Intestinal absorption and biliary excretion kinetics of 14C-labeled methadone in the rat

Intestinal abosrption, biliary excretion and enterohepatic circulation of d,l-methadone were studied in male, female, fasted and fed rats by monitoring the appearance of radioactivity in the portal vein, the inferior vena cava, and the bile following intraduodenal administration of 2-14C-d,l-methadone. An early peak in portal concentration was not reflected in the peripheral blood or in the bile. An enterohepatic circulation exists, but is minimal, accounting for less than 1% of the dose in the first hr. Experimental diversion of the bile flow from the lumen of the duodenum has little effect on the relative percentage of methadone vs. metabolites circulating in the blood. However, bile diversion was associated with a 2 to 3 fold increase in the concentration of methadone and its metabolites in portal and peripheral blood 30 min following administration. Eighty to 90% of the 14C in the portal blood is present as methadone and 60 to 70% of the 14C in peripheral blood is methadone while less than 10% of the radioactive materials in the bile is methadone. The amount of metabolite No. 1, metabolite No. 2 and water soluble metabolites vary with over 60% of the radioactive compounds in recirculated bile in the form of water soluble materials.