PHARMACOKINETICS OF INTRAVENOUS MILRINONE IN PATIENTS UNDERGOING CARDIAC-SURGERY

Background: Milrinone is a phosphodiesterase inhibitor with positive i notropic and vasodilator effects that are useful in the treatment of v entricular dysfunction after cardiac surgery. However, the pharmacokin etics of the drug have been investigated only in healthy volunteers an d in patients with chronic congestive heart failure. This study invest igates the pharmacokinetics of milrinone in adult cardiac surgical pat ients after cardiopulmonary bypass. Methods: Milrinone was administere d to 25 patients just before or immediately after separation from card iopulmonary bypass. Arterial blood was sampled over the next 16 h and milrinone plasma concentrations were determined by highperformance liq uid chromatography. Data mere analyzed by extended nonlinear least-squ ares regression. The relation between milrinone plasma concentration a nd hemodynamic effect was examined in an additional 11 patients who ha d cardiac indices less than 2.51.min(-1).m(-2) immediately after separ ation from cardiopulmonary bypass. Milrinone was administered and plas ma concentrations were related to changes in cardiac index during the next 10 min. Results: A milrinone dose of 50 mu g/kg in conjunction wi th an infusion of 0.5 mu g.kg(-1).min(-1) consistently maintained plas ma concentrations in excess of 100 ng/ml. A triexponential equation de scribing the plasma concentration as a function of time was used to de scribe the data. Central-compartment volume was 102 ml/kg, volume of d istribution was 1,638 ml/kg, and elimination clearance was 1.88 ml.kg( -1).min(-1). Pharmacokinetic parameters were independent of dose. The relation between plasma concentration and percentage increase in cardi ac index could be described by a sigmoidal curve with the plasma conce ntration associated with a 50% increase in cardiac index equal to 167 ng/ml. Conclusions: A milrinone dose of 50 mu g/kg with an infusion at 0.5 mu g.kg(-1)min(-1) maintains plasma concentrations at or above th e threshold of therapeutic effects.