Role of intestinal first-pass metabolism of baicalein in its absorption process.
OBJECTIVE
The aim of the present study was to investigate the role of intestinal first-pass metabolism of baicalein (B) in its absorption process.


METHODS
The intestinal absorption of B was characterized using Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model. In addition, preliminary metabolic kinetics of B was evaluated in both rat and human intestinal S9 fractions.


RESULTS
B was well absorbed and extensively metabolized to baicalin (BG), baicalein-7-O-beta-glucuronide, in rat intestinal perfusion model, whereas less extent of metabolism was observed in the Caco-2 cell monolayer model. Moreover, BG generated in the intestinal epithelium during the absorption of B also rapidly transported to both the apical side (the apical chamber of Caco-2 model and the perfusate of the intestinal perfusion model) as well as the basolateral side of the small intestine (the basal chamber of Caco-2 model and the mesenteric vein of the intestinal perfusion model). From the preliminary metabolic studies, it was found that a higher loading dose of B resulted in a less extent of metabolism in intestine. In addition, the extent of metabolism of B was similar in jejunum and ileum when 50 microM of B was perfused through different sections of rat small intestine.


CONCLUSIONS
The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability.
Zhang
Li
L
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.
Lin
Ge
G
Chang
Qi
Q
Zuo
Zhong
Z
D000818:Animals; D001682:Biological Availability; D001711:Biotransformation; D018938:Caco-2 Cells; D044950:Flavanones / Q000097:blood / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D044950:Flavanones; D005419:Flavonoids; C038044:baicalin; C006680:baicalein