Elimination Rates And Enzymes

Differences in the rate of disappearance of etha-nol from blood might depend on genetic and environmental factors influencing an individual s catalytic activity of alcohol-metabolizing enzymes. In humans, the enzyme ADH occurs in multiple molecular forms, designated class I, II, and III. Class I enzymes are located mainly in the liver cytosol and have a low km for ethanol. Various isozymes (variations within a class) exist and ^-ADH (class I) is predominant in Caucasians whereas ^2-ADH (class II) is the most abundant isozyme in Asians. The

Figure 2

Examples of Concentration-Time Profiles of Alcohol Taken by Intravenous and Oral Routes of Administration. Examples of concentration-time profiles of ethanol obtained after intravenous infusion of 0.4 g ethanol/ kg body weight in 15 minutes (upperpart) and after ingestion of 0.8 g/kg (lower part). Several key pharmacokinetic parameters are shown.

rate of ethanol elimination in the various racial groups is not much different from the variations seen within a single racial group in well-designed studies that allow for racial differences in body composition—the proportion of fat to lean body mass.

Alcoholics have a greater capacity to eliminate ethanol than do moderate drinkers. Disappearance rates from blood of 30 mg/dl/h are not uncommon—compared with a mean rate of only 15 mg/ dl/h (range 8-20 mg/dl/h) in moderate drinkers. The liver microsomes contain enzymes capable of oxidizing ethanol as well as other drugs, organic solvents, and environmental chemicals. One particular form of the cytochrome P450 enzyme (denoted P450IIEI) metabolizes ethanol. This microsomal ethanol oxidizing system (MEOS) has a km of 4060 mg/dl (8.7-13 mmol/l) compared with 2-5 mg/dl (0.4-1 mmol/l) for human ADH. More importantly, the P450IIEI isozyme becomes more active during prolonged exposure to ethanol—a process known as enzyme induction. Accordingly, because of continuous heavy drinking, alcoholics develop a high capacity for eliminating ethanol from the blood. Their enhanced capacity vanishes after a short period of abstinence, however, but liver disease (hepatitis, cirrhosis) in alcoholics does not seem to impair their ability to dispose of ethanol.

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