The effect of amiodarone pretreatment on survival of mice with cocaine toxicity.
BACKGROUND
Cocaine is a common drug of abuse and use has been associated with ventricular dysrhythmias. Published guidelines suggest that amiodarone is the first line antidysrhythmic for ventricular tachycardia and fibrillation. However, the effects amiodarone in the setting of cocaine toxicity are unknown and unstudied. The purpose of this study was to evaluate the safety and efficacy of amiodarone pretreatment in a murine model of acute cocaine toxicity.


METHODS
This was a randomized, blinded, placebo controlled investigation using male CF-1 mice weighing 29-37 g. First, the safety of an intraperitoneal dose of amiodarone (40 mg/kg) was confirmed in 5 mice. Second, based on preliminary investigations, an approximate intraperitoneal LD50 dose of cocaine (110 mg/kg) was identified and used as the cocaine dose in this study. Animals were then randomized to 2 groups. The control group received 0.5 mL of intraperitoneal 0.9% saline 30 minutes before cocaine. The study group received 40 mg/kg of intraperitoneal amiodarone (40 mg/kg) 30 minutes before cocaine. A blinded observer monitored mice for 2 hours after cocaine administration.


RESULTS
No mice in the amiodarone-only group developed any signs of toxicity or died. In the saline + cocaine group 31/32 (96.9%; 95% CI 83.8 to 99.9) mice seized with a median time to seizure of 2.5 minutes, and 23/32 (71.9%; 95% CI 52.3 to 86.3) died with a median time to death of 5.5 minutes. In the amiodarone + cocaine group 31/33 (93.9%; 95% CI 79.0 to 99.3) mice seized with a median time to seizure of 2.0 minutes, and 24/33 (72.7%; 95% CI 54.5 to 86.7) died with a median time to death of 6.0 minutes. All animals that died did so within 9 minutes. The difference in the proportion of animals dying in the amiodarone + cocaine group compared to the saline + cocaine group was 0.008 (-21 to 22%).


CONCLUSIONS
In this study, pretreatment with amiodarone in cocaine poisoned mice resulted in no change in seizure incidenceor mortality. However, definite conclusions about the reason for these findings cannot be drawn from this model.
DeWitt
Christopher R
CR
Medical Toxicology Fellow, Rocky Mountain Poison and Drug Center and Denver Health Medical Center, Denver, CO.
Cleveland
Nathan
N
Dart
Richard C
RC
Heard
Kennon
K
D000638:Amiodarone / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003042:Cocaine / Q000633:toxicity*; D004195:Disease Models, Animal; D004336:Drug Antagonism; D007274:Injections, Intraperitoneal; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011041:Poisoning / Q000517:prevention & control*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D019966:Substance-Related Disorders / Q000503:physiopathology / Q000517:prevention & control*; D014662:Vasoconstrictor Agents / Q000633:toxicity*
D000889:Anti-Arrhythmia Agents; D014662:Vasoconstrictor Agents; D003042:Cocaine; D000638:Amiodarone