Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats

BackgroundA vast majority of people who abuse alcohol are also defined as “heavy smokers”. Tobacco smokes induces CYP1A1, CYP1A2, CYP2A6 isoenzymes, but on the other hand, ethanol activates CYP2E1, which can be important during combined, chronic use of both of them. The aim of the study was to evaluate the influence of tobacco smoke xenobiotics on ethanol pharmacokinetics and the level of its metabolites in alcohol preferring and non-preferring rats.MethodsEthanol, acetaldehyde, methanol, n-propanol and n-butanol were determined in whole blood by means of gas chromatography. Cotinine in serum was determined by LC–MS/MS. A non-compartmental analysis (cotinine, acetaldehyde) and Widmark equation (ethanol) were used for pharmacokinetic parameters calculation.ResultsEthanol levels were lower in animals exposed to tobacco smoke compared to rats receiving this xenobiotic, without a prior exposure to tobacco smoke. Lower values of the studied pharmacokinetic parameters were observed in the alcohol preferring males compared to the non-alcohol preferring rats. Both n-propanol and n-butanol had higher values of the pharmacokinetic parameters analyzed in the animals exposed to tobacco smoke and ethanol compared to those, which ethanol was administered only once.ConclusionsAn increase in maximum concentration and the area under concentration–time curve for ethanol after its administration to rats preferring alcohol and exposed to tobacco smoke are accompanied by a decrease in the volume of distribution. The changes in the volume of distribution may be caused by an increase in the first-pass effect, in the intestinal tract and/or in the liver. The acetaldehyde elimination rate constant was significantly higher in alcohol-preferring animals.