1998
DOI: 10.1016/s0009-9236(98)90030-3
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Effect of clarithromycin on renal excretion of digoxin: Interaction with P-glycoprotein*

Abstract: 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 digox… Show more

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Cited by 184 publications
(126 citation statements)
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“…7,9,10 Interacting drugs that are used in a variety of cardiac disease states, including amiodarone, verapamil, quinidine, macrolides, itraconazole, and cyclosporine, have been demonstrated in in vitro studies to inhibit P-glycoprotein transport in renal tubular cells. [17][18][19][20][21] P-glycoprotein is a 170-kDa membrane efflux transport protein that is located in the liver, pancreas, kidney, colon, and jejunum. Its theoretical mechanism involves active transport of digoxin into the urine, which leads to decreased clearance in the presence of glycoprotein inhibitors.…”
Section: Discussionmentioning
confidence: 99%
“…7,9,10 Interacting drugs that are used in a variety of cardiac disease states, including amiodarone, verapamil, quinidine, macrolides, itraconazole, and cyclosporine, have been demonstrated in in vitro studies to inhibit P-glycoprotein transport in renal tubular cells. [17][18][19][20][21] P-glycoprotein is a 170-kDa membrane efflux transport protein that is located in the liver, pancreas, kidney, colon, and jejunum. Its theoretical mechanism involves active transport of digoxin into the urine, which leads to decreased clearance in the presence of glycoprotein inhibitors.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, concomitant administration with various drugs, including cyclosporin A, calcium channel blockers, macrolide antibiotics, and azole antifungal drugs elevates serum concentration of digoxin, at least in part, via renal tubular Pgp (Rodin and Johnson 1988;Wakasugi et al 1998). Considering these pharmacokinetic significances of renal Pgp, the expression levels and activity of Pgp in the kidney would be a key factor for the optimal dosage regimen of digoxin.…”
Section: Discussionmentioning
confidence: 99%
“…They enhance the antitumour activity of macrophages, natural killer-and CD8 cytotoxic T-cells, reduce neutrophil production of interleukin-8, and inhibit tumour necrosis factor-a and vascular endothelial growth factor activity (Aoki et al, 2005). Clarithromycin is a substrate of P-glycoprotein, induces apoptotic changes in tumour cells and exhibits antitumour activity in different murine cancer models (Wakasugi et al, 1998;Hamada et al, 2000). These preclinical data constitute the rationale for prospective clinical trials addressing the antineoplastic activity of macrolides.…”
mentioning
confidence: 99%