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. Distribution The distribution half-life of drospirenone is about 1.6 to 2 hours. The apparent volume of distribution of drospirenone is approximately 4 L/kg. The plasma protein binding of drospirenone is 95 to 97%. It is bound to albumin and 3 to 5% circulates freely or unbound. Drospirenone has no affinity for sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG), and hence is not bound by these plasma proteins in the circulation. Metabolism The metabolism of drospirenone is extensive. It is metabolized into the acid form of drospirenone by opening of its lactone ring. The medication is also metabolized by reduction of its double bond between the C4 and C5 positions and subsequent sulfation. The two major metabolites of drospirenone are drospirenone acid and 4,5-dihydrodrospirenone 3-sulfate, and are both formed independently of the cytochrome P450 system. Neither of these metabolites are known to be pharmacologically active. Drospirenone also undergoes oxidative metabolism by CYP3A4. Elimination Drospirenone is excreted in urine and feces, with slightly more excreted in feces than in urine. Only trace amounts of unchanged drospirenone can be found in