A Probabilistic Inference Framework for Nonlinear Compartmental Systems with Application to Blood Alcohol Dynamics

Rising blood alcohol concentration (BAC) may result from continued absorption following alcohol ingestion, ongoing alcohol consumption, or endogenous ethanol production by the gut microbiota (auto-brewery syndrome). Distinguishing these possibilities is a common clinical and forensic challenge, yet the duration over which a rising BAC remains compatible with alcohol ingestion alone has not been quantified. We developed a physiologically based probabilistic framework to estimate the expected timing of peak BAC under ingestion-only conditions. Ethanol pharmacokinetics were modeled using a compartmental model incorporating gastric emptying, intestinal absorption, systemic distribution, and Michaelis-Menten elimination. Inter-individual variability in physiological and behavioral parameters was incorporated using Monte Carlo simulation of 10,000 virtual individuals. Peak BAC timing was calculated from both the start and the cessation of drinking, with the latter representing the clinically relevant endpoint. The median time from cessation of drinking ) to peak BAC () was 81.1 minutes, with 95th and 99th percentiles of 103.4 and 111.0 minutes, respectively. In the baseline simulation, the maximum post-cessation peak time was 122.4 minutes. Sensitivity analyses identified ethanol dose and elimination capacity as the strongest determinants of delayed peak BAC, with the largest simulated post-cessation peak time reaching 149.6 minutes in the combined-parameter analysis. In the baseline simulation, 0.04% of peaks occurred more than 120 minutes after cessation, and none occurred after 135 or 150 minutes. In the most delayed combined scenario, the probabilities of peak BAC occurring more than 120, 135, and 150 minutes after cessation were 100%, 48.16%, and 0%, respectively. Rather than defining a fixed physiological cutoff, this study provides the first probabilistic framework for estimating whether a continued rise in BAC remains compatible with alcohol ingestion alone or warrants consideration of alternative explanations, including endogenous ethanol production in auto-brewery syndrome.