Wilson H, Rocci M L, Weber K T, Andrews V, Likoff M J
Res Commun Chem Pathol Pharmacol. 1987 Apr;56(1):3-19.
The pharmacokinetics of amrinone and its relationship to ventricular function were assessed in 15 patients with chronic cardiac failure following the administration of a single 100 mg oral dose. Patients examined had Class II (1 patient), Class III (13 patients) and Class IV (1 patient) heart failure as characterized by the New York Heart Association classification. Blood samples were obtained following amrinone administration at selected times for 8 hours following the dose. Cardiac output was assessed serially for 5 hours following amrinone dosing. Mean (SD) peak plasma concentrations of amrinone (2.1 (1.1) mcg/ml) were obtained 0.5 to 2 hours after drug administration. The mean (SD) apparent oral clearance, apparent volume of distribution at steady state and half-life of amrinone were 0.23 (0.13) L/hr/kg, 1.2 (0.4) L/kg, and 4.8 (3.0) hr. Peak increases in cardiac index averaged 50% of baseline values and improvement was maintained at least 5 hours following amrinone dosing when compared to baseline cardiac index (p less than 0.05). Examination of the relationship between cardiac index corrected for baseline and amrinone plasma concentrations within individuals yielded strong and highly significant relationships (r greater than 0.90; p less than 0.025) in five patients, while in the remaining patients, either no relationship existed or insufficient data was available for analysis. When the data from all patients were pooled, a modest though significant relationship (r = 0.67; p less than 0.01) existed between cardiac index corrected for baseline and the post-absorptive, post-distributive amrinone plasma concentration. No difference in response to amrinone as a function of failure etiology or functional aerobic capacity was evident. Evaluation of the relationships between the mean improvement in cardiac index versus amrinone plasma concentration, as well as the time courses of these parameters indicate that the site of action of amrinone may be pharmacokinetically distinguishable from plasma and the tissues in instantaneous equilibrium with plasma.
在15例慢性心力衰竭患者单次口服100mg氨力农后，评估了氨力农的药代动力学及其与心室功能的关系。根据纽约心脏协会的分类标准，接受检查的患者中，有Ⅱ级（1例）、Ⅲ级（13例）和Ⅳ级（1例）心力衰竭患者。在给药后选定的时间点采集血样，持续8小时。在氨力农给药后连续5小时评估心输出量。给药后0.5至2小时测得氨力农的平均（标准差）血浆峰浓度为2.1（1.1）μg/ml。氨力农的平均（标准差）表观口服清除率、稳态分布容积和半衰期分别为0.23（0.13）L/（hr·kg）、1.2（0.4）L/kg和4.8（3.0）小时。心指数的峰值增加平均为基线值的50%，与基线心指数相比，氨力农给药后改善至少维持5小时（p<0.05）。在个体中，校正基线后的心指数与氨力农血浆浓度之间的关系检查显示，5例患者存在强且高度显著的关系（r>0.90；p<0.025），而其余患者要么不存在关系，要么没有足够的数据进行分析。当汇总所有患者的数据时，校正基线后的心指数与吸收后、分布后氨力农血浆浓度之间存在适度但显著的关系（r = 0.67；p<0.01）。未发现氨力农反应因衰竭病因或功能性有氧能力而有差异。对心指数平均改善与氨力农血浆浓度之间的关系以及这些参数的时间过程进行评估表明，氨力农的作用部位在药代动力学上可能与血浆以及与血浆处于瞬时平衡的组织不同。
