Abnormal quinidine binding in survivors of prehospital cardiac arrest

Abstract

Quinidine binding was studied in 15 survivors of prehospital cardiac arrest and was compared to 18 normal individuals and 20 patients with coronary artery disease. The unbound quinidine fraction was 6.3 ± 2.8% in the survivors of prehospital cardiac arrest, a value significantly lower than normal individuals (unbound quinidine fraction = 9.9 ± 3.0%, p < 0.005). Furthermore, unbound quinidine fraction correlated with interdose quinidine half-life in the six survivors of prehospital cardiac arrest where this could be measured ( r = 0.79, p < 0.05). The resultant quinidine interdose half-life was significantly prolonged (10 ± 3 hours) when compared to normal (6 ± 2 hours, p < 0.02). The reduction in free drug fraction in cardiac arrest survivors was a nonspecific finding in that free drug fraction was also reduced in the patients with coronary artery disease (unbound quinidine fraction = 7.4 ± 3%) and was independent of the α-1-glycoprotein concentration. Therefore survivors of prehospital cardiac arrest have a mean 40% reduction in free quinidine drug fraction which results in less free drug at any given total drug concentration and may relate to quinidine pharmacokinetics and pharmacodynamics in this patient group.