EFFECT OF CLARITHROMYCIN ON RENAL EXCRETION OF DIGOXIN - INTERACTION WITH P-GLYCOPROTEIN

Citation
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
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
0009-9236
Volume
64
Issue
1
Year of publication
1998
Pages
123 - 128
Database
ISI
SICI code
0009-9236(1998)64:1<123:EOCORE>2.0.ZU;2-V
Abstract
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.