PMID: 40771Sep 1, 1979

Role of enterohepatic circulation in the analgesic action of 1-alpha-acetylmethadol in the rat

Drug Metabolism and Disposition : the Biological Fate of Chemicals
D L RoerigR I Wang


The enterohepatic circulation of 1-alpha-acetylmethadol (LAAM) was investigated in the rat. Bile containing 3H-LAAM metabolites was collected from a biliary cannulated donor rat after administration of 3H-LAAM (5 mg/kg, 15 muCi/kg, sc) and infused into the intestine of a double biliary-cannulated recipient rat for 1 hr, and tritium excreted into the bile of the recipient rat was monitored. Within 1 hr after the end of infusion significant radioactivity was found in the bile of the recipient rat and by 10 hr 50% of the infused dose of 3H had been re-excreted into bile. The contribution of enterohepatic circulation of LAAM metabolites to the analgesic action of LAAM was also assessed. Pretreatment of rats with neomycin sulfate was used as a method of decreasing enterohepatic circulation of biliary glucuronide conjugates of LAAM metabolites, and such pretreatment had no effect on LAAM analgesia (6 mg/kg) measured by the hot-plate method. In rats with a biliary fistula, a situation in which enterohepatic circulation was completely eliminated, the analgesic response to a dose of LAAM (6 mg/kg, sc) was not different from sham-operated control group. The above findings indicate that enterohepatic circulation of LAAM metabolites does n...Continue Reading

Related Concepts

Salicylhydroxamic acid
Reaction Time
Neomycin Palmitate
Absence of Pain Sensation
Levomethadyl Acetate Hydrochloride
Intestinal Wall Tissue
Analgesic brand of acetaminophen-phenyltoloxamine
Enterohepatic Circulation

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