P-GLYCOPROTEIN-MEDIATED RENAL TUBULAR SECRETION OF DIGOXIN - THE TOXICOLOGICAL SIGNIFICANCE OF THE URINE-BLOOD BARRIER MODEL

We provide direct evidence that verapamil inhibits active digoxin secr etion in renal tubular cells (LLC-PK1), and that verapamil increases c ellular accumulation of digoxin. These findings suggest that verapamil inhibits the digoxin active secretory transport at the apical membran es, supporting the theory that P-glycoprotein mediates digoxin secreti on in the renal tubular cells. Based on existing data on digoxin trans port, we present a hypothetical model for the renal handling of digoxi n, implying that P-glycoprotein functions as a driving mechanism of a unidirectional ''urine-blood'' barrier.