Pharmacokinetics of amrinone during cardiac surgery

Amrinone is a nonglycosidic noncatecholamine with both vasodilator and positive inotropic effects that may be administered to patients undergoing cardiac surgery. As an initial step toward elucidating the optimal dosage of amrinone for cardiac surgical patients we studied the pharmacokinetics of amrinone during and after cardiac surgery requiring cardiopulmonary bypass. The study population comprised 35 adult patients, each receiving a single dose of amrinone (0.75, 1.5, 2.0, or 2.5 mg/kg) administered into the venous reservoir near the end of cardiopulmonary bypass. Additionally, 15 of the 35 patients also received intravenous infusions of either 5 or 10 micrograms.kg-1.min-1. Arterial blood was sampled over the next 22 h, and plasma concentrations of amrinone were determined by high-performance liquid chromatography. Protein binding of amrinone, assayed by equilibrium dialysis, was 21.6 +/- 2.5%. The decay of amrinone concentrations in plasma over time was fit to a biexponential equation by nonlinear least-squares regression. The manufacturer's recommended dose of 0.75 mg/kg followed by an infusion of 10 micrograms.kg-1.min-1 was inadequate to maintain the plasma concentration within the therapeutic range based on the pharmacodynamics of amrinone in patients with chronic congestive heart failure. This was due to significant redistribution of amrinone in the body after the loading dose. To maintain a therapeutic plasma concentration of 1.5-2.0 micrograms/ml, a larger loading dose or a supplemental loading dose as well as a continuous infusion is required.