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Purpose Olprinone is a phosphodiesterase type III inhibitor that is often used to increase cardiac output after cardiopulmonary bypass (CPB). Hemodilution by CPB is likely to decrease total olprinone concentration, but it may also increase the free (unbound) concentration of olprinone due to reduced protein binding. The aim of this study was to investigate the effect of hemodilution on the protein binding of olprinone. Methods Eleven patients scheduled for elective cardiac surgery with CPB were enrolled in our study. Olprinone was continuously infused at a rate of 0.2 µg/kg/min from the time of the first surgical incision until the patient arrived at the recovery unit. Protein binding was evaluated twice, just before the start of CPB and at the beginning of withdrawal from CPB. Olprinone concentration and protein binding were determined with high-performance liquid chromatography and ultrafiltration methods, respectively. Olprinone protein binding was also evaluated in vitro. Results Olprinone protein binding to albumin was 63 % in vitro, but it did not bind to alpha-1 acid glycoprotein. Olprinone protein binding in patients before CPB was 81.5 ± 4.3 %, whereas protein binding at withdrawal from CPB was 63.3 ± 14.3 %. Conclusions Unbound olprinone concentration increased by 20 % during CPB, which suggests that the pharmacological effects of olprinone might be enhanced during and after CPB. Close hemodynamic monitoring is necessary to control the effects of olprinone after CPB, because CPB alters olprinone's pharmacokinetics. Keywords Olprinone * Cardiac surgery * Cardiopulmonary bypass * Protein binding * Albumin, Introduction Olprinone (Coretec®; Eisai, Tokyo, Japan) is a phosphodiesterase type III inhibitor (PDEI) with both strong inotropic and vasodilatory effects [1] that is often used in cardiac surgery for weaning [...]

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 [...]