Positive inotropic effects of digitoxin- and digoxin-glucuronide in human isolated ventricular heart muscle preparations.
The effect on force of contraction of human isolated ventricular heart muscle preparations was studied with the 16'-glucuronides of digitoxin (dt-gluc) and digoxin (dg-gluc). The parent compounds digitoxin (dt) and digoxin (dg) were studied for comparison and all compounds were also investigated in guinea-pig isolated papillary muscles. All compounds increased myocardial force of contraction in human preparations in a concentration-dependent manner. The positive inotropic effect of dt-gluc and dg-gluc began at 0.1 mumol 1(-1) and was maximal at 1 mumol 1(-1). The metabolites were slightly less potent but, on the other hand, slightly more effective than the parent compounds dt and dg. The positive inotropic effects of all compounds peaked after about 60 minutes. In contrast, the decline of the positive inotropic effect upon washing was about twice as fast in the case of the hydrophilic metabolites. Similar results were obtained in guinea-pig papillary muscles. It is concluded that the glucuronides of digitoxin and digoxin are biologically active in the human heart. This may be of clinical importance with respect to the positive inotropic action and the plasma level determination of the cardiac glycosides.
D000818:Animals; D004074:Digitoxin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004077:Digoxin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008658:Inactivation, Metabolic; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship
C041763:digoxin-16'-glucuronide; C041766:digitoxin-16'-glucuronide; D004077:Digoxin; D004074:Digitoxin