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


CONCLUSIONS
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.
Bailey
James M
JM
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. james_bailey@emory.org
Lu
Wei
W
Levy
Jerrold H
JH
Ramsay
James G
JG
Shore-Lesserson
Linda
L
Prielipp
Richard C
RC
Brister
Neil W
NW
Roach
Gary W
GW
Jolin-Mellgard
Ase
A
Nordlander
Margareta
M
D000465:Algorithms; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D011725:Pyridines; C118563:clevidipine