Ethanol pharmacokinetics/kinetics

Alcohol dehydrogenase is a cytoplasmic enzyme mainly found in the liver, but also in the stomach. The enzyme accomplishes the first step of ethanol metabolism, oxidation to acetaldehyde, which is further metabolized by aldehyde dehydrogenase. Quantitatively, the oxidation of ethanol is more or less independent of the blood concentration and constant with time, i.e. it follows zero-order kinetics (pharmacokinetics). On average, a 70-kg person oxidizes about 10 ml of ethanol per hour. 

Non-linear pharmacokinetics are much less common than linear kinetics. They occur when drug concentrations are sufficiently high to saturate the ability of the liver enzymes to metabolise the drug. This occurs with ethanol, therapeutic concentrations of phenytoin and salicylates, or when high doses of barbiturates are used for cerebral protection. The kinetics of conventional doses of thiopentone are linear. With non-linear pharmacokinetics, the amount of drug eliminated per unit time is constant rather than a constant fraction of the amount in the body, as is the case for the linear situation. Non-linear kinetics are also referred to as zero order or saturation kinetics. The rate of drug decline is governed by the Michaelis-Menton equation ... 

The concept of clearance is useful in pharmacokinetics because clearance is usually constant over a wide range of concentrations, provided that ehmination processes are not saturated. Saturation of biotransformation and excretory processes may occur in overdose and toxic okinetic effects should be considered. If a constant fraction of drug is eliminated per unit time, the elimination follows first-order kinetics. However, if a constant amount of drug is eliminated per unit time, the elimination is described by zero-order kinetics. Some drugs, for example, ethanol, exhibit zero-order kinetics at normal or non-intoxicating concentrations. However, for any drug that exhibits first-order kinetics at therapeutic or nontoxic concentrations, once the mechanisms for elimination become saturated, the kinetics become zero order and clearance becomes variable.3... 

Drug information resources will not provide data on the elimination half-life of ethanol because, in the case of this drug, it is not constant. The elimination of ethanol follows zero-order kinetics because the drug is metabolized at a constant rate irrespective of its concentration in the blood (see Chapter 3). The pharmacokinetic relationship between elimination half-life, volume of distribution, and clearance, given by... 

D. Pharmacokinetics. Ethanol is readily absorbed (peak 30-120 min) and distributed into the body water (volume of distribution 0.5-0.7 L/kg or about 50 liters in the average adult). Elimination is mainly by oxidation in the liver and follows zero-order kinetics. The average adult can metabolize about 7-10 g of alcohol per hour, or about 12-25 mg/dL/h (this rate is highly variable depending on the individual). 

B. Pharmacokinetics. Methanol is readily absorbed and quickly distributed to the body water (Vd = 0.6 L/kg). It is not protein bound. It is metabolized slowly by alcohol dehydrogenase via zero-order kinetics, at a rate about one-tenth that of ethanol. The reported half-life ranges from 2 to 24 hours, depending on whether metabolism is blocked (eg, by ethanol or fomepizole). Only about 3% is excreted unchanged by the kidneys and less than 10-20% through the breath. 

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