P-glycoprotein-mediated transport of digitoxin, α-methyldigoxin and β-acetyldigoxin

Abstract

Digoxin is a drug with a narrow therapeutic index, which is substrate of the ATP-dependent efflux pump P-glycoprotein. Increased or decreased digoxin plasma concentrations occur in humans due to inhibition or induction of this drug transporter in organs with excretory function such as small intestine, liver and kidneys. Whereas particle size, dissolution rate and lipophilic properties have been identified as determinants for absorption of digitalis glycosides, little is known about P-glycoprotein transport characteristics of digitalis glycosides such as digitoxin, α-methyldigoxin, β-acetyldigoxin and ouabain. Using polarized P-glycoprotein-expressing cell lines we therefore studied whether these compounds are substrates of P-glycoprotein.