Pharmacodynamics<unk>  works by reversibly binding to the aromatase enzyme, and through competitive inhibition blocks the conversion of androgens to estrogens in peripheral (extragonadal) tissues. The medication has been found to achieve 96.7% to 97.3% inhibition of aromatase at a dosage of 1 mg/day and 98.1% inhibition of aromatase at a dosage of 10 mg/day in humans. As such, 1 mg/day is considered to be the minimal dosage required to achieve maximal suppression of aromatase with<unk> . This decrease in aromatase activity results in an at least 85% decrease in estradiol levels in postmenopausal women. Levels of corticosteroids and other adrenal steroids are unaffected by<unk> . Pharmacokinetics The bioavailability of<unk>  in humans is unknown, but it was found to be well-absorbed in animals. Absorption of<unk>  is linear over a dosage range of 1 to 20 mg/day in humans and does not change with repeated administration. Food does not significantly influence the extent of absorption of<unk> . Peak levels of<unk>  occur a median 3 hours after administration, but with a wide range of 2 to 12 hours. Steady-state levels of<unk>  are achieved within 7 to 10 days of continuous administration, with 3.5-fold accumulation. However, maximal suppression of estradiol levels occurs within 3 or 4 days of therapy. Active efflux of<unk>  by P-glycoprotein at the blood–brain barrier has been found to limit the central nervous system penetration of<unk>  in rodents, whereas this was not the case with letrozole and vorozole. As such,<unk>  may have peripheral selectivity in humans, although this has yet to be confirmed. In any case, estradiol is synthesized peripherally and readily crosses the blood–brain barrier, so<unk>  would still expected to reduce estradiol levels in the central nervous system to a certain degree. The plasma protein binding of<unk>  is 40%. The metabolism of<unk>  is by N-dealkylation, hydroxylation, and glucuronidation. Inhibition of aromatase is due to<unk>  itself rather than to metabolites, with the major circulating metabolite being inactive. The elimination half-life of<unk>  is 40 to 50 hours (1.7 to 2.1 days). This allows for convenient once-daily administration. The medication is eliminated predominantly by metabolism in the liver (83 to 85%) but also by residual excretion by the kidneys unchanged (11%).<unk>  is excreted primarily in urine but also to a lesser extent in feces.
Anastrozole
Tamoxifen
Letrozole
Endoxifen
Salvestrol
Norendoxifen
Goserelin
N-Desmethyltamoxifen