Pharmacokinetic Interaction of Chrysin with Caffeine in Rats.
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.
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Keumhan
K
Noh
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Do Gyeong
do G
Oh
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Mahesh Raj
MR
Nepal
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Ki Sun
KS
Jeong
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Yongjoo
Y
Choi
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Mi Jeong
MJ
Kang
College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Wonku
W
Kang
College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
Hye Gwang
HG
Jeong
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Tae Cheon
TC
Jeong
Caffeine; Chrysin; Drug interaction; Pharmacokinetics; in vivo