Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery: Ethanol kinetics after gastric bypass

Department of Surgery, University Hospital, Orebro, Sweden.
British Journal of Clinical Pharmacology (Impact Factor: 3.88). 01/2003; 54(6):587-91. DOI: 10.1046/j.1365-2125.2002.01698.x
Source: PubMed


To investigate the absorption, distribution and elimination of ethanol in women with abnormal gut as a result of gastric bypass surgery. Patients who undergo gastric bypass for morbid obesity complain of increased sensitivity to the effects of alcohol after the operation.
Twelve healthy women operated for morbid obesity at least 3 years earlier were recruited. Twelve other women closely matched in terms of age and body mass index (BMI) served as the control group. After an overnight fast each subject drank 95% v/v ethanol (0.30 g kg-1 body weight) as a bolus dose. The ethanol was diluted with orange juice to 20% v/v and finished in 5 min. Specimens of venous blood were taken from an indwelling catheter before drinking started and every 10 min for up to 3.5 h post-dosing. The blood alcohol concentration (BAC) was determined by headspace gas chromatography.
The maximum blood-ethanol concentration (Cmax) was 0.741 +/- 0.211 g l-1 (+/- s.d.) in the operated group compared with 0.577 +/- 0.112 g l-1 in the controls (mean difference 0.164 g l-1, 95% confidence interval (CI) 0.021, 0.307). The median time to peak (tmax) was 10 min in the bypass patients compared with 30 min in controls (median difference -15 min (95% CI -10, -20 min). At 10 and 20 min post-dosing the BAC was higher in the bypass patients (P < 0.05) but not at 30 min and all later times (P > 0.05). Other pharmacokinetic parameters of ethanol were not significantly different between the two groups of women (P > 0.05).
The higher sensitivity to ethanol after gastric bypass surgery probably reflects the more rapid absorption of ethanol leading to higher Cmax and earlier tmax. The marked reduction in body weight after the operation might also be a factor to consider if the same absolute quantity of ethanol is consumed.

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    • "Conversely, reports of increased risk for ethanol (EtOH) consumption following RYGB have raised concerns that RYGB may increase the vulnerability for alcohol use disorder [9], [10]. Notably, RYGB patients have higher and longer-lasting blood EtOH concentrations, and a shorter period of onset than non-surgical controls when consuming similar amounts of EtOH [11], [12], [13], [14]. Changes in EtOH’s absorption and pharmacokinetics may alter not only the bioavailability and stimulating properties of EtOH on the brain, but also influence the neuronal and hormonal signals upstream of the reward system. "
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    ABSTRACT: Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV) administered ethanol (1%). For this purpose, high fat (60% kcal from fat) diet-induced obese male Sprague Dawley rats were tested ∼2 months after RYGB or sham surgery (SHAM) using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.
    PLoS ONE 12/2013; 8(12):e83741. DOI:10.1371/journal.pone.0083741 · 3.23 Impact Factor
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    • "However, other studies show no change in risk for alcohol following RYGB [20], [21]. However, the broader consensus is that RYGB patients have higher and longer-lasting blood alcohol concentrations, and a shorter period of onset than non-surgical controls when consuming similar amounts of ethanol [22], [23], [24], [25]. Changes in alcohol's pharmacokinetics may alter not only the bioavailability and stimulating properties of EtOH acting directly on the brain, but may also influence the neuronal and hormonal signals upstream of the reward system. "
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    ABSTRACT: Roux-en-Y gastric bypass (RYGB) is one of the most successful treatments for severe obesity and associated comorbidities. One potential adverse outcome, however, is increased risk for alcohol use. As such, we tested whether RYGB alters motivation to self-administer alcohol in outbred dietary obese rats, and investigated the involvement of the ghrelin system as a potential underlying mechanism. High fat (60%kcal from fat) diet-induced obese, non-diabetic male Sprague Dawley rats underwent RYGB (n = 9) or sham operation (Sham, n = 9) and were tested 4 months after surgery on a progressive ratio-10 (PR10) schedule of reinforcement operant task for 2, 4, and 8% ethanol. In addition, the effects of the ghrelin-1a-receptor antagonist D-[Lys3]-GHRP-6 (50, 100 nmol/kg, IP) were tested on PR10 responding for 4% ethanol. Compared to Sham, RYGB rats made significantly more active spout responses to earn reward, more consummatory licks on the ethanol spout, and achieved higher breakpoints. Pretreatment with a single peripheral injection of D-[Lys3]-GHRP-6 at either dose was ineffective in altering appetitive or consummatory responses to 4% ethanol in the Sham group. In contrast, RYGB rats demonstrated reduced operant performance to earn alcohol reward on the test day and reduced consummatory responses for two subsequent days following the drug. Sensitivity to threshold doses of D-[LYS3]-GHRP-6 suggests that an augmented ghrelin system may contribute to increased alcohol reward in RYGB. Further research is warranted to confirm applicability of these findings to humans and to explore ghrelin-receptor targets for treatment of alcohol-related disorders in RYGB patients.
    PLoS ONE 11/2012; 7(11):e49121. DOI:10.1371/journal.pone.0049121 · 3.23 Impact Factor
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    • "The education and guided discussion about alcohol and bariatric surgery covers specific information designed to inform patients about the possible risks. Patients are informed that alcohol might be much more intoxicating after surgery [4] [10], with a single glass of wine potentially putting some gastric bypass patients' alcohol levels over the legal driving limit of .08 [12]. We also note that bariatric patients can show different symptoms of intoxication (e.g., dizziness), and some might take almost twice as long to return to sobriety [12]. "
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    ABSTRACT: Established clinical guidelines identify current alcohol abuse and dependence as contraindications for weight loss surgery. However, guidance on how to best assess alcohol use in bariatric patients has not been elucidated. Furthermore, concerns with postoperative alcohol use/abuse and increased sensitivity warrant the development of recommendations on appropriate interventions for patients pursuing weight loss surgery. Our objective was to review the current data on bariatric surgery and substance abuse/addiction, with an emphasis on alcohol use, offer guidance on how to assess the risk of such problems, and provide preliminary recommendations on treating high-risk patients. The relevant published data on alcohol use, abuse, and dependence in pre- and postoperative bariatric patients was reviewed. Also, the putative mechanisms of increased alcohol sensitivity after weight loss surgery were examined. Although current alcohol abuse/dependence is less than that in population-base rates, bariatric surgery candidates have a greater history of alcohol use disorders. Physiologic changes after surgery can also change vulnerability to problematic alcohol use, and many patients continue to consume alcohol after surgery. Assessment techniques and strategies to provide informed consent and education on alcohol were included from the Bariatric and Metabolic Institute at the Cleveland Clinic. Weight loss surgery candidates might have a greater lifetime risk of alcohol use disorders and greater sensitivity to the intoxicating effects of alcohol after surgery. Adequate screening, assessment, and preoperative preparation could help mitigate this risk. Future research should examine the efficacy of such risk management strategies.
    Surgery for Obesity and Related Diseases 02/2012; 8(3):357-63. DOI:10.1016/j.soard.2012.01.016 · 4.07 Impact Factor
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