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

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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.

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Acknowledgments

This study was supported by CUHK Direct Grants (CUHK 2040830 and CUHK 2041012).

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Authors and Affiliations

  1. School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People’s Republic of China

    Li Zhang, Qi Chang & Zhong Zuo

  2. Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People’s Republic of China

    Ge Lin

  3. Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100094, People’s Republic of China

    Qi Chang

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  1. Li Zhang
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Correspondence to Zhong Zuo.

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Zhang, L., Lin, G., Chang, Q. et al. Role of Intestinal First-Pass Metabolism of Baicalein in its Absorption Process. Pharm Res 22, 1050–1058 (2005). https://doi.org/10.1007/s11095-005-5303-7

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  • DOI: https://doi.org/10.1007/s11095-005-5303-7

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