Effect of erythromycin and clarithromycin on the intestinal transport of digoxin

Abstract

Objectives: The purpose of the study was determining the intestinal permeability of digoxin using the SPIP technique and a range of concentrations in rats and assessing the quantitative contribution of P-gp-mediated efflux in limiting the oral bioavailability of digoxin using erythromycin and clarithromycin as inhibitors of P-gp efflux transporter. Moreover the enhancing effects of the investigated macrolides on digoxin absorption were compared. Methods: The study was performed on jejunal segment of rat. The cannulated segment was perfused by drug solution and samples were obtained from outlet tubing and the remaining drug was assayed. A reverse-phase HPLC method was used for analysis of all samples. Results: Although there were no differences among the obtained permeability coefficients in different concentrations of digoxin, erythromycin and clarithromycin significantly increased the intestinal transport of digoxin (p<0.05). Moreover there was no significant difference between clarithromycin and erythromycin effects on digoxin absorption (P>0.05). Conclusion: At least part of interactions between digoxin and macrolide antibiotics occurs in absorption level. Digoxin can rightly be classified as a low solubility-high permeability Class II BCS drug and its absorption from oral formulations could be affected by erythromycin and clarithromycin. Therefore in dose adjustment for patients using both digoxin and erythromycin or clarithromycin, this important interaction must be considered.