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British Journal of Anaesthesia, 2000, Vol. 85, No. 5 683-689
© 2000 The Board of Management and Trustees of the British Journal of Anaesthesia

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

A. Vuylsteke1,*, Q. Milner1, H. Ericsson2, D. Mur1, J. Dunning1, Å. Jolin-Mellgård2, M. Nordlander2 and R. Latimer1

1Department of Anaesthesia, Papworth Hospital, Cambridge CB3 8RE, UK. 2AstraZeneca R&D Mölndal, Sweden

{dagger}This study was presented in part at the Thirteenth Annual Meeting of the European Association of Cardiothoracic Anaesthesiologists, Bergen, Norway, June 1998.

Clevidipine is a new vascular-selective, calcium channel antagonist of the dihydropyridine type with an ester side chain susceptible to esterase metabolism. In healthy volunteers, it has high clearance (0.069 litres min–1 kg–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 approximately 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 pharmacokinetics and the pulmonary extraction ratio of clevidipine in patients undergoing cardiac surgery. Seventeen patients received clevidipine as an i.v. infusion before cardiopulmonary bypass (CPB), and eight of these patients were also given clevidipine during hypothermic CPB. Mixed venous and arterial blood samples were taken for pharmacokinetic analysis and calculation of pulmonary extraction ratio. A two-compartment pharmacokinetic model with zero-order input was used to describe the pharmacokinetics of clevidipine before and during CPB. Virtually identical concentrations in mixed venous and arterial blood suggest negligible pulmonary metabolism of clevidipine. The total blood clearance of clevidipine is extremely high (0.055 litres min–1 kg–1). During CPB, clearance of clevidipine was significantly reduced, to 0.03 litres min–1 kg–1 (P<0.005), probably as a consequence of reduced body temperature.

Br J Anaesth 2000; 85: 683–9

* Corresponding author


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