Effects of cocaine administration route on the formation of cocaethylene in drinkers: an experiment using rats

The effects of cocaine administration route on the formation of cocaethylene, an active metabolite of cocaine produced in the presence of ethanol, were investigated using rats. When 20 mg/kg cocaine was administered into the stomach together with 2 g/kg ethanol, maximum liver concentrations of cocaine and cocaethylene, 8410 +/- 3600 and 1680 +/- 520 ng/g, respectively, were observed at 15 min. In other tissues the maximum levels of both the substances were attained in 30 min, but were much lower than those in the liver. Intramuscular administration of 20 mg/kg cocaine with 2 g/kg oral ethanol gave levels of liver cocaine as low as 103 +/- 29 to 150 +/- 35 ng/g, resulting in no detection of liver cocaethylene over the entire 180-min study period, although gradual accumulation of cocaethylene was observed in other tissues. The accumulation patterns of cocaine and cocaethylene in blood of alcohol-intoxicated rats after the i.m. administration of cocaine were similar to those in blood of drinkers after nasal insufflation of cocaine. Despite i.v. administration of 1 mg/kg cocaine with 2 g/kg oral ethanol, no detectable amounts of cocaethylene appeared in any tissues over the entire 60-min study period. The present findings are considered to be of importance in the fields of forensic and clinical toxicology for clarifying (1) the rate of in vivo cocaethylene formation and (2) the distribution of cocaine and cocaethylene in blood and tissues.