Extended absorption, implications: Rethinking alcohol pharmacokinetics in forensic calculations

Abstract

Forensic toxicologists routinely perform pharmacokinetic calculations for alcohol, such as retrograde extrapolation calculations that rely on assumptions about when alcohol absorption is complete. However, examination of current practice reveals a uniformity in applying standardised timing assumptions despite well-documented individual variation in alcohol pharmacokinetics. This paper highlights factors that can influence alcohol absorption and cause the absorption of alcohol to extend beyond the conventional 2-hour timeframe since the last drink. Various physiological conditions, including the presence of food, certain medications, medical conditions and other factors, can prolong alcohol absorption beyond 2 hours. Toxicologists performing pharmacokinetic calculations for alcohol should disclose that population averages regarding the absorption of alcohol may not apply to individual cases.

Introduction

Consider this scenario: The driver of a car consumed alcohol with dinner, crashed it 2 hours later, and had blood drawn another hour afterward. A forensic toxicologist is asked to perform a retrograde extrapolation to estimate the alcohol concentration within 2 hours of driving (a standard timeframe used for prosecution in impaired driving cases). Many toxicologists will assume alcohol absorption was complete within 2 hours of the last drink and perform a retrograde extrapolation to estimate the subjects’ alcohol concentration at that time.

In order for a retrograde extrapolation calculation to be performed accurately, however, the subject must be in the post-absorptive phase of alcohol elimination. If the subject is still absorbing alcohol or is in a plateau phase, the calculation will overestimate the subject’s blood alcohol concentration (BAC).^1–3 Several factors can delay the absorption of alcohol beyond the commonly assumed 2-hour window of absorption. Consumption of a large meal, medications that slow gastric emptying, medical conditions affecting gastrointestinal motility, such as gastroparesis or gastroesophageal reflux disease (GERD) and blood loss due to trauma may extend absorption by several hours. These factors could alter the absorption timeline and subsequent accuracy of a retrograde extrapolation estimate. Yet, current forensic practice rarely accounts for such individual variations.

An analysis of retrograde extrapolation reports from the Minnesota Bureau of Criminal Apprehension (BCA) toxicology section was conducted. The reports were obtained from a government data practice request for retrograde extrapolation reports authored during 2023 and 2024. A total of 36 reports were provided and reviewed. Each report was evaluated for whether the absorption of alcohol was assumed to be ⩽2 hours. In addition, reports were reviewed for whether or not the following factors were taken into consideration as potential factors in delaying the absorption of alcohol beyond 2 hours: medications taken, medical conditions (such as gastroparesis or gastroesophageal reflux disease), food, and trauma. Reports were also reviewed for any statements regarding to the possible delayed absorption of alcohol. Table 1 shows a summary of the results.

Table 1.

Summary of retrograde extrapolation reports from the Minnesota BCA during 2023 and 2024.

Number	Assumed absorption ⩽ 2 hours	Considered: medications, food, medical conditions?	Considered: trauma?	The report states that absorption could be delayed?
36	36	0	1	1

All 36 reports assumed the subject was in the post-absorptive phase of alcohol elimination within 2 hours. No adjustments were made for food consumption, medications, trauma, or medical conditions. A single report mentioned that blood loss due to trauma could delay absorption of alcohol.

The practice of assuming complete alcohol absorption within 2 hours of a subject’s last drink reflects limitations in current professional guidance. For example, ANSI/ASB Best Practice Recommendation for Performing Alcohol Calculations in Forensic Toxicology acknowledges that ‘studies support that it can take up to 2 hours to reach the post-absorptive phase after the last drink’ and instructs scientists to assume a post-absorptive status ‘if the time of incident is more than 2 hours after the time of drinking cessation’. ⁴ While the ASB standard acknowledges that certain factors impact absorption rates, it does not provide a specific methodology for evaluating cases where factors may extend absorption beyond the 2-hour timeframe. Nor does the standard require a systematic assessment of case-specific variables that could substantially prolong absorption.

Pharmacokinetic evidence for extended absorption of alcohol

The human body’s absorption of alcohol follows well-established pharmacokinetic principles, yet these principles show immense individual variation that challenges a one-size-fits-all approach to forensic alcohol calculations.

The effect of food on alcohol absorption kinetics

Jones and Neri’s 1991 study provided evidence of how a large meal alters alcohol absorption. ⁵ When subjects consumed alcohol with a large meal, the absorption pattern became dramatically different from the familiar rapid-absorption curves seen in fasting studies. Rather than the typical quick rise to peak blood alcohol concentration, food created a complex, prolonged absorption process.

The most striking finding was that one subject didn’t reach peak alcohol concentration until 230 minutes, nearly 4 hours, after finishing his drinks. The researchers noted the vast degree of individual variation in absorption between subjects. They also documented a biphasic absorption pattern where a large amount of alcohol was absorbed relatively quickly, with the remaining alcohol trickling into the bloodstream over several hours. The authors noted the importance of using caution and considering individual variation when performing retrograde extrapolation analysis for legal purposes, stating:

The results presented in this paper emphasise the need for caution when engaging in retrograde extrapolation of BAC for legal purposes. In some individuals, the absorption of alcohol might proceed for several hours after the end of drinking.

A person who drinks with dinner and then drives 2 hours later may still be in the absorptive or plateau phase of the alcohol elimination curve. Traditional retrograde calculations assuming complete absorption within 2 hours would fundamentally mischaracterise such a scenario.

Inter-individual variability in absorption kinetics

Dubowski’s seminal 1985 review of alcohol pharmacokinetics documented a ‘14-fold variation between absorption times to peak blood alcohol concentrations’ even among healthy individuals. ⁶ Dubowski pointed to a study where peak concentrations occurred anywhere from 12 to 166 minutes after consumption of alcohol, the upper range, representing nearly 3 hours.

Dubowski also presented BAC time curves from another study, which showed significant inter-subject variability in time to reach peak alcohol concentration after drinking. He noted great variation in the absorption of alcohol amongst the subjects, with one subject taking approximately 3.25 hours to reach peak alcohol concentration.

Due to the large individual variation in alcohol absorption, Dubowski expressed scepticism towards the use of pharmacokinetic calculations for retrograde extrapolation estimates, stating ‘. . . no forensically valid forward or backward extrapolation of blood or breath alcohol concentrations is ordinarily possible in a given subject and occasion solely on the basis of time and individual analysis results’.

Pathophysiological conditions affecting absorption

Clinical conditions affecting gastrointestinal function introduce another layer of complexity to the alcohol absorption puzzle. Booker and Renfroe’s 2015 study of individuals with GERD revealed average peak BAC times of 3.5 hours (range: 120–300 minutes) compared to 2.5 hours (range: 100–240 minutes) in healthy controls. The study revealed how GERD can delay gastric emptying and alcohol absorption. Individuals with GERD experience delayed gastric emptying due to the pathophysiology of their condition, which keeps alcohol in the stomach longer before it reaches the small intestine. This delay translated into extended alcohol absorption timelines.

Other factors that delay alcohol absorption

The complexity of alcohol absorption becomes apparent when examining the numerous variables that can alter the timeline from consumption to peak BAC levels. One of the main drivers of alcohol absorption is the role of the pyloric sphincter in allowing alcohol into the small intestine, where a greater surface area allows for more rapid absorption. ⁷

Beverage characteristics add another layer of complexity to absorption predictions. Alcoholic beverages with sugary or carbohydrate content, such as beer, tend to delay alcohol absorption.^8–10 Very high alcohol concentrations may, paradoxically, delay gastric emptying due to changes in the stomach mucosa. ¹¹ Smoking cigarettes has been shown to delay absorption, ¹² as have anticholinergic medications that slow gastric emptying. ¹³ Additionally, trauma and blood loss can delay absorption. If unabsorbed alcohol remains in the stomach when trauma occurs, the reduced splanchnic circulation associated with haemorrhagic shock can delay alcohol absorption. ¹⁴

Emerging pharmacological considerations: GLP-1 receptor agonists

A new concern about the potential for delayed alcohol absorption involves the rapidly expanding use of GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), and tirzepatide (Mounjaro, Zepbound). Initially developed for diabetes management, these medications have gained widespread popularity for weight management, with millions of Americans and Europeans now using them.^15–17 Their use continues to expand to other diseases, including cardiovascular disease, obstructive sleep apnoea, liver disease and alcohol and nicotine dependence.^18,19

GLP-1 receptor agonists exert their therapeutic effects partly through gastroparesis, the deliberate slowing of gastric emptying. ²⁰ This mechanism, which helps patients feel full longer and eat less, could dramatically affect alcohol absorption kinetics. When gastric emptying is pharmacologically delayed, alcohol remains in the stomach longer before reaching the small intestine, where most absorption of alcohol occurs.^11,21 Indeed, an emerging investigation found that GLP-1 receptor agonists delayed the rise in breath alcohol concentration levels compared to controls. ²²

An individual using GLP-1 medications who consumes alcohol with a meal may experience prolonged alcohol absorption, potentially extending beyond the 2-hour absorption window typically considered. As GLP-1 receptor agonist use continues to expand, forensic toxicologists should consider the implications for these medications as they relate to pharmacokinetic calculations for alcohol.

Discussion

The common assumption amongst forensic toxicologists that alcohol absorption is always complete within 2 hours of drinking should be reconsidered. Performing retrograde analysis of alcohol while an individual is still in the absorptive phase will lead to erroneous high estimates of a person’s BAC. Pharmacokinetic calculations for alcohol should emphasise the importance of considering individual differences rather than relying solely on population averages.

Current practice, documented by the ASB guidelines for alcohol calculations, fails adequately to consider factors that may prolong absorption of alcohol beyond 2 hours. When forensic experts testify to specific BAC at particular times without acknowledging the substantial uncertainties involved, they may mislead legal decision-makers about the precision of such calculations.

Recommendations

Forensic toxicologists should evaluate each case for factors that may extend alcohol absorption beyond the conventional 2-hour timeframe. Detailed consumption history, including food intake, smoking, medical conditions, medications, and trauma, provides crucial context for retrograde extrapolation estimates.

When uncertainty exists regarding the state of absorption, forensic toxicologists should consider longer absorption windows based on case circumstances rather than defaulting to the ‘2-hour window’. Toxicologists should assess the limitations of retrograde extrapolation estimates when the absorption status remains unclear.

Reports regarding retrograde extrapolation should explicitly address assumptions regarding absorption timing rather than assuming a universal constant. Factors considered in determining post-absorptive status should be documented and justified. The limitations in calculations should be clearly stated rather than implied.

Conclusion

The human body does not operate according to arbitrary time limits. Individual physiological variation, combined with factors affecting alcohol absorption, demands that forensic toxicologists move beyond universal 2-hour assumptions regarding alcohol absorption. Evidence that alcohol absorption may extend 2–5 hours beyond the last drink in certain circumstances requires a more nuanced, case-specific approach to pharmacokinetic calculations for alcohol. Toxicologists performing retrograde extrapolation estimates should consider moving towards recognising individual variation as the norm, not the exception, in alcohol absorption kinetics.