Testing the Pharmacokinetic Interactions of 24 Colonic Flavonoid Metabolites with Human Serum Albumin and Cytochrome P450 Enzymes
Abstract
Flavonoids are extensivelly metabolized. There are limited data on the pharmacokinetic interactions of their metabolites.
In this in vitro study, the interactions of 24 microbial flavonoid metabolites with human serum albumin and cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes was investigated. Some metabolites (e.g., 2,4-dihydroxyacetophenone, pyrogallol, O-desmethylangolensin, and 2-hydroxy-4-methoxybenzoic acid) form stable complexes with albumin.
However, the compounds tested did not considerably displace Site I and II marker drugs from albumin. All CYP isoforms examined were significantly inhibited by O-desmethylangolensin; nevertheless, only its effect on CYP2C9 seems to be relevant.
Furthermore, resorcinol and phloroglucinol showed strong inhibitory effects on CYP3A4. These results demonstrate that some colonic metabolites are able to interact with proteins involved in the pharmacokinetics of drugs.