Role of variability in explaining ethanol pharmacokinetics: research and forensic applications.
Level 5 - mechanism / opinion, no new human data
Narrative review without systematic methodology or primary human experimental data
PubMed 12489977 · doi:10.2165/00003088-200342010-00001
What was done
Narrative review evaluating the genetic, physiological, environmental, and methodological sources of variability in ethanol absorption, distribution, metabolism, and elimination, and their implications for pharmacokinetic modeling in clinical and forensic contexts.
What was found
The bulk of ingested ethanol (95% to 98%) is metabolised, with the remainder excreted in breath, urine, and sweat. Alcohol dehydrogenase (ADH) has a low Michaelis-Menten constant (Km) of 0.05 to 0.1 g/L and quickly becomes saturated at moderate doses, producing zero-order elimination kinetics across much of the concentration-time course. Cytochrome P450 2E1 has a higher Km (0.5 to 0.8 g/L) and is inducible in heavy drinkers. Variability is further driven by fed versus fasted state, beverage concentration, body water differences across sex and age, tissue blood flow, and ADH polymorphisms. The review notes that multicompartment models describe ethanol disposition better than traditional one-compartment models.
Why it matters
Understanding the multi-factorial and non-linear drivers of ethanol disposition is critical for accurate clinical toxicity assessment and legal retrograde extrapolations of blood alcohol concentration.
Limits
As a narrative review, it lacks a systematic literature search, standardized inclusion criteria, or pooled statistical meta-analyses. The abstract does not provide specific sample sizes or quantitative bounds for between- and within-subject variance.
Cited by
- supports Over 90% of alcohol consumed is oxidized in the body, with the remaining 10% excreted in breath, sweat, and urine.