Fichtl B, Doering W, Seidel H
Int J Clin Pharmacol Ther Toxicol. 1983 May;21(5):229-33.
Quinidine has been reported to reduce clearance and the distribution volume of digoxin. Data are presented indicating that serum digoxin concentration (SDC) is increased throughout the coadministration of quinidine. This strongly suggests that the quinidine-induced reduction of digoxin clearance is the main mechanism underlying this drug interaction. It has been suggested that beside renal clearance quinidine also reduces non-renal clearance of digoxin. Direct evidence is provided by a study in patients with impaired renal function. Irrespective of the degree of renal impairment, quinidine increases SDC to about the same amount as found in patients with normal renal function. Since quinidine does not interfere with plasma protein binding of digoxin, this implies a decrease in non-renal clearance. In all patient groups the incidence of this drug interaction is rather high; however, pronounced interindividual differences occur as regards the extent of the increase in SDC. Regardless of the state of renal function careful monitoring of digitalized patients is mandatory once quinidine therapy is initiated. Since it may take a week or more until a new steady state is established in patients with impaired renal function, this period of close monitoring should be extended correspondingly.
据报道，奎尼丁会降低地高辛的清除率和分布容积。现有数据表明，在奎尼丁与地高辛合用期间，血清地高辛浓度（SDC）会升高。这有力地表明，奎尼丁引起的地高辛清除率降低是这种药物相互作用的主要机制。有人提出，除了肾脏清除率外，奎尼丁还会降低地高辛的非肾脏清除率。一项针对肾功能受损患者的研究提供了直接证据。无论肾功能损害程度如何，奎尼丁使SDC升高的幅度与肾功能正常患者相近。由于奎尼丁不干扰地高辛与血浆蛋白的结合，这意味着非肾脏清除率降低。在所有患者组中，这种药物相互作用的发生率都相当高；然而，SDC升高的程度存在明显的个体差异。一旦开始奎尼丁治疗，无论肾功能状态如何，对使用地高辛的患者进行仔细监测都是必要的。由于肾功能受损的患者可能需要一周或更长时间才能建立新的稳态，因此密切监测期应相应延长。
