Amiodarone, verapamil, and quinidine do not affect equilibrium binding of digoxin.
The binding of [3H]digoxin to purified canine cardiac sarcolemmal vesicles was characterized. Scatchard analysis of saturation isotherms yielded linear plots with a maximal binding capacity of 174 +/- 31.9 pmol/mg, a dissociation constant of 31.7 +/- 4.59 nM, and a Hill coefficient of 0.947 +/- 0.02 (mean +/- SEM), suggesting that [3H]digoxin bound to a single class of sites. In contrast to their marked effect on steady-state serum digoxin levels when administered in combination, quinidine, verapamil, and amiodarone were without effect on equilibrium binding of [3H]digoxin. Thus, increased steady-state serum concentrations of digoxin resulting from combination therapy with these particular drugs probably will have cardiac effects that may increase the risk of digitoxicity to the patient.
Colvin
R A
RA
Department of Zoological and Biomedical Sciences, Ohio University College of Osteopathic Medicine, Athens 45701.
Ashavaid
T F
TF
Katz
A M
AM
Messineo
F C
FC
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D009206:Myocardium / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology*; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase; D014700:Verapamil / Q000494:pharmacology*
D011955:Receptors, Drug; C028996:cardiac glycoside receptors; D004077:Digoxin; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D011802:Quinidine; D000638:Amiodarone