In vitro assessment of the digoxin-quinidine interaction using cultured human cells

Quinidine has been shown to decrease the distribution volume of digoxin. In an attempt to study this phenomenon in vitro, we assessed the effect of quinidine on digoxin binding to human keratinocytes. There was a significant decrease in binding caused by 27 μM quinidine (from 2,193 ± 304 cpm/10⁶ cells to 1,847 ± 277 cpm/10⁶ cells) (mean ± SD) (P < 0.005). The increment of quinidine concentration to 270 and 2700 μM produced a further decrease in digoxin binding to 1,541 ± 196 cpm/10⁶ cells and 1,254 ± 269 cpm/10⁶ cells, respectively (P < 0.005). The addition of 12 μM quinidine to 128 μM digoxin caused a significant reversal of the inhibition of ⁸⁶rubidium uptake by the keratinocytes caused by 128 μM digoxin alone (from 24,100 ± 1,918 to 29,263 ± 3,857 cpm/10⁶ cells; P < 0.005). Because the skin is the largest organ in the human body and since a significant proportion of the digoxin is bound to the skin, it is suggested that the keratinocytes participate in the reduction of digoxin distribution volume caused by quinidine. The ⁸⁶rubidium uptake studies indicate that quinidine displaces digoxin from its specific receptor, the enzyme Na⁺,K⁺ ATPase.