Enterohepatic recycling of phenolphthalein, morphine, lysergic acid diethylamide (LSD) and diphenylacetic acid in the rat Hydrolysis of glucuronic acid conjugates in the gut lumen
Xenobiotica January 1, 1980 Robert Parker, P. C. Hirom, P. Millburn 46 citations
In female Wistar albino rats, biliary elimination of phenolphthalein, morphine, LSD, and diphenylacetic acid occurred predominantly as glucuronides, with 90%, 45%, 75%, and 57% of injected doses eliminated in bile within three hours. Infusing this bile into the duodena of other rats showed enterohepatic circulation: 85%, 41%, 28%, and 66% of the infused conjugates were reabsorbed and re-excreted over 24 hours. Suppressing intestinal bacteria with antibiotics reduced recirculation to 22%, 8.6%, and 21% for phenolphthalein, morphine, and diphenylacetic acid glucuronides, but did not affect absorption of free aglycones. This demonstrates that bacterial beta-glucuronidase hydrolysis of glucuronides is essential for enterohepatic circulation. Intestinal absorption of released aglycones correlated with their lipid-solubility, measured by octan-1-ol:phosphate buffer partition ratios.