Abstract
Aim:
Imperialine is an effective compound in the traditional Chinese medicine chuanbeimu (Bulbus Fritillariae Cirrhosae) that has been used as antitussive/expectorant in a clinical setting. In this study we investigated the absorption characteristics of imperialine in intestinal segments based on an evaluation of its physicochemical properties.
Methods:
Caco-2 cells were used to examine uptake and transport of imperialine in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of imperialine. The amount of imperialine in the samples was quantified using LC-MS/MS.
Results:
The aqueous solubility and oil/water partition coefficient of imperialine were determined. This compound demonstrated a relatively weak alkalinity with a pKa of 8.467±0.028. In Caco-2 cells, the uptake of imperialine was increased with increasing pH in medium, but not affected by temperature. The apparent absorptive and secretive coefficient was (8.39±0.12)×10−6 cm/s and (7.78±0.09)×10−6 cm/s, respectively. Furthermore, neither the P-glycoprotein inhibitor verapamil nor Niemann-Pick C1-Like 1 transporter inhibitor ezetimibe affected the absorption and secretion of imperialine in vitro. The in situ intestinal perfusion study showed that the absorption parameters of imperialine varied in 4 intestinal segments (duodenum, jejunum, ileum and colon) with the highest ones in the colon, where a greater number of non-ionized form of imperialine was present.
Conclusion:
The intestinal absorptive characteristics of imperialine are closely related to its physicochemical properties. The passive membrane diffusion dominates the intestinal absorption of imperialine.
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Acknowledgements
We are grateful for support from the National Basic Research Program of China (No 2013CB932504) and the National Natural Science Foundation of China (No 81130060).
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Supplementary information is available at website of Acta Pharmacologica Sinica's website.
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Supplementary Information S1
Development and validation of the method detecting pKa (DOC 140 kb)
Supplementary Information S2
Stability of imperialine in cell test solution and SPIP test solution (DOC 43 kb)
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Lin, Q., Ling, Lq., Guo, L. et al. Intestinal absorption characteristics of imperialine: in vitro and in situ assessments. Acta Pharmacol Sin 36, 863–873 (2015). https://doi.org/10.1038/aps.2015.27
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DOI: https://doi.org/10.1038/aps.2015.27
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