title: Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats.
abstract: BACKGROUND
  A 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.
  
  
  METHODS
  Ethanol, 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.
  
  
  RESULTS
  Ethanol 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.
  
  
  CONCLUSIONS
  An 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.
authors.affiliation: Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland. Electronic address: eflorek@ump.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Florek
authors.affiliation: Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Maksymilian
authors.initials: M
authors.lastname: Kulza
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Jagiellonian University, Kraków, Poland; Laboratory of High Resolution Mass Spectrometry, Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Piekoszewski
authors.affiliation: Laboratory of Analytical Toxicology and Drug Monitoring, Jagiellonian University, Kraków, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Gomółka
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University, Kraków, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jawień
authors.affiliation: Department of Forensic Medicine, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Teżyk
authors.affiliation: Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Napierała
mesh_terms: D000079:Acetaldehyde / Q000097:blood; D000428:Alcohol Drinking / Q000523:psychology*; D000438:Alcohols / Q000097:blood; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000493:pharmacokinetics*; D003367:Cotinine / Q000097:blood; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D012906:Smoke / Q000009:adverse effects*
chemical_list: D000438:Alcohols; D002492:Central Nervous System Depressants; D012906:Smoke; D000431:Ethanol; D000079:Acetaldehyde; D003367:Cotinine
keywords: Alcohol preferring rats; Animals; Ethanol; Pharmacokinetic interactions; Tobacco smoke