Relationship between amrinone plasma concentration and cardiac index

Abstract

[Amrinone (5-amino-3,4''-bipyridine-6(1H)-one; Inocor) is a new potent inotropic drug.] Amrinone was given to 14 patients with congestive heart failure as an i.v. bolus (1 mg/s) at doses ranging from 0.5-3.5 mg/kg. Simultaneous determinations of cardiac index were made by thermodilution and of amrinone plasma concentration by high-performance liquid chromatography. A relationship between improvement in cardiac index and increasing plasma concentrations of amrinone was demonstrated for 13 of the 14 patients. The percentage increase in cardiac index correlated with amrinone plasma concentration (r = 0.81; P < 0.001). Amrinone was given to 4 patients as an i.v. bolus dose of 1.5 mg/kg followed by a constant infusion of 10 .mu.g/kg per min for 10 h; simultaneous determinations of cardiac index and circulating levels of amrinone indicated that both declined after the initial rise. The plasma concentration of amrinone remained relatively constant during the infusion at .apprx. 1.7 .mu.g/ml. In all cases, despite the relatively constant plasma levels there was a decline in cardiac index after .apprx. 4-5 h of infusion, but the cardiac index remained above the baseline; during the constant infusion, but the cardiac index remained above the baseline; during the constant infusion the cardiac index rose again and was maintained at a reasonably constant level for the last 3 h. Seven patients received oral doses of amrinone of .apprx. 3 mg/kg and simultaneous determinations of cardiac index and plasma concentration showed a relationship between amrinone level and rise in cardiac index (P < 0.05). In 16 patients after amrinone orally sufficient blood samples were taken to estimate the apparent 1st-order terminal elimination t1/2 [half-life]. The t1/2 as estimated by log-linear regression ranged from .apprx. 3-15 h; .hivin.x [mean] .+-. SEM [SE of mean] value was 8.3 (.+-. 1.1) h.