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Drug Metab Dispos. 1989 May-Jun;17(3):248-54.

Nasal absorption and metabolism of progesterone and 17 beta-estradiol in the rat.

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  • 1College of Pharmacy, University of Kentucky, Lexington 40536-0082.


The utility of the nasal route for administration of progesterone and 17 beta-estradiol has been studied in rats. The results indicate that both steroids are rapidly absorbed from the nasal cavity. The bioavailability of 14C-radiolabeled progesterone administered nasally was found to be 100% of that of an iv dose. Also, the areas under the curve for the iv and nasal routes of administration were in each case directly proportional to the dose within the range studied (50-150 micrograms/rat). The bioavailability of progesterone after intraduodenal (id) administration was only 1.2% of that following an iv dose. Nasal administration of 17 beta-estradiol resulted in significantly higher blood levels than those observed following id administration. The nasal bioavailability of 17 beta-estradiol, calculated from the ratio of areas under the curve following nasal and iv administration, was 50%, 71%, and 84% for doses of 5, 10, and 20 micrograms per rat, respectively, compared with 2-5% via the id route for the same dose. The ratios of estrone to estradiol obtained after nasal administration of the different doses were lower than those obtained after id administration but higher than those obtained after iv administration, indicating that 17 beta-estradiol is oxidized to estrone in the nasal cavity and that the extent of oxidation is lower than that observed after id administration. The data also indicate that for both the iv and nasal routes of administration, estrone and estradiol constitute together 78% of the total unconjugated estrogens, whereas for the id route, these two steroids constitute 10-20% of the total unconjugated estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)

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