Metabolism of the Hydroxyethylrutosides III. The Fate of Orally Administered Hydroxyethylrutosides in Laboratory Animals; Metabolism by Rat Intestinal Microflora in vitro

Abstract

1. The absorption, metabolism and excretion of hydroxyethylrutosides in rat and other mammals have been studied. Following oral administration to rats of 3′,4′,7-tri-O-(β-hydroxyethyl)rutoside, 4′,7-di-O-(β-hydroxyethyl)ruto-side and 7-O-(β-hydroxyethyl)rutoside, significant levels of the administered compounds and their conjugates in bile were observed, but 3′,4′,5,7-tetra-O-(β-hydroxyethyl)rutoside was poorly absorbed. The major portion of the dose of each rutoside was excreted as the aglycone in faeces. Urinary excretion of all rutosides was low.

2. Levels of excretion of ¹⁴C in the urine of rabbits and rhesus monkeys given 3′,4′,7-tri-O-(β-hydroxy[¹⁴C₂]ethyl)rutoside and 3′,4′,5,7-tetra-O-(β-hydroxy[¹⁴C₂]ethyl)rutoside were similar (<2.5% of dose) to those observed in the rat.

3. The hydroxyethylrutosides and rutin are degraded to their aglycones by the rat intestinal microflora both in vivo and in vitro. The B rings of rutin and 7-O-(β-hydroxyethyl)rutoside give rise to the same phenolic acid metabolites. Mono-O-(β-hydroxyethyl)phloroglucinol is formed from the A ring of 7-O-(β-hydroxyethyl)rutoside. Excretion of these metabolites in urine is suppressed by concurrent administration of neomycin.

4. 3′,4′,7-Tri-O-(β-hydrcxyethyl)rutoside did not undergo cleavage to metabolites other than the aglycone after continuous administration to rats for periods of up to 5 months.