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Abstract
1. Biliary elimination in female Wistar albino rats 3h after i.p. injection of [3H]phenolphthalein, [3H]morphine, 14C-LSD and [14C]diphenylacetic acid was 90%, 45%, 75% and 57% respectively, predominantly as glucuronides.
2. Infusion of 3 h bile from the previous experiments into the duodena of bile-duct-cannulated animals demonstrated enterohepatic circulation, amounting in 24 h to 85%, 41%, 28% and 66% of the infused doses of the conjugates of phenolphthalein, morphine, LSD and diphenylacetic acid respectively.
3. Pretreatment with antibiotics to suppress intestinal microflora decreased this enterohepatic recirculation to 22%, 86% and 21% in 24h for phenolphthalein, morphine and diphenylacetic acid glucuronides respectively. Antibiotic pretreatment did not influence the absorption and re-excretion of infused doses of the free aglycones, thus demonstrating the importance of bacterial β-glucuronidase hydrolysis of the biliary conjugates.
4. The extent of intestinal absorption of the aglycones after bacterial β-glucuronidase hydrolysis of the conjugates is related to their lipid-solubility as estimated by octan-1-o1:0·1 M phosphate buffer partition ratios (P-values).
5. The persistence of compounds in the enterohepatic circulation is determined by the faecal and urinary elimination of the circulating compounds. Faecal elimination is governed by the extent of intestinal absorption of the circulating compounds, which is influenced by the efficacy of intestinal hydrolysis of the conjugates and the relative lipophilicity of the aglycones released.
