title: Disposition and first-pass metabolism of ethanol in humans: is it gastric or hepatic and does it depend on gender?
abstract: OBJECTIVE
  To assess the extent and site of the first-pass metabolism of ethanol and to examine whether first-pass metabolism and disposition of ethanol are dependent on gender.
  
  
  METHODS
  After a standardized lunch, healthy subjects (six women and six men) received on two separate occasions a 60-minute intravenous infusion of ethanol (0.3 gm/kg) and concomitantly an equimolar dose of d3-ethanol/kg either orally (over 20 minutes) or intraduodenally (infused over 30 minutes). Blood levels, urinary excretion of d0- and d3-ethanol, and sedative effects were monitored for 6 hours. Disposition and first-pass metabolism of ethanol were evaluated by applying an open two-compartment model with Michaelis-Menten elimination.
  
  
  RESULTS
  Comparison of the corresponding intravenous/oral versus intravenous/intraduodenal data of each individual revealed that total first-pass metabolism (gastric plus hepatic) was not pronounced in either males (9.1% +/- 4.0%; mean +/- SD) or females (8.4% +/- 3.1%) and that this first-pass metabolism was partly of gastric origin. Dose-corrected values for area under blood concentration-time curve were on average 28% higher (p < 0.0001) in the women than in the men. Mean total blood ethanol disappearance rate was higher (p < 0.001) in women (3.92 +/- 0.40 mmol/L . hr) than in men (3.19 +/- 0.48 mmol/L . hr). Renal clearance was gender-independent and negligible. A linear relationship (p < 0.001) could be found between the blood levels of ethanol and sedation index. Because the slope was steeper in women (1.04) than in men (0.42) a higher central nervous system sensitivity to the sedative effects of ethanol in women can be assumed.
  
  
  CONCLUSIONS
  Under realistic life conditions (social drinking of moderate doses of ethanol after a light lunch) only a minor, gender-independent first-pass metabolism is observed that is partly of gastric origin.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Ammon
authors.forename: C
authors.initials: C
authors.lastname: Schäfer
authors.forename: U
authors.initials: U
authors.lastname: Hofmann
authors.forename: U
authors.initials: U
authors.lastname: Klotz
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012727:Sex Characteristics; D014018:Tissue Distribution
chemical_list: D000431:Ethanol