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Biliary excretion of Δ1-tetrahydrocannabinol and its metabolites in the rat

1974; Elsevier BV; Volume: 23; Issue: 7 Linguagem: Inglês

10.1016/0006-2952(74)90290-1

1873-2968

Marianne Widman, Marianne Nordqvist, Stig Agurell, Jan‐Erik Lindgren, Finn Sandberg,

Alcohol Consumption and Health Effects

Δ1-Tetrahydrocannabinol (Δ1-THC) administered i.v. (1 mg/kg) to anaesthetized rats with cannulated bile ducts is rapidly eliminated as metabolites in the bile. 60–70 per cent in 6 hr. In comparison with the slow excretion via faeces an extensive enterohepatic circulation, which may be of toxicological importance, is indicated. Unchanged Δ1-THC and cannabinol are eliminated in low amounts (0.05 0.1 percent) in the bile. A few per cent consists of two or more mono-oxygenated metabolites. neither of which is identical with 7-hydroxy-Δ1-THC or 6-β-hydroxy-Δ1-THC. The main part of the non-conjugated metabolites is present as compounds more polar than 7-hydroxy-Δ1-THC and as carboxylic acids. These acids were more polar than Δ1-THC-7-oic acid which could not be identified in a free or conjugated form. In the rat about 60 per cent of the metabolites are eliminated as water-soluble conjugates. Hydrolysis with glucuronidase liberated aglycones which were mainly neutral whereas hydrolysis with alkali released neutral but also some acidic compounds. 7-Hydroxy-Δ1-THC was identified as an aglycone of glucuronic acid and furthermore, three mono-oxygenated cannabinoids were isolated after hydrolysis and partially characterized.