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Assessment and modulation of phillyrin absorption by P-gp using Caco-2 cells and MDR1-MDCKII cells

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Abstract

The study was to investigate the absorption mechanism and transport modulation of phillyrin by P-gp in Caco-2 cells and MDR1-MDCKII cells. Three concentrations of phillyrin were tested in transport studies. The absorptive transports of phillyrin in the two cell models were not concentration-dependent which indicated passive diffusion as the dominating process in the test concentrations. The absorptive P app were 7.15, 6.39 and 10.03 × 10−6 cm s−1, respectively, for different concentrations (2.2, 4.8 and 8.4 μg ml−1) in Caco-2 cells. And the low absorptive P app was consistent with the low oral bioavailability of phillyrin observed in pharmacokinetic experiments. In transport inhibition experiment, the efflux inhibitors, verapamil and GF120918 can increase the absorption of phillyrin in Caco-2 cells which suggested the involvement of efflux transporters. In the further inhibition experiment in MDR1-MDCKII cells, the absorption was greatly increased and the efflux of phillyrin was competitively inhibited by verapamil and GF120918, which confirmed the involvement of P-gp in the efflux of phillyrin.

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Acknowledgments

We appreciate the assistance of Dr. Wang ling for cell culture technology. This project was supported by China Postdoctoral Science Foundation (No. 20100471662) and PhD Programs Foundation of Ministry of Education of China (No. 20105132120001).

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Authors and Affiliations

  1. Pharmacy College, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Road, Chengdu, 610075, People’s Republic of China

    Yun-Xia Li, Liang-Hong Ye & Cheng Peng

  2. The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Chengdu, 610075, People’s Republic of China

    Yun-Xia Li, Liang-Hong Ye & Cheng Peng

  3. State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, 610075, People’s Republic of China

    Yun-Xia Li, Liang-Hong Ye & Cheng Peng

  4. West China School of Pharmacy, Sichuan University, Chengdu, 610041, People’s Republic of China

    Xue-Hua Jiang

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  1. Yun-Xia Li
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  2. Liang-Hong Ye
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Correspondence to Cheng Peng.

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Li, YX., Ye, LH., Jiang, XH. et al. Assessment and modulation of phillyrin absorption by P-gp using Caco-2 cells and MDR1-MDCKII cells. Eur J Drug Metab Pharmacokinet 36, 41–47 (2011). https://doi.org/10.1007/s13318-011-0026-0

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  • DOI: https://doi.org/10.1007/s13318-011-0026-0

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