Biomol Ther.  2016 Jul;24(4):446-452. 10.4062/biomolther.2015.197.

Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

• Noh K
• Oh DG
• Nepal MR
• Jeong KS
• Choi Y
• Kang MJ
• Kang W
• Jeong HG
• Jeong TC

• KMID: 2351695
• DOI: http://doi.org/10.4062/biomolther.2015.197

Abstract

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

Keyword

Chrysin; Caffeine; Drug interaction; Pharmacokinetics; in vivo

MeSH Terms

Animals
Biological Availability
Caffeine*
Cytochrome P-450 CYP1A1
Drug Interactions
Honey
Humans
In Vitro Techniques
Male
Metabolism
Microsomes, Liver
Pharmacokinetics
Plasma
Propolis
Rats*
Rats, Sprague-Dawley
Theobromine
Caffeine
Cytochrome P-450 CYP1A1
Propolis
Theobromine