Comparison of the metabolism in dogs of estradiol-17β following its intravenous and oral administration

Abstract Estradiol-17β (estradiol) labeled with either [ 3 H] or [ 14 C], was administered either by the intravenous or by the oral route to normal female beagle dogs. Blood samples from peripheral and portal veins and lymph samples from the lymphatic duct were obtained at increasing time intervals and radioactivity as estrone, estradiol, estrone sulfate, estrone glucuronide and estradiol glucuronides measured. Following intravenous administration the disappearance of estradiol from the blood could be described as a function which was the sum of three exponentials. Radioactivity as estrone appeared rapidly and then disappeared in a manner quantitatively and qualitatively similar to estradiol. The major conjugates circulating were estrone and estradiol glucuronides; the sulfates appeared to be relatively minor components. Following oral administration (labeled estradiol in 20% ethanolic solution) radioactivity appeared rapidly, to reach peak levels in 3–16 min in the peripheral blood, as both estradiol and estrone. Although about 70% of the administered radioactivity appeared in the blood, only about 10% of that was absorbed as estradiol. Estrone and estradiol glucuronides made up the majority of the radioactivity in the peripheral blood. When we measured the radioactivity in the portal blood, it was apparent that conjugation occurred primarily in the intestinal wall and to a lesser extent in the liver. We were able to find measurable quantities of radioactivity as estrone, estradiol, their glucuronides and estrone sulfate in the lymph. Most of this radioactivity arose from the estradiol administered by the intravenous route and little estradiol was absorbed from the intestine via the lymph. The intestines appear to be responsible for most of the first pass metabolism, both conjugation and conversion to estrone, of estradiol administered via the gastrointestinal tract.