Pharmacokinetic data on estradiol in light of the estring concept. Estradiol and estring pharmacokinetics.
The pharmacokinetics and pharmacodynamics of estradiol in humans are briefly reviewed in this paper. The estradiol vaginal ring was designed and developed to obtain controlled local delivery of very low doses of estradiol resulting in a marginal effect on plasma concentrations of estradiol, associated with a margin of safety over a prolonged period of time. Three clinical studies in postmenopausal women with signs and symptoms while plasma levels remain virtually unchanged in the lower part of the normal postmenopausal range. No pharmacodynamic effects of estrogen could be detected, reflecting a very low systemic exposure. The estradiol exposure and the plasma concentration time course during treatment with first and second ring during first month of the intended three month treatment period are compared. The very low systemic exposure is discussed in relation to existing therapies. Ongoing pharmacokinetic work with estradiol vaginal ring is briefly described. It is concluded that the estradiol vaginal ring is a very stable alternative to existing vaginal therapies, resulting in a very low systemic exposure to estradiol, and is associated with a minimal risk of drug interaction and has a high margin of safety.
Gabrielsson
J
J
Department of Pharmacokinetics and Drug Metabolism, ASTRA ARCUS AB, Södertalje, Sweden.
Wallenbeck
I
I
Birgerson
L
L
D000287:Administration, Topical; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism; D014621:Vagina / Q000187:drug effects*
D004958:Estradiol