Pharmacokinetics of estradiol
Estradiol can be administered in the form of a very long-lasting subcutaneous pellet implant. These implants are replaced once every 6 to 12 months, and can achieve high and very constant circulating levels of estradiol. They are surgically inserted by a trained physician in a medical office or clinic and can be placed into locations including the lower abdomen, lower back, buttocks, or hips. Subcutaneous implants containing 25, 50, and 100 mg estradiol for replacement usually once every 6 months are available as approved pharmaceutical medications. Up to 800 mg estradiol per implantation has been used. Pharmaceutical estradiol implants have been said to be used almost exclusively in the United Kingdom. An estradiol implant has not been approved by the FDA as a pharmaceutical medication in the United States, but hormone implants, including estradiol implants, are available as custom compounded products in this country.
EC508
EC508, also known as estradiol 17β-(1-(4-(aminosulfonyl)benzoyl)--proline), is an estrogen which is under development by Evestra for use in menopausal hormone therapy and as a hormonal contraceptive for the prevention of pregnancy in women. It is an orally active estrogen ester – specifically, a C17β sulfonamide–proline ester of the natural and bioidentical estrogen estradiol – and acts as a prodrug of estradiol in the body. However, unlike oral estradiol and conventional oral estradiol esters such as estradiol valerate, EC508 undergoes little or no first-pass metabolism, has high oral bioavailability, and does not have disproportionate estrogenic effects in the liver. As such, it has a variety of desirable advantages over oral estradiol, similarly to parenteral estradiol, but with the convenience of oral administration. EC508 is a candidate with the potential to replace not only estradiol in clinical practice, but also ethinylestradiol in oral contraceptives. Evestra intends to seek Investigational New Drug status for EC508 in the second quarter of 2018.