title: Tolerance and pharmacokinetics of flunarizine after cardiac arrest. The Cerebral Resuscitation Study Group.
abstract: Neuronal calcium overloading after complete ischemia-anoxia of the brain might be the primary process initiating chemical cascades which lead to cell death. According to this hypothesis calcium-entry blocking agents act on the final common pathway of brain damage. Flunarizine, a selective calcium-entry blocker (without influence on heart rate and on cardiac contractile force), was administered to 12 unconscious patients, recovering from cardiac arrest (CA) of cardiac origin, according to a strict dose-range infusion protocol. Blood-pressure and heart rate (HR) were recorded before, during (t = 10 min, 20 min) and after (t = 30 min, 2 h, 4 h, 6 h, 8 h) each flunarizine infusion (maximum 4 infusions). A significant, although not clinically relevant, decrease in heart rate was noted during the first infusion. Systolic (SBP) and diastolic blood pressure (DBP) also decreased during the infusion without reaching statistical significance. Plasma levels of flunarizine were determined before and after each infusion (t = 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h). Flunarizine plasma concentrations declined very rapidly after cessation of each infusion. Sequential half-lives were in the order of 11-19 min and 5-7 h, and primarily reflect rates of distribution between the systemic circulation and the rapidly equilibrating tissues such as the brain. No substantial accumulation of flunarizine was described and plasma levels were proportional to the give dose. Therefore, flunarizine pharmacokinetics can be considered as linear for doses up to 50 mg.
authors.affiliation: Department of Intensive Care and Emergency Medicine, University Antwerp, UIA, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Van Hoeyweghen
authors.forename: E
authors.initials: E
authors.lastname: Vercammen
authors.forename: L
authors.initials: L
authors.lastname: Bossaert
mesh_terms: D002319:Cardiovascular System / Q000187:drug effects*; D005444:Flunarizine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006323:Heart Arrest / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009994:Osmolar Concentration
chemical_list: D005444:Flunarizine