Biliary excretion, metabolism and enterohepatic circulation of buprenorphine

Abstract

1. After intramuscular administration of [³H]buprenorphine to rats, dogs, rhesus monkeys and one human volunteer, most of the dosed radioactivity was excreted in the faeces, indicating biliary excretion and a possible enterohepatic circulation of the drug in these species.

2. After intravenous administration of [³H]buprenorphine (100 μ/kg) to bile-duct cannulated rats, over 90% of the administered radioactivity was excreted in bile within 48 h after dosing.

3. The major drug-related component in rat bile was buprenorphine glucuronide. N-Dealkylated buprenorphine (again conjugated) was also present and a sex difference in the extent of N-dealkylation was apparent.

4. Intraduodenal infusion of rats with bile from rats dosed with [³H]buprenorphine produced a slow, although extensive, excretion of drug-related material in the bile of the recipient animals.