Aberg G, Ronfeld R, Aberg L, Fitzgerald T, McCollom K, Moller R
Acta Pharmacol Toxicol (Copenh). 1983 Aug;53(2):146-52. doi: 10.1111/j.1600-0773.1983.tb01883.x.
To compare the antiarrhythmic activities of tocainide and lidocaine in dogs, a protocol was designed where the drug plasma levels were increased stepwise. This was achieved by computerizing bolus doses and infusion rates, using pharmacokinetic equations with constants, derived from previous experiments in similar animals. In conscious coronary-ligated dogs with ischaemic arrhythmias both compounds were active, causing a 50% reduction in VPB's at plasma concentrations of 5.0 micrograms/ml (tocainide) and 3.5 micrograms/ml (lidocaine). "Clearing" of catecholamine-induced arrhythmias was not obtained in any of six dogs given tocainide and only in two out of six dogs given lidocaine.
为比较妥卡尼和利多卡因对犬的抗心律失常活性,设计了一个方案,使药物血浆水平逐步升高。这是通过将大剂量推注和输注速率计算机化来实现的,使用的药代动力学方程中的常数来自之前在类似动物身上进行的实验。在有意识的冠状动脉结扎且患有缺血性心律失常的犬中,两种化合物均有活性,在血浆浓度为5.0微克/毫升(妥卡尼)和3.5微克/毫升(利多卡因)时,室性早搏减少50%。给予妥卡尼的6只犬中,没有一只能“消除”儿茶酚胺诱发的心律失常,而给予利多卡因的6只犬中只有2只可以。