Metabolism of the Hydroxyethylrutosides. II. Excretion and Metabolism of 3',4',7-Tri-O-(β-hydroxyethyl)rutoside and Related Compounds in Laboratory Animals after Parenteral Administration

Abstract

1. Following intravenous administration of 3',4',7-tri-O-(β-hydroxyethyl)-rutoside, 4'7-di-O-(β-hydroxyethyl)rutoside or 7-O-(β-hydroxyethyl)rutoside approximately two-thirds of the dose of each is excreted in the bile of cannulated rats in 24 h. Urinary excretion does not exceed 25% of the dose in this time. At doses up to 10 mg/kg, biliary excretion is maximal within 3 h, but at higher doses (40–100 mg/kg it is prolonged and variable. Intraperitoneal administration of these rutosides results in higher excretion in the bile. The hydroxyethylrutosides are excreted in bile and urine unchanged, and as glucuronide conjugates.

2. In non-cannulated rats the major route of excretion of 3',4',7-tri-O-(β-hydroxyethyl)-rutoside and 4'7-di-O-(β-hydroxyethyl)rutoside is via the faeces, as the corresponding aglycone. 7-O-(β-hydroxyethyl)rutoside is similarly metabolized to the aglycone, which is then degraded by intestinal microflora to a compound which is absorbed and excreted in urine.

3. Following intravenous administration of 3',4',7-tri-O-(β-hydroxyethyl)-rutoside to non-cannulated rabbits and rhesus monkeys, urinary excretion did not exceed 20% of the dose in 72 h. Between 13–16% of the glycoside was detected in the gall-bile of monkeys within 3 h of administration.