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Wednesday, October 26, 2011

Biotransformation of ethanol to ethyl glucuronide in a rat model after a single high oral dosage



Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest that maximum blood EtG (BEtG) concentrations are reached between 3.5 and 5.5h after ethanol administration.

This study was undertaken to determine if the Sprague–Dawley (SD) rat biotransforms ethanol to EtG after a single high oral dose of ethanol.

SD rats (male, n=6) were gavaged with a single ethanol dose (4g/kg), and urine was collected for 3h in metabolic cages, followed by euthanization and collection of heart blood. Blood and urine were analyzed for ethanol and EtG by gas chromatography and enzyme immunoassay.

Blood and urine ethanol concentrations were 195±23 and 218±19mg/dL, whereas BEtG and urine EtG (UEtG) concentrations were 1,363±98ng equivalents/mL and 210±0.29mg equivalents/dL .

Sixty-six male SD rats were gavaged ethanol (4g/kg) and placed in metabolic cages to determine the extent and duration of ethanol to EtG biotransformation and urinary excretion. Blood and urine were collected up to 24h after administration for ethanol and EtG analysis.

Maximum blood ethanol, urine ethanol, and UEtG were reached within 4h, whereas maximum BEtG was reached 6h after administration. Maximum concentrations were blood ethanol, 213±20mg/dL; urine ethanol, 308±34mg/dL; BEtG, 2,683±145ng equivalents/mL; UEtG, 1.2±0.06mg equivalents/mL .

Areas under the concentration–time curve were blood ethanol, 1,578hmg/dL; urine ethanol, 3,096hmg/dL; BEtG, 18,284hng equivalents/mL; and UEtG, 850hmg equivalents/dL.

Blood ethanol and BEtG levels were reduced to below limits of detection (LODs) within 12 and 18h after ethanol administration. Urine ethanols were below LOD at 18h, but UEtG was still detectable at 24h after administration.

Our data prove that the SD rat biotransforms ethanol to EtG and excretes both in the urine and suggest that it is similar to that of the human.


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