Fat Storage,De-etherification and Elimination of Quinestrol in the Rat as Influenced by Route of Administration

Abstract

Summary

The influences of dose level and route of administration on fat storage and excretion of ethynylestradiol-3-cyclopentyl ether (EECPE) were studied in rats. The EECPE was tagged with ³H in the steroid nucleus and with ¹⁴C in the cyclopentyl group in order to be able to trace the de-etherification process. Over a range of oral doses of 20 μg to 12.5 mg, there was a proportional increase in the concentration of compound in body fat and brain. The storage increment exceeded the dose increment suggesting that with increasing dose more of the compound escaped metabolic alteration. Nearly twice as much radioactivity was found in fat, brain, and blood of rats in which EECPE had been injected parenterally (iv, ip, sc) rather than administered orally. Evidence was sought but not found that EECPE is metabolized by the gastrointestinal tract; in fact, orally and intravenously administered EECPE were excreted in qualitatively similar patterns in bile and urine. Excretion of radioactivity following treatment of rats with cyclopentanol-¹⁴C led to the conclusion that EECPE follows two basic metabolic pathways: (i) de-etherification with urinary excretion of cyclopentanol derivatives; and (ii) conjugation and biliary excretion of metabolites in which the ether linkage is still intact.