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地高辛 - 奎尼丁相互作用:药代动力学评估

Digoxin-quinidine interaction Pharmacokinetic evaluation.

作者信息

Hager W D, Fenster P, Mayersohn M, Perrier D, Graves P, Marcus F I, Goldman S

出版信息

N Engl J Med. 1979 May 31;300(22):1238-41. doi: 10.1056/NEJM197905313002202.

Abstract

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.

摘要

最近的几份报告显示,当奎尼丁与地高辛同时给药时,地高辛的血浆浓度会升高;本研究旨在探讨6名受试者中这种地高辛-奎尼丁相互作用的药代动力学。地高辛的消除半衰期虽然存在个体差异,但在给予奎尼丁时并没有明显变化(42小时对44小时)。在有奎尼丁存在的情况下,其他药代动力学值大幅降低:全身清除率(从每千克每分钟3.08毫升降至1.96毫升)、肾清除率(从每千克每分钟1.64毫升降至1.09毫升)和分布容积(从每千克10.87升降至7.35升)。这些结果可能是由于奎尼丁将地高辛从组织中的结合位点置换出来,导致地高辛血浆浓度升高。地高辛肾清除率的降低也可能是由于奎尼丁抑制了地高辛的肾脏分泌。

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