Clinical pharmacokinetics of ethanol.
The pharmacokinetics of ethanol after typical doses are described by a 1-compartment model with concentration-dependent elimination. The volume of distribution estimated from blood concentrations is about 37 L/70 kg. Protein binding of ethanol has not been reported. Elimination is principally by metabolism in the liver with small amounts excreted in the breath (0.7%), urine (0.3%), and sweat (0.1%). Metabolism occurs, principally by alcohol dehydrogenase, in the liver to acetaldehyde. Models of ethanol input and absorption are crucial to the description and understanding of the effects of ethanol dose on bioavailability. Little attention has been paid to evaluation of potential models. First-pass extraction of ethanol is predicted to be dependent on hepatic blood flow and ethanol absorption rate, with a typical extraction ratio of 0.2. The overall elimination process can be described by a capacity-limited model similar to the Michaelis-Menten model for enzyme kinetics. The maximum rate of elimination of ethanol (elimination capacity or Vmax is 8.5 g/h/70 kg. This would be equivalent to a blood ethanol disappearance rate of 230 mg/L/h if metabolism took place at its maximum rate. The elimination rate is half of the elimination capacity at a peripheral blood ethanol concentration (Km) of about 80 mg/L. Ethanol is readily detectable in expired air. The usual blood:expired air ratio is 2300:1 and breath clearance at rest is 0.16 L/h. The renal clearance of ethanol is 0.06 L/h and sweat clearance is 0.02 L/h. The use of a zero-order model of ethanol elimination has been widespread although the limitations of this model have been known for a long time. Much of the published work on ethanol pharmacokinetics must be regarded with suspicion because of this assumption.
Holford
N H
NH
Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland.
D000426:Alcohol Dehydrogenase / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological
D000431:Ethanol; D000426:Alcohol Dehydrogenase