acts neutrally. It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies. Pharmacokinetics
Absorption
The oral bioavailability of drospirenone is between 66 and 85%. Peak levels occur 1 to 6 hours after an oral dose. Levels are about 27 ng/mL after a single 4 mg dose. There is 1.5- to 2-fold accumulation in drospirenone levels with continuous administration, with steady-state levels of drospirenone achieved after 7 to 10 days of administration. Peak levels of drospirenone at steady state with 4 mg/day drospirenone are about 41 ng/mL. With the combination of 30 μg/day ethinylestradiol and 3 mg/day drospirenone, peak levels of drospirenone after a single dose are 35 ng/mL, and levels at steady state are 60 to 87 ng/mL at peak and 20 to 25 ng/mL at trough. The pharmacokinetics of oral drospirenone are linear with a single dose across a dose range of 1 to 10 mg. Intake of drospirenone with food does not influence the absorption of drospirenone.