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.
Estradiol 3-saccharinylmethyl ether
Estradiol 3-saccharinylmethyl ether, or 3-"O"-(saccharinylmethyl)-17β-estradiol, is a synthetic estrogen and estrogen ether – specifically, the C3 saccharinylmethyl ether of estradiol – which was described in the mid-1990s and was never marketed. It is a prodrug of estradiol, and has been found to be 9-fold as potent as estradiol via the oral route in rats. Similarly, its bioavailability (16%) was 5-fold greater than that of estradiol via the oral route in rats, and the elimination half-life of estradiol released from the drug was 5- to 7-fold longer than that of regular estradiol. Conversely, when estradiol 3-saccharinylmethyl ether and estradiol were given intravenously in rats, there was no difference between them in terms of potency. "In vitro" studies revealed that saccarinylmethylestradiol is not hydrolyzed to estradiol enzymatically but rather is hydrolyzed chemically in biological media such as plasma, apparently dependent on the concentration of protein. Taken together, saccarinylmethylestradiol appears to be partially protected from first-pass metabolism in the liver and intestines with oral administration and shows greatly improved oral potency compared to estradiol.