# Pharmacokinetics and Responses to Alcohol After Bariatric Surgery

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2023 · $371,756

## Abstract

ABSTRACT
More than two million Americans have undergone bariatric surgery over the last decade; given the obesity
epidemic, this number will continue to rise. Since 2018 of the ~ 250,000 yearly bariatric procedures performed
in the United States, 72% are sleeve gastrectomy (SG) and 21% Roux-en-Y gastric bypass (RYGB). Although
these surgeries provide the most successful long-term treatment for obesity, they double the risk of developing
alcohol use disorders (AUD). The precise mechanism(s) underlying an increase AUD risk is uncertain, but in
our previous NIH-funded research in women who underwent these surgeries (AA024103), we demonstrated
that both SG and RYGB cause profound changes in alcohol pharmacokinetics (PK) and sensitivity to the
subjective effects of alcohol; both of which can increase AUD risk. RYGB and SG doubled peak blood alcohol
concentrations when consuming the same dose as before surgery. By studying PK after SG, we also help
clarify that most alcohol first-pass metabolism (FPM) occurs in the stomach, not the liver (at least in women),
providing a plausible mechanism for increased alcohol-related liver disease and AUD after surgeries that
reduce the stomach. In people who did not undergo SG/RYGB, drinking alcohol with a meal increases FPM
and the alcohol elimination rate (AER), thus reducing alcohol bioavailability and intoxication. However, the
effects of food on alcohol PK after SG are unknown. SG alters nutrient absorption leading to earlier and higher
glycemic peaks concomitant with exaggerated postprandial insulin rises that can trigger postprandial
hypoglycemia. Because alcohol inhibits gluconeogenesis, we posit that drinking alcohol with food will increase
the risk for hypoglycemia after SG. In addition, there are remarkable sex-related differences in alcohol PK, but
previous bariatric studies included only women or very few men to determine sex differences. Therefore, the
primary goal of the proposed study is to determine sex-related differences in the impact of SG on the PK (Aim
1), subjective effects (Aim 2), and glycemic effects (Aim 3) in the fasted versus prandial state when alcohol is
ingested or given intravenously clamped (the gold standard to measure AER and acute alcohol tolerance). We
will use a cross-sectional study to compare participants who underwent SG surgery 1-5 years ago with
matched non-operated controls (both sexes). Our main hypotheses are that compared to controls, in the SG
group, food will 1) increase less FPM (particularly in men) and decrease less the sedative effects of ingested
alcohol, 2) amplify alcohol-hypoglycemia and acute tolerance to the sedative effects when alcohol is given IV
(in the clamp). This project will answer the questions of whether there are sex-related differences in the impact
of SG on alcohol’s PK and pharmacologic effects, whether drinking alcohol with a meal is effective or
counterproductive post-SG (considering risk for hypoglycemia) and clarify the site of FPM in men....

## Key facts

- **NIH application ID:** 10801349
- **Project number:** 2R01AA024103-07A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** MARTA YANINA PEPINO DE GRUEV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $371,756
- **Award type:** 2
- **Project period:** 2016-04-10 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801349

## Citation

> US National Institutes of Health, RePORTER application 10801349, Pharmacokinetics and Responses to Alcohol After Bariatric Surgery (2R01AA024103-07A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801349. Licensed CC0.

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