Dietary polyphenols (-)-epicatechin and chrysin inhibit intestinal glucuronidation metabolism to increase drug absorption.
The effect of dietary polyphenols on the intestinal glucuronidation and absorption of a model phenolic drug, alpha-naphthol (alpha-NA), was studied in isolated rat small intestine. (-)-Epicatechin significantly inhibited the glucuronidation of alpha-NA. Chrysin, (-)-epigallocatechin galleate (EGCG), and quercetin decreased the rate of glucuronidation, although not significantly. Baicalin did not affect the glucuronidation. The rate of absorption of alpha-NA in the presence of these polyphenols also varied. The absorption clearance (CLabs) and the metabolic clearance (CLmet) were inversely correlated, and this relationship was well explained in the metabolic inhibition model with kinetic parameters (knowledge-based prediction) which characterizes the relationship between the CLabs and CLmet of alpha-NA (Biochim Biophys Acta 1998, 1425, 398.). These results indicate that the concomitant intake of some polyphenols can increase the absorption of a phenolic drug, and the effect is predictable. (-)-Epicatechin and chrysin are effective for the inhibition of glucuronidation and promotion of intestinal drug absorption.
Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Science (TUPLS), 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. mizuma@ps.toyaku.ac.jp
Takashi
T
Mizuma
Shoji
S
Awazu
D000818:Animals; D002392:Catechin / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009284:Naphthols / Q000493:pharmacokinetics; D010636:Phenols / Q000493:pharmacokinetics; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar
D005419:Flavonoids; D020719:Glucuronides; D009284:Naphthols; D010636:Phenols; D059808:Polyphenols; C029350:1-naphthol; C043561:chrysin; D002392:Catechin