Absorption, Distribution, Excretion and Metabolism of SC-11800EE, a Combined Steroid Preparation of SC-11800 (ethynodiol diacetate) and Ethinyl Estradiol in Rats and Mice

Abstract

Absorption, distribution, excretion and metabolism of SC-11800EE, a combined steroid preparation consisting of SC-11800 (ethynodiol diacetate) as gestagen and ethinyl estradiol (EE) as estrogen in 20: 1 (w: w), were studied with the use of ¹⁴C-SC-11800 and ₃H-EE by radiometry in female rats and by the whole body autoradiography in female normal and pregnant mice.
The gestagen orally given with EE was rapidly absorbed from digestive tracts and distributed in tissues in various levels. Gestagen levels in liver and kidney exceeded that in plasma. About 75% of dosed radioactivity was excreted in feces largely via bile and more than 20% in urine within 72 hr after administration. The gestagen was metabolized extensively to more polar products and their conjugates. The pharmacokinetic behavior of the gestagen given with EE did not alter after repeated administrations for 7 days, but was slightly different from that without EE, possibly due to the estrogen effect. The pharmacokinetic behavior o f the estrogen was independent from the gestagen given simultaneously.
The distribution of the gestagen given with EE revealed by the whole body autoradiography in normal mice were essentially consistent with the radiometric results in rats and that in the pregnant mice showed that the gestagen in fetus was virtually nil under the present conditions.