Evaluation of the Effectiveness of Sugammadex for Verapamil Intoxication

Abstract

Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with verapamil at 37.5mg/kg/h. Five minutes after the start of infusion, the animals were treated with a bolus of either 16mg/kg, 100mg/kg or 1000mg/kg sugammadex. The control group was treated with an infusion without sugammadex. The heart rate and respiratory rate were monitored, and an electrocardiogram was recorded. The primary end-point was the time to asystole. The verapamil infusion continued until the animals arrested. The asystole time for the S16 group was significantly longer compared to those for the control and S1000 groups (p<0.05). The asystole time for the S1000 group was significantly shorter than those for all of the other groups (p<0.05). Reflecting these data, there was a near doubling of the mean lethal dose of verapamil from 13.57mg/kg (S.D. ±8.1) in the saline-treated rats to 22.42mg/kg (S.D. ±9.9) in the sugammadex 16 group (p<0.05). However, for the sugammadex 1000 group, the mean lethal dose was found to be 6.28±1.11mg/kg. This dose is significantly lower than those for all of the other groups (p<0.05). We found that treatment with 16mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.