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

Abstract Purpose  The purpose of this study is to clarify the impact of P-gp and Oatp on intestinal absorption of the β1-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 μM). The reported IC 50 value of naringin for P-gp-mediated transport of talinolol is approximately 2,000 μM. Rat intestinal permeability of talinolol was significantly decreased in the presence of 200 μM naringin, but was significantly increased by 2,000 μM 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. [ABSTRACT FROM AUTHOR]