Pharmacokinetics of verapamil in overdose

The information on the pharmacokinetics of verapamil in overdose is scanty. We report two adults who ingested 3.2 g and 4 g of verapamil, respectively. Both patients had hypotension and a severe bradycardia. The highest plasma verapamil concentration in these patients was about 2200 ng/ml and 2700 ng/ml, respectively. The decline in plasma verapamil and norverapamil concentrations followed first-order kinetics, and the half-life of verapamil was 7.8 h and 15.1 h, respectively. The free fraction of verapamil (non-protein bound) was higher at total concentrations exceeding 2000 ng/ml (12-15%) than at lower concentrations (2-6%). There seems to be no marked saturation of the metabolism of verapamil in acute poisoning. The apparent concentration-dependent changes in the free fraction may be due to therapeutic measures.