An in vitro study on the metabolic interaction between ethanol and caffeine at high concentrations using human liver microsomes

摘要

Caffeine (1,3,7-trimethylxanthine, CA) is a compound usually contained in beverages such as coffee and tea. CA is known to pharmacologically antagonize ethanol. Thus, the simultaneous intake of CA and ethanol takes place very commonly. Sometimes, toxic interactions also occur following combined intake of these two compounds. In this study, we conducted in vitro experiments to examine the interaction between ethanol and CA at high concentrations by observing mixed-function oxidation reaction using human liver microsomes. After incubation of the mixtures, CA and its three main metabolites theobromine (3,7-dimethylxanthine, TB), paraxanthine (1,7-dimethylxanthine, PX), and theophylline (1,3-dimethylxanthine, TP) were measured by high-performance liquid chromatography with ultraviolet detection. As results, the production of PX, the main metabolite of CA, was consistently inhibited by 24%–53% (P < 0.05) by high ethanol concentrations (20, 40, and 60 mM), but that of TP or TB was not. These results suggest that pharmacological or toxicological effects of CA may be enhanced by simultaneous use of ethanol and CA in humans.