Evidence
for Enhanced Intestinal Absorption of Digoxin by
P-Glycoprotein Inhibitors
Hadi
Valizadeh1, Maryam Mehtari2 and
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:
Email:
pzakeri@tbzmed.ac.ir Tel: +98 (411)
339-2593; Fax: +98 (411) 334-4798
Received: 11 April 2011
Revised accepted:
19
October 2012
Tropical
Journal of Pharmaceutical Research, December 2012;
11(6):
939-945
http://dx.doi.org/10.4314/tjpr.v11i6.10
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
