Pedersen K E, Dorph-Pedersen A, Hvidt S, Klitgaard N A, Nielsen-Kudsk F
Clin Pharmacol Ther. 1981 Sep;30(3):311-6. doi: 10.1038/clpt.1981.165.
To explore a possible interaction between digoxin and verapamil, a single-dose kinetic study of digoxin was performed and then repeated after 10 days of verapamil treatment in eight healthy subjects. Verapamil diminished the apparent central distribution volume of digoxin from 0.83 +/- 0.25 to 0.64 +2- 0.17 l/kg (P less than 0.05) and reduced total body clearance of digoxin from 3.28 +/- 0.58 to 2.15 +/- 0.66 ml/min/kg (P less than 0.001) by impairing both renal and extrarenal clearance. Biological digoxin half-life rose from 38.6 +/- 8.5 to 50.5 +/- 8.3 hr (P less than 0.005). Reduction of renal clearance of digoxin may be due to inhibition of tubular secretion. The underlying mechanisms of extrarenal interaction are not known, but impaired hepatic degradation of digoxin induced by verapamil should be considered.
为探究地高辛与维拉帕米之间可能的相互作用，对8名健康受试者进行了地高辛单剂量动力学研究，随后在维拉帕米治疗10天后重复该研究。维拉帕米使地高辛的表观中央分布容积从0.83±0.25降至0.64±0.17升/千克（P＜0.05），并通过损害肾清除率和肾外清除率，使地高辛的全身清除率从3.28±0.58降至2.15±0.66毫升/分钟/千克（P＜0.001）。地高辛的生物半衰期从38.6±8.5小时升至50.5±8.3小时（P＜0.005）。地高辛肾清除率降低可能是由于肾小管分泌受抑制。肾外相互作用的潜在机制尚不清楚，但应考虑维拉帕米诱导地高辛肝脏降解受损。
