Concentration-Dependent Effect of Naringin on Intestinal Absorption of β1-Adrenoceptor Antagonist Talinolol Mediated by P-Glycoprotein and Organic Anion Transporting Polypeptide (Oatp) View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-03

AUTHORS

Yoshiyuki Shirasaka, Yan Li, Yuta Shibue, Erika Kuraoka, Hildegard Spahn-Langguth, Yukio Kato, Peter Langguth, Ikumi Tamai

ABSTRACT

PURPOSE: The purpose of this study is to clarify the impact of P-gp and Oatp on intestinal absorption of the beta(1)-adrenoceptor antagonist talinolol. METHODS: P-gp-mediated transport was measured in LLC-PK1/MDR1 cells. Oatp-mediated uptake was evaluated with Xenopus oocytes expressing Oatp1a5. Rat intestinal permeability was measured by the in situ closed loop method. In vivo absorption was pharmacokinetically assessed by measuring plasma concentration after oral administration in rats. RESULTS: In LLC-PK1/MDR1 cells, the permeability of talinolol was markedly higher in the secretory direction than in the absorptive one. The uptake of talinolol by Xenopus oocytes expressing Oatp1a5 was significantly increased compared with that by water-injected oocytes. Naringin inhibited talinolol uptake by Oatp1a5 (IC (50) = 12.7 microM). The reported IC (50) value of naringin for P-gp-mediated transport of talinolol is approximately 2,000 microM. Rat intestinal permeability of talinolol was significantly decreased in the presence of 200 microM naringin, but was significantly increased by 2,000 microM naringin. Similar results were obtained in in vivo absorption studies in rats. CONCLUSION: The absorption behavior of talinolol can be explained by the involvement of both P-gp and Oatp, based on characterization of talinolol transport by Oatp1a5 and P-gp, and the effects of naringin. More... »

PAGES

560-567

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11095-008-9771-4

DOI

http://dx.doi.org/10.1007/s11095-008-9771-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030163133

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19002566


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