Clevidipine in adult cardiac surgical patients: a dose-finding study.

Published

Journal Article

BACKGROUND: Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. METHODS: Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration-response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. RESULTS: There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 microg. kg-1. min-1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 microg/l and for a 20% or greater decrease in mean arterial pressure was 26.3 microg/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. CONCLUSION: Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.

Full Text

Duke Authors

Cited Authors

  • Bailey, JM; Lu, W; Levy, JH; Ramsay, JG; Shore-Lesserson, L; Prielipp, RC; Brister, NW; Roach, GW; Jolin-Mellgard, A; Nordlander, M

Published Date

  • May 2002

Published In

Volume / Issue

  • 96 / 5

Start / End Page

  • 1086 - 1094

PubMed ID

  • 11981147

Pubmed Central ID

  • 11981147

International Standard Serial Number (ISSN)

  • 0003-3022

Digital Object Identifier (DOI)

  • 10.1097/00000542-200205000-00010

Language

  • eng

Conference Location

  • United States