Intranasal absorption of estropipate in the dog

Abstract

The utility of nasal route for administration of estropipate has been studied in dogs. Plasma levels of estrone (E1) and estradiol (E2) in male dogs were determined after intranasal spray, oral administration and intravenous injection of estropipate. Nasal spray of estropipate resulted in significant higher mean plasma peak concentrations and area under curve of estrone (two-fold higher) and estradiol (four-fold higher) compared with the other two routes. A rise in E2/E1 plasma concentration ratio near or above unity was observed beginning 15 min to 1 h after intranasal application. In vitro studies have observed a rapid enzymatic conversion of estropipate to estrone and estradiol in nasal tissue. Estrone and estradiol were interconverted in the nose, and the rate of conversion from estrone to estradiol was 2.5 times faster than that from estradiol to estrone. The presence of desulfatase, reductase and some oxidase in nasal tissue was demonstrated. This study has shown that the intranasal administration of estropipate may deliver a mixture of estrone, estradiol, estrone sulfate and other metabolite(s) across the nasal mucosa into systemic blood, and can be an effective delivery method for estrogen replacement therapy.