Relationship between amrinone plasma concentration and cardiac index

Abstract

Amrinone was given to 14 patients with congestive heart failure as an intravenous bolus (1 mg/sec) at doses ranging from 0.5 to 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 less than 0.001). Amrinone was given to four patients as an intravenous bolus dose of 1.5 mg/kg followed by a constant infusion of 10 micrograms/kg/min for 10 hr; 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 about 1.7 micrograms/ml. In all cases, despite the relatively constant plasma levels there was a decline in cardiac index after about 4 to 5 hr of infusion, although 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 hr. Seven patients received oral doses of amrinone of about 3 mg/kg, and simultaneous determinations of cardiac index and plasma concentration showed a relationship between amrinone level and rise in cardiac index (p less than 0.05). In 16 patients after amrinone orally sufficient blood samples were taken to estimate the apparent first-order terminal elimination t 1/2. The t 1/2 as estimated by log-linear regression ranged from about 3 to 15 hr; mean +/- SEM value was 8.3 (+/- 1.1) hr.

Effects of cardiovascular disease on pharmacokinetics

“…Similar results were obtained by Wilson et al [77] and Rocci et al [78]. An even longer half-life (8.3 hours) after oral amrinone (150-300 mg) was found in patients with severe, chronic congestive HF (NYHA class III and IV; cardiac index, < 2.5 1/min/m 2) [79]. An even longer half-life (8.3 hours) after oral amrinone (150-300 mg) was found in patients with severe, chronic congestive HF (NYHA class III and IV; cardiac index, < 2.5 1/min/m 2) [79].…”

“…No significant differences in the kinetic parameters were noted between single and repeated doses (steady state) [78]. The kinetic modifications observed in these patients are probably related to the decreased blood flow to the kidney and the liver that is associated with congestive HF [79]. The kinetic modifications observed in these patients are probably related to the decreased blood flow to the kidney and the liver that is associated with congestive HF [79].…”

Effects of Inotropic Drugs on Mechanical Function and Oxygen Balance in Postischemic Canine Myocardium: Comparison of Dobutamine, Epinephrine, Amrinone, and Calcium Chloride

“…The range of epinephrine had been demonstrated in pilot studies to cause an increase of %SS comparable with that observed during dobutamine infusion. The blood concentrations for each inotropic agent examined include the clinical dose range (dobutamine, 0.1-0.2 µg/mL; amrinone 2-7 µg/mL) (14, 15). Each inotropic drug was infused for 3 to 5 min in incremental doses administered 8 to 10 min apart each.…”

Pharmacokinetics of Cardiovascular Drugs in Children

“…Edelson et al [139] measured plasma concentrations of amrinone in adult patients with congestive heart failure following an intravenous bolus injection of 0.5 to 3.5 mg/kg of body weight, with simultaneous measurement of cardiac index. A direct linear correlation between the percentage increase in cardiac index and amrinone plasma concentration was demonstrated over a range of 0.5 to 7 mg/L, with a 50% increase in cardiac index corresponding to a plasma concentration of 3.7 mglL.…”