H. Wakasugi et al., EFFECT OF CLARITHROMYCIN ON RENAL EXCRETION OF DIGOXIN - INTERACTION WITH P-GLYCOPROTEIN, Clinical pharmacology and therapeutics, 64(1), 1998, pp. 123-128
We present a digoxin-clarithromycin interaction in two patients in who
m digoxin concentrations were unexpectedly increased. The ratio of ren
al digoxin clearance to creatinine clearance in one patient was lower
during the concomitant administration of clarithromycin (0.64 and 0.73
) than that after cessation of clarithromycin administration (1.30 +/-
0.20; mean +/- SD), Because P-glycoprotein could play an important ro
le in the renal secretion of digoxin, we hypothesized that clarithromy
cin decreases renal digoxin excretion by inhibiting P-glycoprotein-med
iated transport. Digoxin transport was evaluated with use of a kidney
epithelial cell line, which expresses the human P-glycoprotein on the
apical membrane by transfection with MDR1 complementary deoxyribonucle
ic acid, Clarithromycin inhibited the transcellular transport of digox
in from the basolateral to the apical side in a concentration-dependen
t manner and concomitantly increased the cellular accumulation of digo
xin, These results suggest that clarithromycin may inhibit the P-glyco
protein-mediated tubular secretion of digoxin, and this interaction me
chanism may contribute to an increase in the serum digoxin concentrati
on.