Pharmacokinetics and hemodynamics of amrinone in patients with chronic cardiac failure of diverse etiology.

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.