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Effect of clarithromycin on renal excretion of digoxin: Interaction with P‐glycoprotein
Author(s) -
Wakasugi Hiroko,
Yano Ikuko,
Ito Tatsuya,
Hashida Tohru,
Futami Takahiro,
Nohara Ryuji,
Sasayama Shigetake,
Inui Kenichi
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90030-3
Subject(s) - digoxin , clarithromycin , p glycoprotein , pharmacology , kidney , creatinine , chemistry , renal physiology , endocrinology , medicine , excretion , biochemistry , antibiotics , heart failure , multiple drug resistance , helicobacter pylori
We present a digoxin‐clarithromycin interaction in two patients in whom digoxin concentrations were unexpectedly increased. The ratio of renal 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 role in the renal secretion of digoxin, we hypothesized that clarithromycin decreases renal digoxin excretion by inhibiting P‐glycoprotein‐mediated 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 deoxyribonucleic acid. Clarithromycin inhibited the transcellular transport of digoxin from the basolateral to the apical side in a concentration‐dependent manner and concomitantly increased the cellular accumulation of digoxin. These results suggest that clarithromycin may inhibit the P‐glycoprotein‐mediated tubular secretion of digoxin, and this interaction mechanism may contribute to an increase in the serum digoxin concentration. Clinical Pharmacology & Therapeutics (1998) 64 , 123–128; doi: