Almog S, Shafran N, Halkin H, Weiss P, Farfel Z, Martinowitz U, Bank H
Eur J Clin Pharmacol. 1985;28(3):257-61. doi: 10.1007/BF00543320.
Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25-30% of control and its kinetics were compared to those in 20 control patients who received warfarin alone. Potentiation occurred in 28/30 patients, presenting as a 35%-65% reduction in the required dose of warfarin, and was correlated with the dose of amiodarone (r = 0.77, p less than 0.01). The free warfarin fraction was not affected by amiodarone (1.8% vs 1.6% in the controls). Warfarin clearance was lower in amiodarone-treated patients than in the controls (1.4 vs 3.1 ml/min, p less than 0.01) with similar plasma concentrations (1.5 vs 1.2 micrograms/ml) despite administration of lower doses (23.3 vs 39 mg/week respectively). The amiodarone concentration was significantly correlated with the warfarin concentrations independent of the effect of amiodarone on the dose of warfarin. Amiodarone hat no effect on prothrombin other than through its actions on the dose and plasma concentration of warfarin. The mechanism of the amiodarone-warfarin interaction is pharmacokinetic through dose - and concentration - dependent inhibition of warfarin elimination.
在30例患者中研究了胺碘酮对华法林抗凝作用的增强效果。13例患者同时接受两种药物治疗，17例患者先单独接受华法林治疗，之后再接受联合治疗。调整华法林剂量以维持凝血酶原时间在对照值的25%-30%之间，并将其动力学与20例单独接受华法林治疗的对照患者进行比较。30例患者中有28例出现增强效果，表现为华法林所需剂量降低35%-65%，且与胺碘酮剂量相关（r = 0.77，p<0.01）。游离华法林分数不受胺碘酮影响（分别为1.8%和1.6%）。尽管胺碘酮治疗组患者华法林剂量较低（分别为23.3mg/周和39mg/周），但与对照组相比，其清除率更低（1.4 vs 3.1ml/min，p<0.01），而血浆浓度相似（1.5 vs 1.2μg/ml）。胺碘酮浓度与华法林浓度显著相关，且与胺碘酮对华法林剂量的影响无关。胺碘酮除了通过影响华法林的剂量和血浆浓度外，对凝血酶原无影响。胺碘酮-华法林相互作用的机制是通过剂量和浓度依赖性抑制华法林消除的药代动力学机制。
