Ethanol As A Drug

Ethanol differs from most other drugs in the way it is absorbed into the blood, metabolized in the liver, and how it enters the brain and produces its pharmacological effect. Ethanol (CH3CH2OH) has a molecular weight of 46.05, mixes with water in all proportions and carries only a weak charge; this means that the molecules of ethanol easily pass through biological membranes, including the blood-brain barrier. After absorption into the portal blood, ethanol passes through the liver, where enzymes begin the conversion into acetaldehyde and acetate. The end products of ethanol metabolism are carbon dioxide and water. The concentrations of ethanol in biological specimens depend on the dose ingested, the time after drinking, and the water content of the materials analyzed. The concentration-time profiles of ethanol and the pharma-cokinetic parameters will differ depending on whether plasma, serum, urine, or saliva are the specimens analyzed. Several detailed reviews of ethanol pharmacokinetics are available and included in the bibliography.

Information about the absorption kinetics of ethanol is much less extensive than that about elimination kinetics. Unlike most other drugs, the dose of ethanol is not swallowed instantaneously because the drinking is usually spread over a period of time. For research purposes, however, ingestion of a bolus dose usually infers drinking times of five to fifteen minutes. The dosage form of ethanol, whether ingested as beer (3-6% w/v), wine (9— 12% w/v), spirits (32—40% w/v), or as a cocktail (15—25% w/v) might influence the pharmacokinetic parameters. Absorption of ethanol starts in the stomach where about 20 percent of the dose can become absorbed. The remainder is absorbed from the upper part of the small intestine. The speed of absorption of alcohol depends to a large extent on the rate of gastric emptying, which varies widely among different subjects. Assuming that the rate of absorption from the gut is a first-order process, one can represent the entire concentration-time profile of ethanol with a single equation:

Where C = BAC at some time t after administration

Co = Initial BAC extrapolated BAC (see Figure 2) k = First-order absorption rate constant ko = Zero-order elimination rate constant t = Time after drinking

The peak BAC and the time of reaching the peak after drinking are important aspects of the absorption kinetics. Table 1 gives examples of these parameters after healthy men drank neat whiskey (40% v/v or 80 proof) on an empty stomach. The absorption of ethanol occurs more slowly from the stomach than from the intestine owing to the enormous difference in the absorption surface available. Factors that influence gastric emptying, such as food in the stomach before drinking, will alter the rate of absorption and the peak BAC reached. The absorption of ethanol occurs progressively during a drinking binge or spree, and studies have shown that the BAC fifteen minutes after the last drink has reached about 80 percent of the final peak BAC. Because of the saturation-type kinetics, the peak BAC and the area under the curve (AUC) increase more than expected from proportional increases in the dose. The slower the rate of delivery of ethanol to the liver the smaller the AUC for a given dose and vice versa. The systemic availability (bioavailability) of drugs like ethanol with dose-dependent kinetics should not be calculated from the ratio of AUC after oral and intravenous administration.

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