Pharmacokinetics and pulmonary extraction of clevidipine, a new vasodilating ultrashort-acting dihydropyridine, during cardiopulmonary bypass

Clevidipine is a new vascular-selective, calcium channel antagonist of the dihydropyridine type with an ester side chain susceptible to esterase metab olism. In healthy volunteers, it has high clearance (0.069 litres min(-1) k g(-1)) with a small volume of distribution at steady state (0.19 litres kg( -1)). The half-lives of the two initial rapid phases, accounting for approx imately 95% of the area under the curve after an i.v. bolus, are 0.7 and 2. 3 min, respectively. The aims of this study were to determine the pharmacok inetics and the pulmonary extraction ratio of clevidipine in patients under going cardiac surgery. Seventeen patients received clevidipine as an i.v. i nfusion before cardiopulmonary bypass (CPB), and eight of these patients we re also given clevidipine during hypothermic CPB. Mixed venous and arterial blood samples were taken for pharmacokinetic analysis and calculation of p ulmonary extraction ratio. A two-compartment pharmacokinetic model with zer o-order input was used to describe the pharmacokinetics of clevidipine befo re and during CPB. Virtually identical concentrations in mixed venous and a rterial blood suggest negligible pulmonary metabolism of clevidipine. The t otal blood clearance of clevidipine is extremely high (0.055 litres min(-1) kg(-1)). During CPB, clearance of clevidipine was significantly reduced, t o 0.03 litres min(-1) kg(-1) (P<0.005), probably as a consequence of reduce d body temperature.