Effect of quinidine on the tissue binding of digoxin in guinea-pigs

The mechanism of quinidine-induced decrease in the tissue distribution of digoxin to heart, liver and skeletal muscle has been examined in guinea-pigs. Quinidine, in the presence of adenosine-5′-triphosphate (ATP), inhibited the specific binding of digoxin in homogenates of heart, liver and muscle, while in the absence of ATP the inhibition was observed only in heart. The decrease in the tissue-to-plasma unbound concentration ratios (Kpu) of heart and muscle determined from in-vitro binding studies was comparable to that in the Kpu values observed in-vivo, while in liver it was not sufficient to account for the fall in Kpuin-vivo values. It is concluded that quinidine-induced decrease in the tissue distribution of digoxin in heart and muscle is due to inhibition of tissue binding of this drug, while that in liver could be partially attributed to the decrease in the tissue binding.