Role of Intestinal First-Pass Metabolism of Baicalein in its Absorption Process

• DOI: 10.1007/s11095-005-5303-7
• Publication Date: 2005-07-19T02:18:21Z
• Authors: Li Zhang; Ge Lin; Qi Chang; Zhong Zuo
• Keywords: Flavonoids; Male; Biological Availability; In Vitro Techniques; Rats; Perfusion; Rats, Sprague-Dawley; 03 medical and health sciences; Jejunum; 0302 clinical medicine; Intestinal Absorption; Ileum; Flavanones; Animals; Humans; Caco-2 Cells; Biotransformation

The aim of the present study was to investigate the role of intestinal first-pass metabolism of baicalein (B) in its absorption process.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.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.The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability.