Fenster P E, White N W, Hanson C D
J Am Coll Cardiol. 1985 Jan;5(1):108-12. doi: 10.1016/s0735-1097(85)80091-7.
Amiodarone is known to raise serum digoxin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction in 10 normal subjects. The pharmacokinetic variables for digoxin were determined after a 1.0 mg intravenous dose of digoxin in each subject, before and after oral amiodarone, 400 mg daily for 3 weeks. During amiodarone administration, systemic clearance of digoxin was reduced from 234 +/- 72 ml/min (mean +/- standard deviation) to 172 +/- 33 ml/min (p less than 0.01). This was due to reductions in both renal clearance (from 105 +/- 39 to 84 +/- 15 ml/min) (p less than 0.05) and nonrenal clearance (from 130 +/- 38 to 88 +/- 20 ml/min) (p less than 0.01). Digoxin half-life of elimination was prolonged from 34 +/- 13 to 40 +/- 16 hours (p less than 0.05). Digoxin volume of distribution was not significantly changed. Amiodarone caused a three- to fivefold increase in serum reverse triiodothyronine levels, but changes in thyroid function were not quantitatively related to the changes in digoxin pharmacokinetics. These alterations in digoxin pharmacokinetics produced by amiodarone explain the increase in serum digoxin level that has been observed when this drug combination has been used clinically.
已知胺碘酮会使血清地高辛水平升高。本研究旨在评估10名正常受试者中这种相互作用的药代动力学基础。在每位受试者静脉注射1.0毫克地高辛后，测定其地高辛的药代动力学变量，分别在口服胺碘酮前以及口服胺碘酮400毫克每日，持续3周后进行测定。在服用胺碘酮期间，地高辛的全身清除率从234±72毫升/分钟（平均值±标准差）降至172±33毫升/分钟（p＜0.01）。这是由于肾清除率（从105±39降至84±15毫升/分钟）（p＜0.05）和非肾清除率（从130±38降至88±20毫升/分钟）（p＜0.01）均降低所致。地高辛的消除半衰期从34±13小时延长至40±16小时（p＜0.05）。地高辛的分布容积无显著变化。胺碘酮使血清反三碘甲状腺原氨酸水平升高了三至五倍，但甲状腺功能的变化与地高辛药代动力学的变化在数量上并无关联。胺碘酮引起的地高辛药代动力学这些改变解释了在临床使用这种药物组合时所观察到的血清地高辛水平升高的现象。
