Abstract

Studies were carried out to measure the relative rates of absorption of ¹⁴C-diethylstilbestrol (DES) and ¹⁴C-diethylstilbestrol glucuronide (DESG) from the intestines of 5- and 25-day-old rats. The disappearance of radioactivity was followed after the labeled compounds were placed in intestinal loops in vivo. Unconjugated DES was absorbed more rapidly than DESG in the small intestine. Very little hydrolysis of the DESG took place in the proximal intestine of 25-day-old animals or in the 5-day-old intestine. Bacterial β-glucuronidase rapidly hydrolyzed DESG to DES in the cecum of 25-day-old rats. The liberated DES was slowly absorbed from the cecum due to the presence of fecal material. It is suggested that, in spite of the rapid hydrolysis of glucuronide conjugates in the lower bowel of 25-day-old rats, the slower absorption of DES in this portion of the intestine may cause the drug to enter the enterohepatic circulation at a slow rate. The results obtained in 25-day-old animals support the concept that conjugate hydrolysis must occur prior to entrance of DES into the enterohepatic circulation. This may not be the case in newborns, however, since evidence was obtained in 5-day-old rats which indicated that DESG may be absorbed intact from the distal portion of the intestine. The pattern of the enterohepatic circulation, including the absorption and hydrolysis of glucuronide conjugates, apparently changes with development after birth.