Evaluation of the Effectiveness of Sugammadex for Digoxin Intoxication: An Experimental Study

Cardiovasc Toxicol. 2018 Oct;18(5):400-406. doi: 10.1007/s12012-018-9450-6.

Abstract

Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex. Heart rate, electrocardiography, and respiratory rate were monitored. The primary endpoint was time to asystole. Digoxin infusion continued until the animals arrested. The time to asystole for the Sgdx1000 group was significantly longer compared to that for the control group (p < 0.05). The mean lethal dose of digoxin was 5.35 ± 2.06 mg/kg in the saline-treated rats. On the other hand, the mean lethal dose of digoxin was 8.54 ± 1.51 mg/kg in the sugammadex 1000 group (p < 0.05). The mean lethal dose of digoxin was significantly higher than control group (p < 0.05). We found that the 1000 mg/kg dose of sugammadex delayed digoxin cardiotoxicity in a rat model of digoxin toxicity. We conclude that further research must be conducted on the interaction between digoxin and sugammadex.

Keywords: Cyclodextrin; Digoxin; Sugammadex; Toxicity.

MeSH terms

  • Animals
  • Antidotes / administration & dosage
  • Antidotes / pharmacology*
  • Cardiotoxicity
  • Digoxin / toxicity*
  • Heart Arrest / chemically induced
  • Heart Arrest / physiopathology
  • Heart Arrest / prevention & control*
  • Heart Rate / drug effects
  • Infusions, Intravenous
  • Injections, Intravenous
  • Myocardial Contraction / drug effects
  • Rats, Wistar
  • Sugammadex / administration & dosage
  • Sugammadex / pharmacology*
  • Time Factors

Substances

  • Antidotes
  • Sugammadex
  • Digoxin