Circulatory Effects and Pharmacology of Clevidipine, a Novel Ultra Short Acting and Vascular Selective Calcium Antagonist, in Hypertensive Humans

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Abstract
The pharmacokinetics of clevidipine, a potent short-acting vascular-selective calcium antagonist, was investigated during steady state and the postinfusion period in patients with mild to moderate hypertension. Furthermore, the dose-effect and blood concentration-effect relations and the tolerability of the drug were studied. Twenty patients were randomized to clevidipine intravenously at target dose rates of 0.18, 0.91, 2.74, and 5.48 μg/kg/min, respectively, or placebo. Each patient received in random order three infusion rates of clevidipine or placebo during three separate study days. Dose-dependent reduction in blood pressure and a modest increase in heart rate were noted. The extremely high clearance value and the small volume of distribution resulted in short half-lives of clevidipine, 2.2 and 16.8 min, respectively. The blood concentration and dose rate producing half the maximal effect (i.e. EC50 and ED50) were ∼25 nM and 1.5 μg/kg/min, respectively. There was a linear relation between blood concentration and dose rate in the range studied. Clevidipine was safe and generally well tolerated; one patient was excluded because of adverse events at 2.74 μg/kg/min. In conclusion, clevidipine is a high-clearance calcium antagonist that may become a valuable contribution to the drugs used in conditions in which precise and rapid control of blood pressure is needed.

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