Spironolactone pharmacokinetics and actions in the dog: Influence on the potential spironolactone-digoxin interaction

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1988

OSTI ID:5547717

Beck, B L

This study was designed to determine if administration of spironolactone to achieve steady-state concentrations to dogs at steady-state digoxin concentration resulted in an increased serum digoxin concentration in dogs. Serum digoxin concentration and AcS tolerance were measured in dogs at steady-state spironolactone-digoxin concentration to determine if an increase in serum digoxin concentration resulted from spironolactone administration and if this resulted in increased cardiac effects of digoxin. To determine if a spironolactone-digoxin interaction occurred at the canine myocardial digitalis receptor in vitro, the effects of spironolactone and its metabolites on Na{sup +},K{sup +}-ATPase activity and ({sup 3}H)ouabain binding were studied. Spironolactone, canrenone, or K{sup +} canrenoate did not inhibit canine myocardial K{sup +}-dependent MFPase activity or the concentration-response curve for digoxin inhibition of K{sup +}-dependent MFPase. In contrast, 0.1 mM spironolactone or canrenone competitively antagonized ({sup 3}H)ouabain binding to canine myocardium. Neither 0.24 {mu}M spironolactone, 0.59 {mu}M canrenone, or 1.27 {mu}M 7{alpha}-thiomethylspirolactone, concentrations of spironolactone and its metabolites found after a therapeutic dose of spironolactone in man, altered ({sup 3}H)ouabain binding to canine myocardium.

• Research Organization: Medical Coll. of Ohio, Toledo, OH (USA)
• OSTI ID: 5547717
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ANIMALS
ATP-ASE
BIOCHEMICAL REACTION KINETICS
BODY
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
DIGITALIS
DIGITALIS GLYCOSIDES
DIGOXIN
DIURETICS
DOGS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYME ACTIVITY
ENZYMES
GLYCOSIDES
HEART
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
KINETICS
MAGNOLIOPHYTA
MAGNOLIOPSIDA
MAMMALS
MEDICINAL PLANTS
MEMBRANE PROTEINS
MUSCLES
MYOCARDIUM
ORGANIC COMPOUNDS
ORGANS
OUABAIN
PHOSPHOHYDROLASES
PLANTS
PROTEINS
REACTION KINETICS
RECEPTORS
STEADY-STATE CONDITIONS
STROPHANTHINS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES