Estradiol (medication)
Estradiol is available in a variety of different formulations, including oral, intranasal, transdermal/topical, vaginal, injectable, and implantable preparations. An ester may be attached to one or both of the hydroxyl groups of estradiol to improve its oral bioavailability and/or duration of action with injection. Such modifications give rise to forms such as estradiol acetate (oral and vaginal), estradiol valerate (oral and injectable), estradiol cypionate (injectable), estradiol benzoate (injectable), estradiol undecylate (injectable), and polyestradiol phosphate (injectable; a polymerized ester of estradiol), which are all prodrugs of estradiol.
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.