Abstract
Objective: To determine the pharmacokinetics and pharmacodynamics of clevidipine, a new ultrashort-acting calcium antagonist, in healthy male volunteers following a constant rate infusion.
Methods: Eight healthy male volunteers received 1030 nmol · min−1 of clevidipine together with a tracer dose of 3[H]-clevidipine for 1 h as an i.v. infusion. Frequent venous blood samples and effect recordings were obtained during ongoing infusion and up to 32 h following termination of the infusion. The excretion of radioactivity in urine and faeces was followed for 7 days.
Results: A two-compartment model gave the best fit to the individual clevidipine blood levels, resulting in a mean blood clearance of 0.14 (0.03) l · min−1 · kg−1 and a mean volume of distribution at steady state of 0.6 (0.1) l · kg−1. The initial half-life was 1.6 (0.3) min, and the terminal half-life was 15 (5) min. The maximum concentration of the metabolite H 152/81 was reached 2.2 (1.3) min following termination of the infusion. The mean terminal half-life of the inactive primary metabolite was 9.5 (0.8) h and the mean recovery of the radioactive dose reached 83 (3)%. Following termination of the 1 h infusion, the effect on blood pressure (BP) and heart rate was back to pre-dose values within 15 min.
Conclusion: Clevidipine is a high clearance drug, which is rapidly metabolized to the corresponding inactive acid. The tmax value of the primary metabolite, and a virtually identical value of the initial half-life and the half-life for elimination from the central compartment, indicate that the initial rapid decline of the post-infusion blood levels is mainly due to elimination rather than distribution. The duration of action of clevidipine is short.
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Received: 23 September 1998 / Accepted in revised form: 20 November 1998
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Ericsson, H., Fakt, C., Höglund, L. et al. Pharmacokinetics and pharmacodynamics of clevidipine in healthy volunteers after intravenous infusion. E J Clin Pharmacol 55, 61–67 (1999). https://doi.org/10.1007/s002280050594
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DOI: https://doi.org/10.1007/s002280050594