rather indirect evidence tends to indicate that absorption, metabolism, and excretion of 
orally administered stilbestrol probably is as rapid as the absorption of any ingested 
lipoid material. 
Information on the absorption of stilbestrol or other synthetic estrogens when 
administered to poultry by routes other than implantation are very fragmentary. Experi- 
ments involving the use of pastes, stilbestrol-coated sugar pellets, solutions of stilbestrol 
in oil, or oral administration of estrogens, have yielded no direct quantitative information 
concerning the rate or amount of absorption of the active compound, Indirect evidence of 
absorption, or lack of it, is usually obtained from physiological effects. It has been con- 
cluded by this type of reasoning that the estrogens are absorbed too quickly and that the 
estrogenic effects have been too transitory to produce useful commercial responses (21). 
Metabolism 
Virtually nothing is known about the metabolism of diethylstilbestrol by the tissues 
of the body. While the enzymatic metabolism of the natural estrogens has been studied 
extensively and a metabolic scheme proposed and verified in many aspects, the corre- 
sponding information concerning stilbestrol is not known. 
Pathways of excretion 
Some information is available concerning the pathways of excretion of diethylstil- 
bestrol. In nonruminants, the excretory products of stilbestrol have been determined. 
Three groups of workers have isolated and identified the conjugate of stilbestrol in 
rabbit urine as_ stilbestrol-mono-glucuronide (22,10,43). Hexestrol and dienestrol 
mono-glucuronides were also isolated. No evidence for the formation of an ethereal 
sulfate or mercapturic acid derivative was found. It therefore appears as if the main 
metabolic change of the three synthetic estrogens is conjugation with glucuronic acid 
without any change in the structure of the original compound. From 20 to 70 percent of 
the administered estrogen can be isolated in this conjugated form in the urine. Mitchell 
(26) using tritium labeled stilbestrol found that excretion in urine began within the first 
6 hours after feeding. Terminal excretion times for radioactivity in the bile and the urine 
indicated that the period required for elimination of stilbestrol from the tissues of steers 
is about 72 hours. Radioactivity was detectable in the feces until 132 hours. When 10 mg. 
stilbestrol per day was fed to a steer for 11 days, 28 percent was recovered in the feces 
and 18 percent was recovered in the urine. Seventy-three percent of the activity in the 
urine, and 90 percent of the activity in the bile was found to be present in a conjugated 
form. In the feces, however, 98 percent of the activity was present as the free compound, 
which might indicate hydrolysis by microbial action of the conjugate. The activity in the 
kidney and liver was also present in the free form, 67 and 100 percent, respectively. 
There have been a number of other reports on the relative amounts of stilbestrol 
recovered in the feces and/or urine after oral feeding. Rueber (29) found 44 percent of 
stilbestrol intake eliminated in the feces. Melampy et al. (23) recovered an average of 
63 percent in the urine and feces. Story, et al. (33) recovered 80 percent of orally admin- 
istered stilbestrol in lambs, 48 percent being found in the feces while 32 percent was 
recovered in the urine. 
The recent work of Glascock (11) using tritium labeled hexestrol in lambs and goats 
gives the most complete and most accurate information on excretion reported to date. In 
these experiments almost all of the administered activity was recovered. The bile was 
the major pathway of excretion. The next major route was the urine. The maximum blood 
level of circulating estrogen was reached 2 hours after injection when about 22 percent of 
the dose was present in the circulation. Complete clearance from the blood was achieved 
within 24 hours. The injected hexestrol rapidly passed into the excretory pathways. The 
intestinal contents plus bile and feces contained approximately 37 to 45 percent of the 
activity, and the urine 25 to 30 percent, 5 to 8 hours after injection. 
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