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- W2075732664 abstract "Abstract Novel experimental and theoretical methods in evaluating the systemic bioavaliability of estrogens delivered via the vaginal route have been developed. The approaches were demonstrated for estrone and estradiol in the rhesus monkey. These newly developed techniques have made it possible to quantify first pass vaginal membrane metabolism for estrone and for estradiol and to distinguish this process from peripheral tissue metabolism. This was achieved by obtaining steady-state blood levels of the steroids and all significant metabolites resulting from identical zero-order infusion rates of the steroid by the vaginal and intravenous routes. Comparison of the blood levels gave rapid estimations of bioavailability. The modeling of the steady-state situation and quantification of the kinetic parameters were employed such that differences in blood levels from vaginal and intravenous drug infusion mirrored the membrane transport and metabolic events. Membrane metabolism of infused estrone and estradiol reduced the blood levels of these steroids by about 55 and 61%, respectively, of that expected in the absence of membrane metabolism. About 45% of vaginally administered estrone appeared directly in the blood as estrone and 9% as estradiol and 46% as total conjugates. The dominant route of membrane metabolism of estrone was estrone conjugation rather than reduction to estradiol. When estradiol was infused vaginally, 26% estradiol appeared in the blood and 35% as estrone and 39% as total conjugates; the dominant route of metabolism was the oxidation to estrone and not estradiol conjugation." @default.
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- W2075732664 date "1979-05-01" @default.
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- W2075732664 title "Vaginal drug absorption in the rhesus monkey: Bioavailability method and assessment of estrogens" @default.
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- W2075732664 doi "https://doi.org/10.1016/0378-5173(79)90022-x" @default.
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