Cocaine metabolism in humans after use of alcohol. Clinical and research implications.

The simultaneous administration of cocaine and alcohol implies a pharmacological interaction at pharmacodynamic and pharmacokinetic levels. The latter involves an alteration of cocaine kinetics and metabolism, as well as the biosynthesis of newly active metabolites, such as cocaethylene. Cocaethylene is metabolized along the same pathways as cocaine. Its detection in biological samples indicates the combined consumption of cocaine and alcohol. From epidemiological and toxicological data, it has been suggested that the combination of alcohol and cocaine produces an increased toxicity in addition to behavioral changes. There has been some debate regarding the contribution of cocaethylene to this rise of toxicity. Its pharmacological and toxicological profile is very similar to cocaine. During the interaction of both substances, the rise in cocaine plasma concentrations can explain many of cardiovascular and behavioral effects observed. The contribution of cocaethylene to the interaction is probably minor; its effects are likely additive to those of cocaine. Perhaps its longer elimination half-life can help in understanding long-lasting effects of the alcohol-cocaine combination.