Population pharmacokinetics of olprinone in patients undergoing cardiac surgery with cardiopulmonary bypass

Purpose Olprinone, a phosphodiesterase type III inhibitor, is a strong inotrope and vasodilator that does not increase oxygen consumption and is often used during weaning from cardiopulmonary bypass (CPB). To control the pharmacological effects of olprinone, pharmacokinetic information is essential; however, there is little published information on the pharmacokinetics of olprinone in a large population. Therefore, the purpose of this study was to determine olprinone pharmacokinetic parameters in a large population undergoing cardiac surgery with CPB. Methods Olprinone was infused at a rate of 0.2 µg/kg/min when weaning from CPB was started. Whole blood samples were periodically obtained to determine the olprinone concentrations using high-performance liquid chromatography. Measured olprinone concentrations were analyzed with a one-compartment model via a population approach. Results A total of 86 blood samples from 26 patients were used for pharmacokinetic analysis. The calculated clearance, volume of distribution ([V.sub.d]), and elimination half-life were 378 ml/min, 40.7 l, and 97.1 min, respectively. Olprinone clearance depended on weight and creatinine clearance, whereas [V.sub.d] depended only on weight. Conclusion We investigated the pharmacokinetic parameters of olprinone in patients undergoing cardiac surgery with CPB. Olprinone clearance depended on weight and creatinine clearance, whereas [V.sub.d] depended only on weight. When olprinone is infused according to the recommended dosing regimen, it takes more than 60 min to reach the target concentration (20 ng/ml). However, there is a possibility that a lower concentration is sufficient for weaning from CPB in combination with a continuous infusion of dopamine. Keywords Olprinone * Cardiac surgery * Cardiopulmonary bypass * Population pharmacokinetics
Introduction Phosphodiesterase type III inhibitors (PDEIs) have strong inotropic and vasodilatory effects [1-3] without increasing oxygen consumption in cardiomyocytes [4, 5]. They are also effective when there is downregulation of [...]