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.
RCT Entities:
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: Linnea R Burk; Jeffrey M Armstrong; H Hill Goldsmith; Marjorie H Klein; Timothy J Strauman; Phillip Costanzo; Marilyn J Essex Journal: Psychol Addict Behav Date: 2011-03
Authors: C M Oneta; U A Simanowski; M Martinez; A Allali-Hassani; X Parés; N Homann; C Conradt; R Waldherr; W Fiehn; C Coutelle; H K Seitz Journal: Gut Date: 1998-11 Impact factor: 23.059
Authors: Alexander Diehl; Bernhard Croissant; Anil Batra; Götz Mundle; Helmut Nakovics; Karl Mann Journal: Eur Arch Psychiatry Clin Neurosci Date: 2007-07-14 Impact factor: 5.270