| Affiliation: | (1) School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People’s Republic of China;(2) Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People’s Republic of China;(3) Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100094, People’s Republic of China |
| Abstract: | Purpose 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-β-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 μM of B was perfused through different sections of rat small intestine.Conclusion The first-pass metabolism of B in small intestine may play an important role in its low oral bioavailability. |
