Studies on the Metabolic Fate of (¹⁴C)-Labelled (±)-2,3-Dehydroemetine in the Rat

Abstract

1. After intravenous injection of (¹⁴C)-labelled (±)-2,3-dehydroemetine into bile-cannulated rats, 25% of the dose of radioactivity is excreted in bile and urine in the first 24 h after dosage. The cumulative percentage excreted 72 h after dosage is approx. 35%, and the radioactivity in the facces in 72 h accounts for 1% dose.

2. Thin-layer chromatographic analysis of radioactive bile samples revealed only a trace of unchanged 2,3-dehydroemetine in the bile. Hydrolysis of bile samples with β-glucuronidase or with 1 M-HCl released free 2,3-dehydroemetine from its conjugated form. A number of polar metabolites were also released by β-glucuronidase treatment. There did not appear to be any sulphate conjugates in the bile.

3. Corresponding analysis of the radioactive constituents of urine samples showed that free 2,3-dehydroemetine accounts for 30–40% of the urinary radioactivity. There are also a number of polar metabolites. On hydrolysis with β-glucuronidase or sulphatase the chromatographic profiles of the urines do not change significantly.

4. (±)-2,3-Dehydroemetine does not appear to be a substrate for the liver microsomal drug metabolizing enzymes.