Alterations in P-glycoprotein transport may be the mechanism by which atorvastatin increases digoxin concentrations, say researchers from Parke-Davis, the US manufacturer of atorvastatin. Furthermore, such alterations may form the basis of "many unexplained digoxin drug interactions, as well as some interactions for which an alternate explanation has been proposed", they conclude (Journal of Clinical Pharmacology 2000;40:91).
In pharmacokinetic studies, concomitant administration of 80mg atorvastatin was found to increase plasma digoxin concentrations by 20 per cent, the researchers say. Doses of 10mg atorvastatin had no effect.
Digoxin is known to undergo intestinal secretion, mediated by P-glycoprotein, they say. Atorvastatin is a CYP3A4 substrate and many such compounds are also substrates for P-glycoprotein transport. The researchers suggest that the interaction between atorvastatin and digoxin is a result of inhibition of P-glycoprotein-mediated secretion in the intestine, leading to an increase in the extent of absorption.
The researchers comment that, among other statins, fluvastatin and simvastatin have been observed to elevate digoxin levels but pravastatin, lovastatin and cerivastatin have not. It is not known if these statins are substrates for P-glycoprotein, they say.