Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Evidence for Enhanced Intestinal Absorption of Digoxin by P-Glycoprotein Inhibitors

Hadi Valizadeh¹, Maryam Mehtari², Parvin Zakeri-Milani³

¹Research Center for Pharmaceutical Nanotechnology; ²Drug Applied Research Center; ³Liver and Gastrointestinal Diseases Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

For correspondence:- Parvin Zakeri-Milani Email: pzakeri@tbzmed.ac.ir Tel:+984113392593

Received: 11 April 2011 Accepted: 19 October 2012 Published: 13 December 2012

Citation: Valizadeh H, Mehtari M, Zakeri-Milani P. Evidence for Enhanced Intestinal Absorption of Digoxin by P-Glycoprotein Inhibitors. Trop J Pharm Res 2012; 11(6):939-945 doi: 10.4314/tjpr.v11i6.10

© 2012 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the influence of macrolides as P-glycoprotein inhibitors on the level of intestinal absorption of digoxin.

Methods: Jejunal segments of anaesthetized rats were cannulated and perfused by digoxin in phosphate buffered saline (PBS) at 37 °C in the presence or absence of macrolides (erythromycin and clarithromycin). Samples were obtained from outlet tubing at different time points and digoxin concentration assayed. The effective permeability of the drug was calculated after analyzing the samples using reverse-phase HPLC method.

Results: Digoxin effective permeability was in the range of 0.24 ± 0.02 ×10^-4 to 0.32 ± 0.06 ×10^-4 cm/sec for the control group. The macrolides significantly (p < 0.05) increased intestinal transport of digoxin, with digoxin in the presence of 150 μM of each macrolide in the range 0.42 ± 0.08 ×10^-4 to 0.52 ± 0.07 ×10^-4 cm/sec. However, no significant difference (p > 0.05) was observed between the effects of the two macrolides.

Conclusion: The probable explanation for digoxin-macrolide interaction is inhibition of intestinal P-glycoprotein-mediated efflux of digoxin which leads to increased digoxin intestinal absorption.

Keywords: Digoxin, Macrolides, Efflux, Intestinal permeability, P-glycoprotein