Developmental changes in alcohol pharmacokinetics in rats.

Developmental changes in the pharmacokinetics of alcohol could influence the outcome of alcohol exposure during different periods of postnatal development. Hence, the development of the ability to absorb and metabolize alcohol in the rat was examined by administering an acute dose (2.5 g/kg) of ethanol in milk formula by intragastric intubation to rats of 1, 2, 4, 6, 8, 10, 15, 21, 30, and 60 days of age. Each animal in a particular litter was assigned a different time point following intubation when its blood alcohol concentration (BAC) was determined from a tail blood sample. At all ages tested, maximum BACs occurred between 1.25 and 1.5 hr following intubation. However, maximum BACs decreased with age from 155 mg/dl in 1-day-old rats to 111 mg/dl in 60-day-old rats. Furthermore, the rate of alcohol clearance was slower in the younger rats. By linear regression analysis, the elimination rate of alcohol in 1-day-old rats was estimated to be 7.5 mg/dl/hr which increased to 42.2 mg/dl/hr in 60-day-old-rats. By 8 hr following intubation, rats that were 21 days of age and older had completely cleared the alcohol, whereas the younger rats (1-15 days of age) had not. No consistent sex differences were seen in either the maximum BAC or clearance rate. Since developmental changes in the ability to clear alcohol occur throughout the first 60 postnatal days in the rat, controlling for these changes is essential when looking for critical periods of an organ's vulnerability to damage by alcohol.