New kinetic data on estradiol in light of the vaginal ring concept.
The principal estrogen produced by the functioning premenopausal ovary is 17 beta-estradiol. At the point of irreversible ovarian failure, at menopause, the production of estradiol decreases dramatically, which results in circulating serum levels less than 120 pmol/l. It is important to recognise the pharmacokinetic and metabolic outcomes associated with dosage and route of delivery of estrogen. One of the most promising methods of administering estrogen replacement therapy (ERT) for local effects is the estradiol vaginal ring designed for a controlled continuous low release (7.5 micrograms estradiol/24 h) over a period of 90 days. The present study was undertaken to characterise the basal endogenous turnover of estradiol in postmenopausal women. Information on the disposition of estradiol after an intravenous dose formed the base of the kinetic model. The rate of extent of absorption of estradiol was assessed after ring application. Individual serum concentrations of estradiol were analysed without subtraction of the basal estradiol levels. The results indicate a rapidly eliminated compound (plasma clearance 2 l/min) with a distribution of approximately 50 l, resulting in an efficient half-life of about 20 min. The endogenous production was highly variable (< 1-44 micrograms/24 h). The steady-state estradiol levels following ring application did not increase and were well within the normal basal estradiol range seen in untreated women. In light of the present findings, the low daily dose, the low availability of estradiol across the vaginal wall and the controlled local delivery, favour the use of the estradiol vaginal ring.
Gabrielsson
J
J
Department of Drug Disposition, Uppsala, Sweden.
Wallenbeck
I
I
Larsson
G
G
Birgerson
L
L
Heimer
G
G
D000282:Administration, Intravaginal; D001682:Biological Availability; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D017698:Postmenopause
D004958:Estradiol