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

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.