Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Vol. 11, No. 6, 2012, pp. 939-945
Bioline Code: pr12111
Full paper language: English
Document type: Research Article
Document available free of charge
Tropical Journal of Pharmaceutical Research, Vol. 11, No. 6, 2012, pp. 939-945
© Copyright 2012 - Tropical Journal of Pharmaceutical Research
Evidence for Enhanced Intestinal Absorption of Digoxin by P-Glycoprotein Inhibitors|
Valizade, Hadi; Mehtari, Maryam & Zakeri-Milani, Parvin
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 Pglycoprotein-
mediated efflux of digoxin which leads to increased digoxin intestinal absorption.
Digoxin, Macrolides, Efflux, Intestinal permeability, P-glycoprotein
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