The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers.
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Woodland C, Verjee Z, Giesbrecht E, Koren G, Ito S
The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers.
J Pharmacol Exp Ther. 1997 Oct;283(1):39-45.
- PubMed ID
- 9336306 [ View in PubMed]
- Abstract
When propafenone is given with digoxin, digoxin serum concentrations increase. Although the digoxin-propafenone interaction is well known clinically, the mechanism by which propafenone interferes with digoxin elimination is unclear. To test the hypothesis that propafenone or one or both of its two major metabolites, 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP), inhibit the P-glycoprotein-mediated net renal tubular secretion of digoxin, we examined the transport of digoxin and the well-studied P-glycoprotein substrate vinblastine across confluent Madin-Darby canine kidney cell monolayers in the absence and presence of propafenone, 5-OHP and NDPP. Propafenone and its two major metabolites significantly inhibit the secretory flux of digoxin and vinblastine (propafenone > 5-OHP >> NDPP). Despite decreases in net transport, cellular digoxin accumulation did not decrease, suggesting that neither propafenone nor its metabolites prohibited digoxin from entering the cells at the basolateral side. NDPP, but not 5-OHP, was detected after 48 hr of incubation of the cells with propafenone alone. When the cells were incubated with propafenone or 5-OHP, apical accumulation of 5-OHP, but neither propafenone nor NDPP, against a concentration gradient was observed. These findings are consistent with the hypothesis that the digoxin-propafenone interaction results from the inhibition of the renal tubular transport of digoxin by propafenone and its metabolites. Our data suggest that propafenone is an inhibitor of P-glycoprotein, whereas 5-OHP is a possible substrate.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Propafenone P-glycoprotein 1 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcetyldigitoxinPropafenone The serum concentration of Acetyldigitoxin can be increased when it is combined with Propafenone. DeslanosidePropafenone The serum concentration of Deslanoside can be increased when it is combined with Propafenone. DigitoxinPropafenone The serum concentration of Digitoxin can be increased when it is combined with Propafenone. DigoxinPropafenone The serum concentration of Digoxin can be increased when it is combined with Propafenone. OuabainPropafenone The serum concentration of Ouabain can be increased when it is combined with Propafenone.