Effects of selected drugs on serum digoxin concentration in dogs

Abstract

The effects of quinidine, quinine, aspirin, ibuprofen, indomethacin and acetaminophen on steady state serum digoxin concentrations and total body digoxin clearance were studied in an animal model designed to simulate closely the clinical use of these drugs. When administered concurrently with digoxin, all of these drugs, with the exception of acetaminophen, caused a significant increase in serum digoxin concentration. Serum digoxin concentration was elevated (p <0.05) from 1.0 ± 0.14 to 2.06 ± 0.32 ng/ml with quinidine, from 0.70 ± 0.10 to 1.28 ± 0.20 ng/ml with quinine, from 1.12 ± 0.15 to 2.58 ± 0.24 ng/ml with aspirin, from 0.76 ± 0.08 to 1.1 ± 0.16 ng/ ml with indomethacin and from 0.90 ± 0.16 to 3.5 ± 0.65 ng/ ml with the largest dose of ibuprofen studied. Serum creatinine concentration was not elevated by administration of any of these drugs. The effects of aspirin and ibuprofen on serum digoxin concentration were directly related to the serum concentration of these drugs. The elevation in serum digoxin concentration produced by these drugs was due, at least in part, to a reduction in digoxin clearance. Digoxin clearance in the absence of any other treatment was 531 ± 34 ml/h per kg and was reduced ( p <0.05) to 352 ± 31,348 ± 39,462 ± 52 and 317 ± 56 ml/ h per kg by quinidine, quinine, aspirin and ibuprofen, respectively. Acetaminophen did not significantly alter the clearance of digoxin. These results clearly demonstrate that several commonly used drugs when administered concurrently with digoxin are capable of significantly elevating serum digoxin concentrations and thus may have the potential to increase the toxicity of this widely used cardiac glycoside. A drug-induced reduction in digoxin clearance appears likely to play an important role in increasing the serum digoxin concentration. Although these findings require confirmation in human beings, they suggest that caution should be used in administering large doses of nonsteroidal antiinflammatory drugs in conjunction with cardiac glycosides.