Horowitz J D, Barry W H, Smith T W
J Pharmacol Exp Ther. 1982 Mar;220(3):488-93.
Previous investigations have raised the possibility that the digoxin-quinidine interaction is associated with a reduction in the positive inotropic effect of digoxin due to displacement of digoxin from cardiac as well as skeletal muscle. To circumvent some of the complexities presented by intact animal models, this interaction was investigated in cultured chick embryo ventricular cells. Quinidine, even at relatively high concentrations (10(-4)--2 x 10(-3) M), did not significantly affect positive inotropic effects of digoxin and did not protect against cellular contracture induced by toxic digoxin concentrations, despite preincubation of cells with quinidine for 60 min. The effects of digoxin on monovalent cation transport, as judged by active uptake of the K analog 86Rb, were also not altered by 10(-4) M to 2 x 10(-3) M quinidine. These data suggest that quinidine does not displace digoxin from Na, K adenosine triphosphatase binding sites in this preparation. Although these data must be extrapolated to the intact animal with caution, our findings suggest that changes digoxin clearance are more likely of primary importance in the digoxin-quinidine interaction, and indicate that the approximately 2-fold increase in serum digoxin concentration observed after addition of quinidine would be expected to have direct effects on myocardial cells comparable with those seen with increased digoxin concentration in the absence of quinidine.
先前的研究提出了这样一种可能性，即地高辛 - 奎尼丁相互作用与地高辛正性肌力作用的降低有关，这是由于地高辛从心肌以及骨骼肌中被置换出来。为了规避完整动物模型所呈现的一些复杂性，在培养的鸡胚心室细胞中研究了这种相互作用。尽管将细胞与奎尼丁预孵育60分钟，但奎尼丁即使在相对较高的浓度（10⁻⁴ - 2×10⁻³ M）下，也不会显著影响地高辛的正性肌力作用，并且不能预防由中毒剂量的地高辛诱导的细胞挛缩。用地高辛对单价阳离子转运的影响（通过钾类似物⁸⁶Rb的主动摄取来判断），也不会被10⁻⁴ M至2×10⁻³ M的奎尼丁所改变。这些数据表明，在这种制剂中奎尼丁不会从钠钾三磷酸腺苷结合位点置换地高辛。尽管这些数据必须谨慎地外推至完整动物，但我们的研究结果表明，地高辛清除率的变化在地高辛 - 奎尼丁相互作用中更可能具有首要重要性，并且表明在添加奎尼丁后观察到的血清地高辛浓度大约增加2倍，预计会对心肌细胞产生与在没有奎尼丁时地高辛浓度增加所观察到的直接作用相当的影响。
