Lack of interaction between digoxin and quinidine in cultured heart cells

Journal Article · Mon Mar 01 04:00:00 EST 1982 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5335645

Horowitz, J D; Barry, W H; Smith, T W

Previous investigations have raised the possibility that the digoxin-quinidine interaction is associated with a reduction in the positive inotropic effect of digoxin due to displacement of digoxin from cardiac as well as skeletal muscle. To circumvent some of the complexities presented by intact animal models, this interaction was investigated in cultured chick embryo ventricular cells. Quinidine, even at relatively high concentrations (10(-4)--2 x 10(-3) M), did not significantly affect positive inotropic effects of digoxin and did not protect against cellular contracture induced by toxic digoxin concentrations, despite preincubation of cells with quinidine for 60 min. The effects of digoxin on monovalent cation transport, as judged by active uptake of the K analog 86Rb, were also not altered by 10(-4) M to 2 x 10(-3) M quinidine. These data suggest that quinidine does not displace digoxin from Na, K adenosine triphosphatase binding sites in this preparation. Although these data must be extrapolated to the intact animal with caution, our findings suggest that changes in digoxin clearance are more likely of primary importance in the digoxin-quinidine interaction, and indicate that the approximately 2-fold increase in serum digoxin concentration observed after addition of quinidine would be expected to have direct effects on myocardial cells comparable with those seen with increased digoxin concentration in the absence of quinidine.

• Research Organization: Cardiovascular Division, Brigham and Women's Hospital and Departments of Medicine, Boston Massachusetts
• OSTI ID: 5335645
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 220:3; ISSN JPETA
• Country of Publication: United States
• Language: English

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551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIRDS
BODY
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CELL CULTURES
CHICKENS
DAYS LIVING RADIOISOTOPES
DIGITALIS GLYCOSIDES
DIGOXIN
DRUGS
EMBRYONIC CELLS
FOWL
GLYCOSIDES
HEART
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MINUTES LIVING RADIOISOTOPES
MUSCLES
MYOCARDIUM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
RUBIDIUM 86
RUBIDIUM ISOTOPES
SYNERGISM
UPTAKE
VERTEBRATES