Kuhlmann J, Marcin S
Am Heart J. 1985 Dec;110(6):1245-50. doi: 10.1016/0002-8703(85)90021-3.
Investigations by various teams have shown that combined treatment with verapamil and digoxin may result in a marked increase in digoxin plasma concentrations, necessitating a reduction in the dose of digoxin. This is mainly due to an impairment of the renal digoxin excretion. Unlike digoxin, the excretion of digitoxin is independent of renal function. A prospective clinical study was therefore planned to investigate the influence of a daily dose of 240 mg of verapamil on pharmacokinetics and the cardiac effect of digitoxin after a single dose (n = 3) and under steady-state conditions (n = 10). While pretreatment with verapamil did not alter pharmacokinetics of digitoxin in the single-dose study, there was a slight rise of digitoxin plasma concentrations (an average of 35% in 8 out of 10 patients) following administration of verapamil for a period of 4 to 6 weeks. Renal excretion of digitoxin, however, was not changed significantly. Simultaneous with a rise of digitoxin plasma concentrations and until a new steady state was reached, PQ interval was prolonged and T wave flattening intensified. On the other hand, the antagonistic effect on contractility which was initially observed after verapamil administration was diminished. Based on these observations, it can be concluded that the risk of digitalis overdose after combined treatment with verapamil and digitoxin may be less pronounced than after digoxin, and that this glycoside can prove a valuable alternative.
多个团队的研究表明，维拉帕米与地高辛联合治疗可能会导致地高辛血浆浓度显著升高，因此需要减少地高辛的剂量。这主要是由于肾脏对地高辛排泄的损害。与地高辛不同，洋地黄毒苷的排泄与肾功能无关。因此，计划进行一项前瞻性临床研究，以调查每日剂量240mg维拉帕米对洋地黄毒苷单剂量（n = 3）和稳态条件下（n = 10）的药代动力学及心脏效应的影响。虽然在单剂量研究中，维拉帕米预处理未改变洋地黄毒苷的药代动力学，但在给予维拉帕米4至6周后，洋地黄毒苷血浆浓度略有升高（10名患者中有8名平均升高35%）。然而，洋地黄毒苷的肾脏排泄没有显著变化。随着洋地黄毒苷血浆浓度升高并直至达到新的稳态，PQ间期延长，T波平坦化加剧。另一方面，最初在给予维拉帕米后观察到的对收缩力的拮抗作用减弱。基于这些观察结果，可以得出结论，维拉帕米与洋地黄毒苷联合治疗后洋地黄中毒的风险可能比与地高辛联合治疗后要小，并且这种糖苷可能是一种有价值的替代药物。
