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CORK Bibliography: Absorption, Alcohol

57 citations. January, 1997 to present

Prepared: March 2008

Adams WL. Interactions between alcohol and other drugs. IN: Gurnack AM, ed. Older Adults' Misuse of Alcohol, Medicines, and Other Drugs. New York: Springer Publishing Co., 1997. pp. 185-205. (80 refs.)

This chapter begins with the epidemiological findings in respect to the use of alcohol among the elderly. It also discuss the mechanisms which can cause significant alcohol-drug interactions, including the process of metabolism, and aging related changes in pharmacology and absorption. The chapter also focuses upon the major adverse outcomes of alcohol-drug interactions including, altered blood levels of prescribed medications, lowered toxicity, GI system problems, and interference with the desired effects of prescribed drugs.

Baraona E. Site and quantitative importance of alcohol first-pass metabolism. Alcoholism: Clinical and Experimental Research 24(4): 405-406, 2000. (10 refs.)

This is one in a set of short papers that were presented at a workshop on issues relevant to the absorption, distribution, and elimination of alcohol in non-alcoholics. The meeting was convened by the National Institute on Alcohol Abuse and Alcoholism.

Cobaugh DJ; Gibbs M; Shapiro DE; Krenzelok EP; Schneider SM. A comparison of the bioavailabilities of oral and intravenous ethanol in healthy male volunteers. Academic Emergency Medicine 6(10): 984-988, 1999. (22 refs.)

Objectives: Ethanol (EtOH), the antidote for methanol and ethylene glycol, is administered by the oral (PO) and intravenous (IV) routes. Serum concentrations (SCs) of 100 mg/dL or more are targeted for clinical effect. This study was completed to validate the assumption that there are minimal differences in SC achieved between these two routes. Methods: Twenty healthy male volunteers were randomized to receive either PO or IV EtOH. Subjects abstained from EtOH for 48 hours before each phase. After a seven-day washout period, the subjects crossed over to the other group. Inclusion criteria were no history of medical problems, age between 21 and 40 years, and actual body weight within 10% of ideal weight. Baseline EtOH SCs were obtained before participation in each phase. Two hours after a standard breakfast, the subjects received 700 mg/kg of PO or IV EtOH. PO EtOH was administered as a 20% solution in juice over 10 minutes. IV EtOH, controlled by an infusion pump, was administered as a 10% solution over 30 minutes. Blood was drawn for EtOH SCs at 45, 75, 105, 135, 165, 225, 285, and 345 minutes after start of the dose. Results: All initial EtOH SCs were 0. EtOH SCs were higher after IV administration. Mean peak SC was 103.6 mg/dL after IV administration and 71.3 mg/dL after PO administration (p < 0.0001). Mean time to peak was 46.5 minutes after TV administration and 103.5 minutes after PO administration (p < 0.0001). Total area under the curve was 17,440 min-mg/dl after IV administration and 13,875 min-mg/dl after PO administration (p < 0.003). The order of treatments did not affect results (p > 0.1). Conclusion: Significant differences exist between the SCs of EtOH as well as the times to peak SC after PO and IV administrations.

Cole-Harding S; Michels VJ. Does expectancy affect alcohol absorption? Addictive Behaviors 32(1): 194-198, 2007. (12 refs.)

Many factors influence alcohol absorption, yet few studies have addressed the issue of whether or not experimental manipulations themselves may affect alcohol absorption. The current balanced placebo design study comparing the expectancy effects of root beer and non-alcoholic beer vehicles resulted in significantly lower blood alcohol levels in the root beer condition than in the beer condition even though alcohol doses were the same. Two possible explanations are discussed; differences in expectancy may have affected absorption, or fructose in the root beer may have slowed absorption of alcohol relative to the maltose in beer. The literature does not provide strong evidence for either of the hypotheses. The implication of this study's results is that alcohol absorption rate may be an important source of confounding effects in behavioral research in the laboratory, because it may be affected by beverages or other experimental conditions.

Desager JP; Golnez JL; De Buck C; Horsmans Y. Watercress has no importance for the elimination of ethanol by CYP2E1 inhibition. Pharmacology and Toxicology 91(3): 103-105, 2002. (16 refs.)

Watercress, a cruciferous vegetable, is known to inhibit the metabolism of several CYP2E1 substrates such as paracetamol and chlorzoxazone. Since ethanol and its metabolite, acetaldehyde, are CYP2E1 substrates, the influence of watercress on ethanol and acetaldehyde was investigated in healthy human volunteers. According to a randomized crossover design, ethanol and acetaldehyde pharmacokinetic parameters were determined in 9 persons at 3 occasions: without watercress and after watercress ingestion preceding ethanol consumption from 1 or 10.5 hr, respectively Ethanol t(max) occurred significantly later when watercress was ingested I hr before ethanol ingestion. Likewise, acetaldehyde C-max was significantly higher whereas acetaldehyde AUCs were increased by watercress but not significantly All other ethanol and acetaldehyde pharmacokinetic parameters were similar between the 3 treatments. In healthy volunteers, no major watercress effect was observed on ethanol clearance but a weak inhibiting effect on acetaldehyde metabolism is possible. Ethanol absorption is also delayed by single ingestion of watercress immediately preceding ethanol consumption.

Dettling A; Fischer F; Bohler S; Ulrichs F; Skopp G; Graw M et al. Ethanol elimination rates in men and women in consideration of the calculated liver weight. Alcohol 41(6): 415-420, 2007. (52 refs.)

The purpose of the study was to examine gender differences on the pharmacokinetics of ethanol. Sixty-eight healthy men and 64 healthy women with normal body mass indexes received between 0.79 and 0.95 g ethanol/kg body weight in the form of their choice after they had eaten a "typical" breakfast. The aimed concentration for both genders was a blood alcohol concentration C-0 of 0.104 g/dl. Blood samples in the elimination phase were taken in 10- to 20-min intervals beginning after completion of absorption. The maximum blood ethanol concentration was 0.0819 +/- 0.0184 g/dl for women and 0.0841 +/- 0.0155 g/dl for men. The hourly ethanol elimination rate, calculated over a linear function, in blood of 0.0179 +/- 0.0030 g/dl/h in women was significantly higher than the 0.0159 +/- 0.0029 g/dl/h for men (P <.0001). In relation to the liver weight, the hourly elimination rates were 5.008 +/- 0.678 g/kg liver/h for women and 4.854 +/- 0.659 g/kg liver/h for men, and were not statistically significant. The different liver masses as calculated in relation to the distribution volume account for the differing ethanol elimination rates between men and women.

Ely M; Hardy R; Longford NT; Wadsworth MEJ. Gender differences in the relationship between alcohol consumption and drink problems are largely accounted for by body water. Alcohol and Alcoholism 34(6): 894-902, 1999. (31 refs.)

It is widely reported that women drink less and have a lower prevalence of drink problems than men, but the gender differences in the relationship between level of drinking and drink problems have rarely been investigated quantitatively. This paper reports results from the Medical Research Council National Survey of Health and Development (the 1946 British Cohort) when the subjects were 43 years old. Using 7-day recall for alcohol consumption and CAGE scores of 2, 3 or 3 for drink problems. it was found that the prevalence of drink problems increased with level of alcohol consumption. Women were more likely than men to report drink problems at the same level of alcohol consumption. However this gender difference was largely accounted for by individual differences in weight of body water. Beer accounted for the excess of men's drinking over women's and the proportion of alcohol consumed as beer was inversely related to drink problems. Eighty per cent of women and 52% of men who had drink problems in the past year reported drinking less than an average of 3 U (women) or 4 U (men) a day in the past week. As drinking levels in women begin to approach those in men, rates of drink problems in women are likely to overtake those in men because of women's greater physiological sensitivity to the effects of alcohol.

Franke A; Nakchbandi IA; Schneider A; Harder H; Singer MV. The effect of ethanol and alcoholic beverages on gastric emptying of solid meals in humans. Alcohol and Alcoholism 40(3): 187-193, 2005. (15 refs.)

Aims: The systematic study of the effect of pure ethanol, alcoholic beverages, and their non-alcoholic components on gastric emptying of solid meals in humans. Methods: 16 fasting healthy male subjects received once weekly 300 ml of the following solutions in random order: 4 and 10% (v/v) ethanol, beer, red wine, 5.5 and 11.4% (w/v) glucose, and water. The test solutions were given either together with a low caloric (270 kcal, n = 8) or a high caloric (740 kcal, n = 8) solid meal. Ultrasonography of the antrum was used to determine gastric emptying. Results: Gastric half emptying time (t(1/2) ) of the high caloric solid meal with water was 131.3 +/- 7 min. The ingestion of 4 and 10% (v/v) ethanol (158.8 +/- 9.3 and 165.6 +/- 6.2 min, respectively), beer (163.1 +/- 11 min), and red wine (186.3 +/- 8.4 min) resulted in a significantly longer t(1/2) than water. The lag phases after 4 and 10% (v/v) ethanol, beer, and red wine were not significantly different from that of water (48.1 +/- 6.5 min). Compared with water, the ingestion of 5.5 and 11.4% (w/v) glucose resulted in a significantly longer t(1/2) (153.8 +/- 5 and 168.1 +/- 14.4 min, respectively) by increasing the duration of the lag phase. The high caloric meals resulted in a 2-fold prolongation of t(1/2) when compared with the low caloric meals. The effect of the solutions on the gastric emptying times, however, was similar for both test meals. Conclusions: (i) Ethanol in low concentrations of 4 and 10% (v/v) prolongs gastric emptying of solid meals; this inhibitory effect is not dose-dependent. (ii) Alcoholic beverages (beer and red wine) also result in a prolongation of gastric emptying. The inhibitory effect of red wine, but not of beer, is more pronounced than that of the corresponding ethanol concentration and amount. (iii) The inhibitory effect of ethanol and alcoholic beverages is mainly induced by a prolongation of the gastric emptying phase (without affecting the lag phase), whereas 5.5 and 11.4% (w/v) glucose prolong the lag phase in a dose-dependent manner. (iv) The inhibitory effect of ethanol, beer, and red wine on gastric emptying does not depend on the caloric content of the meal.

Gaulier JM; Merle G; Lacassie E; Courtiade B; Haglund P; Marquet P et al. Fatal intoxications with chloral hydrate. Journal of Forensic Sciences 46(6): 1507-1509, 2001. (23 refs.)

This article reports toxicological findings in two fatalities after voluntary ingestion of chloral hydrate, a sedative-hypnotic drug. The first case, an alcohol-dependent man treated with chloral hydrate syrup to which he was dependent, was discovered comatose and in respiratory arrest. Death occurred on the 9th day of hospitalization following cerebral edema. The second case, an alcohol-dependent woman who was depressed and epileptic, was admitted to the intensive care unit with heart and respiratory failure following chloral hydrate absorption. She died 3 days later after a deep coma. In these two cases, chloral hydrate intoxication was confirmed by toxicological analysis: chloral hydrate and its major metabolite trichloroethanol were identified and determined in serum and urine using headspace capillary gas chromatography-mass spectrometry. The concentrations measured were compared with those found in previously published fatalities. The analytical method used can be proposed for both clinical and forensic cases.

Gentry RT. Determinants and analysis of blood alcohol concentrations after social drinking. Alcoholism: Clinical and Experimental Research 24(4): 399-399, 2000. (0 refs.)

This is an introduction to a series of short papers that were presented at a workshop on issues relevant to the absorption, distribution, and elimination of alcohol in non-alcoholics. The meeting was convened by the National Institute on Alcohol Abuse and Alcoholism.

Gentry RT. Effect of food on the pharmacokinetics of alcohol absorption. Alcoholism: Clinical and Experimental Research 24(4): 403-404, 2000. (10 refs.)

Giancola PR; Zeichner A. The biphasic effects of alcohol on human physical aggression. Journal of Abnormal Psychology 106(4): 598-607, 1997. (94 refs.)

The authors assessed the biphasic effects of alcohol on human physical aggression. Sixty male social drinkers were assigned to 1 of 4 groups: alcohol ascending limb (AAL), alcohol descending limb (ADL), or 1 of 2 sober control groups. Aggression was assessed in the AAL and ADL groups at respective ascending or descending blood alcohol concentrations (BAG) of 0.08%. Each participant in the control groups was respectively yoked with a participant in either the AAL, or the ADL group to control for the longer period of time needed to reach a BAC of 0.08% on the descending limb compared with the ascending limb (i.e., passage of time effect). The authors measured aggression using a modified version of the Taylor aggression paradigm (S. Taylor, 1967), in which electric shocks are received from and administered to a fictitious opponent during a competitive task. The AAL group was more aggressive than the ADL group. There were no differences between the ADL group and the control groups, which suggests that alcohol does not appear to increase aggression on the descending limb. The control groups did not differ in aggression, thus ruling out a passage of time effect.

Haber PS. Metabolism of alcohol by the human stomach. Alcoholism: Clinical and Experimental Research 24(4): 407-408, 2000. (11 refs.)

Hahn RG; Norberg A; Jones AW. 'Overshoot' of ethanol in the blood after drinking on an empty stomach. Alcohol and Alcoholism 32(4): 501-505, 1997. (12 refs.)

The time required for ethanol to distribute between the systemic circulation and the rest of the body water results in an 'overshoot' of the blood-alcohol concentration (BAG) during the first 30 min. after intravenous infusion. To investigate whether a similar distribution phenomenon occurs when ethanol is given by the oral route, we compared BACs after intravenous infusion and oral intake under strictly controlled conditions by giving a 0.4 g/kg dose of ethanol over 15 min. to six fasting female volunteers. The results show an 'overshoot' in three volunteers who had the shortest time to BAC (max), which indicates rapid absorption, and the time-course was similar to the distribution phase seen during the intravenous experiments. We conclude that BAC is sometimes higher than expected shortly after alcohol has been ingested rapidly. This finding can probably be explained by the fact that ethanol is distributed more slowly throughout the total body water than it is absorbed from the gut.

Hamid A; Kaur J. Long-term alcohol ingestion alters the folate-binding kinetics in intestinal brush border membrane in experimental alcoholism. Alcohol 41(6): 441-446, 2007. (29 refs.)

The folic acid transport across epithelial cell membrane of the intestine is an essential step for its absorption, conservation, and homeostasis in the body. In this study, we sought to examine the kinetics of binding to intestinal brush border membrane (BBM) considering intestinal malabsorption as the major contributing factor to alcohol-induced folate deficiency. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months. We studied [H-3]-folic acid binding to the intestinal BBM and acidic pH-dependent binding was observed to be associated with reduced maximal binding (B-max) in chronic ethanol-fed group. However, under such conditions, there was no significant effect of ethanol ingestion on K-d and pH optimum of the binding process. Increasing the osmolarity at pH 5.5 had no effect on the binding of folate to BBM, thus confirming that the observed changes in B,m values were due to site-specific binding to the extravesicular sites. Importantly, ethanol ingestion disturbs the S-S status at the binding site besides interfering with the Na+ and divalent cation dependency of the binding process. These results highlight the possible mechanism of folate malabsorption at primary absorptive site during alcoholism.

Hernandez-Collados A; Sanchez-Turet M; Sanchez-Sastre J. Different cognitive effects in the increasing and decreasing limb of the metabolic curve of ethanol. Medical Science Research 26(3): 173-175, 1998. (24 refs.)

39 healthy subjects (20 men and 19 women) received a single dose of ethanol (1 g/kg). We used the Benton test to assess differences in performance during absorption and elimination phases of ethanol. In the absorption phase, at a mean blood alcohol concentration (BAC) of 0.24 g/l, the subjects' performance decreased significantly. This impairment was related to perceptual-motor and visual memory processes. In the elimination phase, at a mean BAC of 0.47 g/l, there was no decrease in performance. We may conclude that behaviour was different in the ascending and descending phases. It is therefore necessary to differentiate the alcohol metabolization phases in future studies.

Holford NHG. Complex PK/PD models: An alcoholic experience. International Journal of Clinical Pharmacology and Therapeutics 35(10): 465-468, 1997. (6 refs.)

The absorption and disposition of ethanol are among the more complex of challenges for pharmacokinetics. Attempts to explain the relative bioavailability of ethanol in beer of differing ethanol concentrations have led to models of first pass extraction which recognize the concentration dependent nature of ethanol elimination as well as the role of hepatic blood and the rate of absorption from the gut. The pharmacodynamics of ethanol have also proven to be of matching complexity. While effects on motor coordination only required a delay between plasma and response time profiles the effects on a cognitive test revealed the rapid development of tolerance in addition to a delay, Description of the time course of ethanol effects in an individual after a single oral dose requires over 10 parameters and offers a serious challenge for forensic predictions.

Hunt WA. Pharmacology of alcohol. IN: Tarter RE; Ammerman RT; Ott PJ, eds. Handbook of Substance Abuse. New York: Plenum Publishing Co., 1998. pp. 7-21. (97 refs.)

Following a brief introduction outlining the dimensions of alcohol problems, this chapter discusses the chemical properties, absorption, distribution, metabolism and elimination of alcohol. It then turns to examination of the behavioral effects, namely intoxication, tolerance, and dependence. The mechanisms of action are then discussed, along with the membrane effects, and neurotransmitters and the response to alcohol, including dopamine, serotonin, the opioid peptides, GABA, glutamate, second messengers. In conclusions the neurotransmitter/effector interactions are considered along with the implications for treatment.

Ito A; Moriya F; Ishizu H. Estimating the time between drinking and death from tissue distribution patterns of ethanol. Acta Medica Okayama 52(1): 1-8, 1998. (20 refs.)

To establish a method for estimating the time between the last consumption of alcohol and death, we examined the ethanol levels in body fluids and tissues of rats that had been orally administered 1 g/kg ethanol. We observed the following relationships between ethanol levels in the cardiac blood (blood in the heart itself), vitreous humor, and urine: cardiac blood > vitreous humor > urine at 10 min (early absorption stage); vitreous humor > cardiac blood > urine from 20 to 50 min (late absorption stage); vitreous humor > urine > cardiac blood from 60 to 120 min (distribution stage); and urine > vitreous humor > cardiac blood at 180 min (excretion stage). It was also observed that, in cases of death immediately following drinking, ethanol levels in the stomach contents are very high, and the following ratios of ethanol levels were observed: skeletal muscle to cardiac blood - less than 1; liver to cardiac blood - around 1; buccal mucosa to cardiac blood - greater than 1. These ratios at equilibrium after drinking were around 1, lower than 1 and around 1 respectively. We also measured alcohol levels the cardiac blood, urine, vitreous humor and stomach contents of nine cadavers who had consumed alcohol prior to death, The relationships between the time since last consumption of alcohol and relative ethanol levels in these specimens were in good accordance with the results of the animal experiments.

Jones AW. Aspects of in-vivo pharmacokinetics of ethanol. Alcoholism: Clinical and Experimental Research 24(4): 400-402, 2000. (12 refs.)

Jones W; Fransson M; Andersson L. Evidenzer: A new breath-alcohol analyzer for evidential testing. Glasgow: ICADTS, 2004. (11 refs.)

This paper reports on the experience in Sweden which recently switched to a new evidential breath-alcohol analyzer (the Evidenzer) with the capability of use at a police station and also in a vehicle at the roadside. The advantages of the new system for analysis is presented. The paper reports on experience with 20 volunteers involved in drinking under controlled conditions, with testing at fixed intervals for up to 4 hours. It reports on the agreement between the two breath-alcohol instruments.

Jones AW; Holmgren P. Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism. Forensic Science International 135(3): 206-212, 2003. (31 refs.)

Concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N = 628) or chronic alcoholism (N = 647). In alcohol poisoning deaths both UAC and BAC were higher by about 2 g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74 g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18 +/- 0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74 g/l (N = 457) the mean S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30 +/- 0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74 g/l (N = 190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r = 0.84, residual S.D. = 0.47 g/l) and in chronic alcoholism deaths (r = 0.95, residual S.D. = 0.41 g/l). For both causes of death (N = 1275), the correlation between BAC and UAC was r = 0.95 and the residual S.D. was 0.46 g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18: 1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30: 1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.

Kalant H. Effects of food and body composition on blood alcohol curves. Alcoholism: Clinical and Experimental Research 24(4): 413-414, 2000. (9 refs.)

Kechagias S; Jonsson KA; Franzen T; Andersson L; Jones AW. Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease. Journal of Forensic Sciences 44(4): 814-818, 1999. (30 refs.)

Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (similar to 0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. An attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt. Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) or a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same or higher than venous BAC (mg/dL). Ln the post-peak phase, the BAC always exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5-min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable

Kechagias S; Jonsson KA; Jones AW. Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride. British Journal of Clinical Pharmacology 48(5): 728-732, 1999. (22 refs.)

Aims: To examine the influence of cisapride on the pharmacokinetics of ethanol and the impact of gastric emptying monitored by the paracetamol absorption test. Methods: Ten healthy male volunteers took part in a cross-over design experiment. They drank a moderate dose of ethanol 0.30 g kg(-1) body weight exactly 1 h after eating breakfast either without any prior drug treatment or after taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption of ethanol to monitor gastric emptying. Venous blood was obtained at 5-10 min intervals for determination of ethanol by headspace gas chromatography and paracetamol was analysed in serum by high performance liquid chromatography (h.p.l.c.). Results: The maximum blood-ethanol concentration (C-max) increased from 3.8 +/- 1.7 to 5.6+/-2.3 mmol l(-1) (+/- s.d.) after treatment with cisapride (95% confidence interval CI on mean difference 0.28- 3.28 mmol l(-1)). The area under the blood-ethanol curve (AUC) increased from 6.3 +/- 3.5 to 7.9 +/- 2.6 mmol l(-1) h after cisapride (95% CI -0.74-3.9 mmol l(-1) h). The mean blood ethanol curves in the cisapride and no-drug sessions converged at approximate to 2 h after the start of drinking. Both C-max and AUC were highest when the ethanol was ingested on an empty stomach (C-max 9.5 +/- 1.7 mmol l(-1) and AUC 14.6 +/- 1.9 mmol l(-1) h), compared with drinking 1 h after a meal and regardless of pretreatment with cisapride. Conclusions: A small but statistically significant increase in C-max occurred after treatment with cisapride owing to faster gastric emptying rate as shown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in C-max and AUC, was greatest after drinking the alcohol on an empty stomach. The cisapride-ethanol interaction probably lacks any clinical or forensic significance.

Kinoshita H; Ijiri I; Ameno S; Kubota T; Zhang X; Hishida S; Ameno K. Cholinergic nerves mediate acetaldehyde action in the gastrointestinal tract. Alcohol and Alcoholism 36(5): 377-380, 2001. (23 refs.)

The regulation mechanism of inhibition of intestinal ethanol absorption induced by high acetaldehyde (AcH) concentration in blood was investigated. We used atropine (AT), atropine methylbromide (ATMB), pirenzepine (PI), bethanechol (BE) and pilocarpine (PL) with or without cyanamide (CY; a potent inhibitor of aldehyde dehydrogenase, which induces high AcH concentration in blood). The K- a (absorption rate constant) value after the CY-alone pretreatment was significantly lower than that in controls. In the high AcH- induced cases, the values of K-a in AT and ATMB pretreatments were similar to controls, but the value of K-a in PI pretreatment was lower than that in controls. The values of K-a in the case of BE pretreatment with and without high AcH levels were lower than in controls. The K-a value in the PL with CY was significantly lower than that with CY alone. However, its action was blocked by ATMB pretreatment. These results suggest that high blood AcH concentrations inhibit intestinal ethanol absorption through the peripheral cholinergic nerves via muscarinic receptors, except for the muscarinic M-1 receptor, compared to other subtypes of muscarinic receptors.

Klockhoff H; Naslund I; Jones AW. Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery. British Journal of Clinical Pharmacology 54(6): 587-591, 2002. (30 refs.)

Aims: 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. Methods: 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. Results: The maximum blood-ethanol concentration (C (max) ) 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 (t (max) ) 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). Conclusions: The higher sensitivity to ethanol after gastric bypass surgery probably reflects the more rapid absorption of ethanol leading to higher C-max and earlier t(max) . 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.

Labianca DA. Variables that impact on the results of breath-alcohol tests. (letter). Journal of Chemical Education 81(10): 1420-1421, 2004. (0 refs.)

This letter comments on an earlier article by Kniesel and Bellamy (80:1448-1450, 2003) which mis-characterized a ratio as "breathe to blood" when in fact it is the reverse. There is also a correction of the amount of time required to avoid contamination of a breath sample by mouth-alcohol contents. The time required is not 5 minutes as noted in the article by closer to 20, which in fact is incorporated into the laws of the State of New York, for example.

Komura S; Fujimiya T; Yoshimoto K. Fundamental studies on alcohol dependence and disposition. Forensic Science International 80(1/2): 99-107, 1996. (37 refs.)

This article reviews some recent studies on alcohol preference, dependence, metabolism and pharmacokinetics which were mainly carried out in our department. The inbred strains of mice with genetically different alcohol drinking behavior and alcohol animal model treated with the neurotoxins, 6-hydroxydopamine and 5, 7-dihydroxytryptamine, are useful for a behavioral and pharmacological approach to evaluate the contribution of specific neural systems to alcohol, drug dependence mechanism and alcohol drinking behavior. The relations between alcohol preference and some physiological conditions are reviewed. On the drug-alcohol interaction, some drugs containing the chemical group =CHONO(2), antimony and methamphetamine are addressed. This article also deals with recent topics in the pharmacokinetics and pharmacodynamics of alcohol. The dose-dependency of the alcohol elimination rate, the first-pass metabolism during alcohol drinking, and the pharmacodynamic model for describing pulse rate reaction to plasma acetaldehyde are discussed.

Labianca DA. Variables that impact on the results of breath-alcohol tests. (letter). Journal of Chemical Education 81(10): 1420-1421, 2004. (0 refs.)

This letter comments on an earlier article by Kniesel and Bellamy(80:1448-1450, 2003) which mis-characterized a ration as "breathe to blood"when in fact it is the reverse.There is also a correction of the amount of time required to avoid contamination of a breath sample by mouth-alcohol contents.The time required is not 5 minutes as noted in the article by closer to 20, which in fact is incorporated into the laws of the State of New York, for example.

Lands WEM. A review of alcohol clearance in humans. (review). Alcohol 15(2): 147-160, 1998. (134 refs.)

The level of blood or brain alcohol is considered to influence alcohol ingestion by causing subjective perceptions or neural activations that are reinforcing or rewarding. Alcohol-dependent people may try to maintain some desired tissue level, drinking o replace the millimolar levels that were cleared from the blood by metabolism. The biomedical literature describes many approaches to understanding the role of blood alcohol levels in human physiology and behavior, and this review examines some of the published results. They include the general kinetics of intake and removal of beverage alcohol as well as the characteristics of many different catalysts that can interact with alcohol. Because ingested alcohol creates blood levels that are a 1000-fold greater than those normally experienced during abstinence, ethanol may impose itself as an alternate substrate for the many oxidoreductases that act physiologically on other endogenous alcohols. Many enzymes that can act on millimolar ethanol have been isolated, and their structural genes are sequenced. Unfortunately the genetic sequence does not indicate the physiological material upon which the translated gene product may act. In a sense, the set of enzymes with catalytic sites occupied by millimolar ethanol during alcohol drinking might constructively be regarded as {"orphan gene products" whose physiological role remains to be clarified. This review is designed to indicate some of what is known, what is not known, and what needs to be known to improve interpretations regarding adaptations to beverage alcohol and the ability of millimolar levels of alcohol to diminish dysphoria. The dysphoria may be influenced by ethanol metabolites, or by altered metabolism of currently unspecified endogenous substrates. A major challenge is to evaluate the multiple alternative variables within a context that stimulates curiosity and encourages quantitative tests of the relative contribution of each variable to the overall physiology of an individual.

Levine B; Smialek JE. Status of alcohol absorption in drinking drivers killed in traffic accidents. Journal of Forensic Sciences 45(1): 3-6, 2000. (11 refs.)

One issue which constantly confronts the forensic toxicologist in drinking driver cases is the relationship between the breath or blood alcohol concentration (AC) of the driver at the time of an event such as a traffic stop or an accident and the AC measured at a time subsequent to the event. In theory, the AC can be rising, on a plateau or declining at the time of the event. Several studies have indicated that the overwhelming majority of drinking drivers are on a plateau or are post-absorptive at the time of the event. In this study, driver fatality cases investigated by the Office of the Chief Medical Examiner, State of Maryland during a three-year period were reviewed. Included in this study were cases positive for alcohol in the blood at a cutoff of 0.01 g/dL and death occurring within 15 min of the accident. In fact, many of these deaths were instantaneous or near instantaneous based on the injuries documented by the medical examiner at autopsy. The blood and urine were analyzed for alcohol by head-space gas chromatography and urine AC to blood AC ratios were calculated. A total of 129 cases were included in this study. Eleven of the 129 cases (8.5%) had urine to blood AC ratio less than 1.0. It is likely that these individuals were in the absorptive phase at the time that the accident occurred. Thirty-two cases had a urine to blood AC ratio between 1.0 and 1.2 inclusive. In these cases, the subject could be viewed as in the plateau phase of the blood AC versus time curve. The remaining 86 cases had a urine to blood AC ratio greater than 1.2. This suggests that these individuals were in the post-absorptive state at the time of the accident. The information acquired from this study provides additional evidence to support the notion that the vast majority of individuals are not in the absorptive phase at the time of a traffic stop or an accident

Levitt MD; Levitt D. Use of a two-compartment model to predict ethanol metabolism. Alcoholism: Clinical and Experimental Research 24(4): 409-410, 2000. (4 refs.)

Lieber CS. Ethnic and gender differences in ethanol metabolism. Alcoholism: Clinical and Experimental Research 24(4): 417-418, 2000. (16 refs.)

Lindberg M; Olsson SG. Estimation of the level of arterial blood alcohol from analysis of breath: Investigation of a new more accurate technique than current methods. Glasgow: ICADTS, 2004. (0 refs.)

This paper considers the issues related to the determination of alcohol concentration in venous blood, as it involves an inherent non-systematic error due to variable absorptiopn, distriution and elimination in the tissues drained by the particular sampling vein. Thus its use can be disputed. Venous blood conent is lower than arterial content during the initial uptake phase whereas the reverse is true during elimination. The authors report on methods to validate blood alcohol from arterial, venous, and breath analysis.

Littleton J; Little H. Interactions between alcohol and nicotine dependence: A summary of potential mechanisms and implications for treatment. Alcoholism: Clinical and Experimental Research 26(12): 1922-1924, 2002. (8 refs.)

This article summarizes the potential mechanisms which underlie the interactions between alcohol and nicotine dependence. There is discussion of pharmacokinetic interactions that influence metabolism, absorption, and distribution. Also liver metabolism of both drugs may be altered through cytochrome induction after long-term exposure to both. There are also factors at the molecular level that need be considered, the impact on various neurotransmitters, and alcohol's effects on nicotinic receptors. It is also noted that, in contradistinction to the view that specific mechanisms are causal to the use of both drugs, there is the view that the phenomenon may be more indicative of a functional interaction. For example, possibly the cognitive enhancing effects of nicotine may offset the cognitive inhibition resulting from alcohol use. The role of conditioning in this phenomenon is reviewed. The author notes in conclusion, that whatever the basis the strength of dependence is greater among co-abusers.

Lukas SE; Orozco S. Ethanol increases plasma Delta(9)-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers. Drug and Alcohol Dependence 64(2): 143-149, 2001. (36 refs.)

Marihuana and alcohol are often used together, yet little is known about why they are combined. Male volunteers were assigned to one marihuana treatment group (placebo, low or moderate dose Delta (9)- tetrahydrocannabinol (THC)) and, on three separate study days, they also drank a different dose of ethanol (placebo, 0.35 or 0.7 g/kg). Plasma THC levels and changes in subjective mood states were recorded for 90 min after smoking. For many of the drug combinations, when subjects consumed ethanol they detected marihuana effects more quickly, reported more episodes of euphoria and had higher plasma THC levels than when they consumed placebo ethanol. These data suggest that ethanol may increase the absorption of THC resulting in an increase in the positive subjective mood effects of smoked marihuana and contributing to the popularity of this drug combination.

Martin CS; Balaban CD; McBurney DH. Tonic and phasic processes in the acute effects of alcohol. Experimental and Clinical Psychopharmacology 14(2): 209-218, 2006. (30 refs.)

This article presents a novel method for measuring the acute effects of alcohol. One hundred twenty nonproblem drinkers aged 21-28 participated in 3 alcohol administration sessions that produced peak blood alcohol concentrations (BACs) near .09 g%. Subjective intoxication ratings were taken at multiple points across rising and falling BACs. Mathematical modeling techniques decomposed intoxication ratings into a tonic component sensitive to BAC level and a phasic component sensitive to BAC rate of change. This model provided a good fit to observed data. Tonic and phasic gain parameters showed high repeatability across sessions. The average phasic gain parameter was about 4 times larger than the average tonic gain parameter, indicating that subjective intoxication is usually more affected by BAC change than by BAC level. The associations of drinking practices with tonic and phasic gain parameters varied by gender and family history of alcoholism. Tonic-phasic modeling allows individual and group differences in the acute effects of alcohol to be studied as time-dynamic processes.

Mason BJ; Goodman AM; Dixon RM; Hameed MHA; Hulot T; Wesnes K et al. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology 27(4): 596-606, 2002. (71 refs.)

Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials. There is scientific and clinical interest in evaluating these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes. Thus, this is the first human pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Twenty-four normal, healthy adult volunteers participated in a double-blind, multiple dose, within subjects, randomized, 3-way crossover drug interaction study of the standard therapeutic dose of acamprosate (2 g/d) and the standard therapeutic dose of naltrexone (50 mg/d), given alone and in combination, with seven days per treatment condition and seven days washout between treatments. Blood samples were collected on a standardized schedule for pharmacokinetic analysis of naltrexone, 6-beta-naltrexol, and acamprosate. A computerized assessment system evaluated potential drug effects on cognitive functioning. Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate, as indicated by an average 33% increase in acamprosate-maximum plasma concentration, 33% reduction in time to maximum plasma concentration, and 25% increase in area under the plasma concentration-time curve. Acamprosate did not affect the pharmacokinetic parameters of naltrexone or 6-beta-naltrexol. A complete absence of negative interactions on measures of safety and cognitive function supports the absence of a contraindication to co-administration of acamprosate and naltrexone in clinical practice.

Meier P; Seitz HK. Age, alcohol metabolism and liver disease. Current Opinion in Clinical Nutrition and Metabolic Care 11(1): 21-26, 2008. (43 refs.)

Purpose of review: Alcohol consumption among the elderly has increased. Alcohol metabolism changes with age and the elderly are more sensitive to the toxic effects; this increased consumption is therefore of great clinical relevance. Recent findings: Metabolism of ethanol changes with advancing age because activity of the enzymes involved, such as alcohol and acetalclehyde dehydrogenase and cytochrome P-4502E1, diminish with age. The water distribution volume also decreases with age. Both lead to increased blood concentrations of ethanol. Also, elderly people take more drugs, and ethanol and these drugs may interact; therefore, alcohol consumption can modify serum drug concentrations and their toxicity. Finally, elderly people may suffer more frequently from other types of liver disease, and alcohol may exacerbate these. Summary: Over recent decades alcohol consumption has increased among those who are older than 65 years. Alcohol is more toxic in the ageing organism because of changes in its metabolism, distribution and elimination, which lead to central nervous system effects at lower levels of intake; also, ageing organs such as brain and liver are more sensitive to the toxicity of alcohol. For these reasons, alcohol should be used in moderation, especially among those of older age.

Mezey E. Influence of sex hormones on alcohol metabolism. Alcoholism: Clinical and Experimental Research 24(4): 421-421, 2000. (5 refs.)

Mumenthaler M; Taylor J; O'Hara R; Yesavage J. Gender differences in moderate drinking effects. Alcohol Research & Health 23(1): 55-64, 1999. (63 refs.)

Women appear to become more impaired than men after drinking equivalent amounts of alcohol, achieving higher blood alcohol concentrations even when doses are adjusted for body weight. This finding may be attributable in part to gender differences in total body water content. Men and women appear to eliminate approximately the same total amount of alcohol per unit body weight per hour. However, women seem to eliminate significantly more alcohol per unit of lean body mass per hour than men. Some studies report that women are more susceptible than men to alcohol-related impairment of cognitive performance, especially in tasks involving delayed memory or divided attention functions. Psychomotor performance impairment, however, does not appear to be affected by gender. This article provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent studies on gender differences in alcohol absorption, distribution, elimination, and impairment. Speculation that gender differences in alcohol pharmacokinetics or alcohol-induced performance impairment may be caused by the menstrual cycle and variations in female sex hormones are discussed. It is concluded that the menstrual cycle in unlikely to influence alcohol pharmacokinetics.

Public Domain

Norberg A; Bratteby LE; Gabrielsson J; Jones AW; Fan H; Hahn RG. Do ethanol and deuterium oxide distribute into the same water space in healthy volunteers? Alcoholism: Clinical and Experimental Research 25(10): 1423-1430, 2001. (43 refs.)

Background: The volume of distribution at steady state for ethanol (V- ss) is thought to be identical to the total body water (TBW). We compared a two-compartment pharmacokinetic model with parallel Michaelis-Menten and first-order renal elimination with the classical one-compartment zero-order elimination model. Ethanol concentration- time profiles were established for breath, venous blood, and urine. The values of V-ss obtained for ethanol were compared with TBW determined by deuterium oxide dilution. Methods: Sixteen healthy volunteers each received a 30-min intravenous infusion of ethanol on two occasions. Ethanol was measured in breath by a quantitative infrared analyzer and in blood and urine by headspace gas chromatography. Deuterium oxide was given as an intravenous injection and measured in serum by isotope-ratio mass spectrometry. Components of variation were calculated by ANOVA to determine the precision of the estimates of V-ss and TBW. Results: Mean TBW, determined by deuterium oxide dilution, was 44.1 +/-3.9 liters ( SD) for men, corresponding to 0.61 liters/kg, and 37.4 +/-3.2 liters for women, or 0.54 liters/kg. Estimates of V-ss from blood-ethanol pharmacokinetics were 87.6% of TBW according to isotope dilution and 84.4% for breath analysis with the two- compartment model. This compares with 95.1% and 95.4% for blood and breath alcohol, respectively, when the classical zero-order kinetic analysis is used. The precision of the estimates of V-ss and TBW was between 1.56 and 2.19 liters (95% confidence interval). Conclusions: Ethanol does not distribute uniformly into the TBW. The precision of measuring V-ss by ethanol dilution was comparable to estimates of TBW by isotope dilution. Results of noninvasive breath ethanol analysis compared well with use of venous blood for estimating V-ss. The sophisticated two-compartment model was much superior to the classical one-compartment model in explaining the total concentration-time course of intravenously given ethanol.

Pavlic M; Libiseller K; Grubwieser P; Ulmer H; Sauper T; Rabl W. Another 'soberade' on the market: does Outox keep its promise? Wiener Klinische Wochenschrift 119(3-4): 104-111, 2007. (33 refs.)

Objective: Several products are being widely promoted for reduction of the concentration of alcohol in the human body. One of these preparations, the fructose soft drink Outox, claims to noticeably increase the alcohol elimination rate (beta 60). Theories to explain this 'fructose effect' are based on the assumption that NAD+, the coenzyme for alcohol dehydrogenase, is regenerated faster in the presence of fructose. Method: A randomized double-blind, placebo-controlled cross-over study was performed with 30 volunteers in two drinking sessions each. Under strictly identical conditions, the same amount of alcohol was consumed, followed by the consumption of either 250 ml Outox or 250 ml placebo. Periodical measurements of blood (BAC), breath (BrAC) and urine alcohol concentration (UAC) were performed. Results: Analyses revealed a significant difference (P < 0.0001) between the mean alcohol levels of the Outox and the placebo drinking sessions. The overall mean BAC difference was 0.077 g/l (BAC 0.748 g/l without vs 0.671 g/l with Outox), equivalent to 10.3%. The mean BrAC difference was 0.045 mg/l (BrAC 0.314 mg/l without vs 0.269 mg/l with Outox), equivalent to 14.3%. Differences were lower for women than for men. A significant difference between the alcohol elimination rates (beta 60) was not found. Conclusions: The results show that the soft drink Outox may decrease the alcohol concentration by about 10%. However, BAC and BrAC differences are rather a consequence of slower gastric absorption of alcohol, because Outox does not increase the alcohol elimination rate. Our study demonstrates that the claim of Outox or other fructose drinks to work as a 'soberade' cannot be proven from a scientific point of view. It should be the task of physicians to warn potential consumers, especially in connection with drinking and driving.

Pendlington RU; Whittle E; Robinson JA; Howes D. Fate of ethanol topically applied to skin. Food and Chemical Toxicology 39(2): 169-174, 2001. (7 refs.)

Driving a vehicle while having a blood alcohol concentration (BAC) higher than 80 mg/100 ml is illegal in the United Kingdom. Because future legislation might significantly reduce the legal BAC limit, the authors assessed the potential systemic dose of ethanol from using alcohol-based aerosol sprays by measuring the evaporation of carbon 14-labeled ethanol from the skin surface, the in vitro penetration of ethanol through excised pig skin, and the BAC of human volunteers (N = 16) after simulated use of an alcohol-based deodorant spray. Evaporation rates from polyethylene backed paper and whole pig skin were similar (t1/2 = 13.6 sec and 11.7 seconds respectively) while that from glass was longer (t1/2 = 24.8 seconds). Ethanol penetrated pig skin at a faster rate in occluded cells than in non-occluded cells (2.19 mg/square cm and 0.10 mg/square cm in 24 hours respectively). At the maximum flux seen in this experiment under occlusion, the amount of ethanol penetrating from a 1 square-meter area of skin would result in a BAC of about 4 mg percent in a 70-kg man. No alcohol was detectable in any of the blood samples taken from 16 human volunteers after they used an alcohol-based spray. The findings indicate that formulations that deliver ethanol to the skin are highly unlikely to result in a significant BAC in the user.

Quinn DI; Wodak A; Day RO. Pharmacokinetic and pharmacodynamic principles of illicit drug-use and treatment of illicit drug-users. Clinical Pharmacokinetics 33(5): 344-400, 1997. (596 refs.)

Many clinicians are confronted by the use of illicit drugs on a daily basis. In dealing with problems related to drugs - opioids, psychostimulants, benzodiazepines, alcohol and nicotine- clinicians need a scientific understanding of their pharmacology, quantifiable effects, and potential adverse effects. Generally, rapid absorption, rapid entry into the central nervous system, high bioavailability, short-half-life, small volume of distribution, and high free drug clearance are pharmacokinetics characteristics which predict a high potential for harmful use, because these factors increase positive reinforcement. Drug users adapt the method and route of administration to optimize delivery of the drug to the brain and to maximize bioavailability. Inhalation and smoking are the routes of administration which allow the most rapid delivery while intravenous injection maximizes the bioavailability. Each route has attendant complication related to mucosal damage, carcinogenesis, and risk of infection. Negative reinforcement or withdrawal is a major drive to recurrent use. Many illicit drugs have pharmacological features that promote dependence, including long, half-life, low free drug clearance and sufficient drug exposure to allow the development of tolerance. The preventive or reductive pharmacotherapies make use of several subsets of agents, those which act on the same receptor or system as the illicit drug (methadone), those which produce an adverse reaction on consumption (disulfiram) and those which symptomatically attenuate illicit drug withdrawal (clonidine). The complications of illicit drug use present many therapeutic challenges. Illicit drug users are prone to developing drug interactions. The most common are pharmacodynamic in nature, most often due to additive effects. However, alcohol, cocaine, disulfiram, methadone, and tricyclic antidepressants may be involved in important pharmacokinetic interactions. Of these the effect of long term alcohol consumption in increasing the hepatotoxicity of paracetamol and of cytochrome P450 3A microsomal stimulating drugs are the most commonly encountered. Charts and tables help summarize the information. [Note. Cannabis is not included because there is not convincing evidence of significant contribution to morbidity and mortality. Similarly the hallucinogens are not covered because they account for little mortality or morbidity.]

Ridout F; Gould S; Nunes C; Hindmarch I. The effects of carbon dioxide in champagne on psychometric performance and blood-alcohol concentration. Alcohol and Alcoholism 38(4): 381-385, 2003. (23 refs.)

Aims: To assess the effects of carbon dioxide (CO2) in champagne on psychomotor performance and blood-alcohol concentration (BAC). Methods: Twelve subjects consumed ethanol (0.6 g/kg body weight) served as champagne or champagne with the CO2 removed, in a crossover study. Results: Champagne produced significantly greater BACs and significantly increased reaction times in a divided attention task, than degassed champagne. Conclusions: The CO2 in champagne may accelerate absorption of alcohol, leading to more rapid or severe intoxication.

Roine R. Interaction of prandial state and beverage concentration on alcohol absorption. Alcoholism: Clinical and Experimental Research 24(4): 411-412, 2000. (7 refs.)

Schwartz JG; Salman UA; McMahan CA; Phillips WT. Gastric emptying of beer in Mexican-Americans compared with non-Hispanic whites. Metabolism: Clinical and Experimental 35(9): 1174-1178, 1996. (33 refs.)

Gastric emptying studies were performed on 11 nondiabetic Mexican-Americans and 11 nondiabetic non-Hispanic whites following ingestion of 450 ml beer. Plasma glucose, serum insulin, and serum alcohol levels were measured in the fasting state and at 7, 15, 30, 45, and 60 minutes following ingestion of the beer. The area under the gastric emptying curve was significantly larger for non-Hispanic whites compared with Mexican-Americans (P=.0492), indicating that Mexican-Americans had faster stomach emptying. Partial correlation coefficients (adjusted for ethnicity, gender, age, and body mass index [BMI]) showed the gastric half-emptying time was inversely related to the incremental levels of glucose (r=-.709, P=.0010) and alcohol (r=-.650, .0035). The faster the rate of gastric emptying of beer, the higher the glucose and alcohol levels. There were no significant correlations between insulin and the rate of gastric emptying. The caloric emptying rate for the beer was much more rapid than previously reported for other liquid meals.

Shoaf SE. Pharmacokinetics of intravenous alcohol: Two compartment, dual Michaelis-Menten elimination. Alcoholism: Clinical and Experimental Research 24(4): 424-425, 2000. (4 refs.)

Swift R. Transdermal alcohol measurement for estimation of blood alcohol concentration. Alcoholism: Clinical and Experimental Research 24(4): 422-423, 2000. (3 refs.)

Thomasson H. Alcohol elimination: Faster in women? Alcoholism: Clinical and Experimental Research 24(4): 419-420, 2000. (11 refs.)

Winek CL; Wahba WW; Dowdell JL. Determination of absorption time of ethanol in social drinkers. Forensic Science International 77(3): 169-177, 1996. (6 refs.)

This study was designed to determine the peak, plateau and absorption times of ethanol in a social drinking setting. For the purpose of this study, subjects who had drinking times of 30 min or greater were considered to fit the 'social drinking' category. Healthy subjects (31 male and two female) were tested immediately after they finished drinking. Blood alcohol concentrations (BACs) were measured using a breath testing instrument (Intoxilyzer(R) 5000). Drinking time, type and volume of alcoholic beverage consumed, subject's weight, and a brief description of the breakfast meal were recorded for each subject. The peak, plateau and absorption times were determined for each subject. Peak time was the time interval between the end of drinking and the maximum blood alcohol measurement. Plateau time was the time interval between peak time and the end of absorption time, i.e. the interval between peak time and the beginning of dissipation. Absorption time was defined as the peak time plus plateau time. Among 31 subjects with drinking times of 30 min or greater, 23 (74.2%) had peak and absorption times of < 30 and < 60 min. respectively. Twenty four out of 31 (77.4%) social drinkers had an absorption time of < 60 min, regardless of their peak time. Overall, the average peak and absorption times were 17.4 +/- 17.3 (range 0-74) and 42.2 +/- 31.5 (range 1-130) min. Plateau times averaged 24.9 +/- 23.1 with a range of 0-74 min. It can be concluded from this study that in a social drinking setting, a shorter time to peak and faster rate of absorption may occur when ethanol is consumed over an extended period of time. This is in contrast to results reported in earlier studies involving bolus drinking, where longer absorption times occurred.

Wright NR; Cameron D. The influence of habitual alcohol intake on breath-alcohol concentrations following prolonged drinking. Alcohol and Alcoholism 33(5): 495-501, 1998. (27 refs.)

Fifty-one healthy men aged 20-35 years kept daily drinking diaries for 4 weeks prior to a 90-min drinking session of 1 ml of ethanol/kg body weight, taken as 4% alcohol by volume lager, at a constant rate, whilst fasting. This was followed by repeat breath-alcohol measurements for 90 min. Habitually light drinkers had significantly lower breath-alcohol levels than heavier drinkers up to 10 min post- drinking. Variation in breath-alcohol level was independent of habitual intake 15-90 min post-drinking. However, habitually light drinkers still had significantly lower blood-alcohol levels than heavy drinkers 30 min post-drinking. Group mean post-drinking breath- alcohol levels peaked at 20 min in light and moderate drinkers, at 10 min in heavy drinkers and at 5 min in very heavy drinkers. Wide individual variation in peak and rate of decline of breath-alcohol levels occurred independently of habitual intake and despite experimental control for factors influential on alcohol kinetics. Algorithms for alcohol intake and breath concentrations have limited application if drinking is prolonged. We suggest that pre-absorptive metabolism and/or delayed absorption of alcohol may contribute to lower breath-alcohol levels in habitually light drinkers for 10 min following alcohol intake under the conditions of this study.

Wu KL; Chaikomin R; Doran S; Jones KL; Horowitz M; Rayner CK. Artificially sweetened versus regular mixers increase gastric emptying and alcohol absorption. American Journal of Medicine 119(9): 802-804, 2006. (14 refs.)

BACKGROUND: Mixed alcoholic drinks are increasingly being consumed in "diet" varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with "regular" versions containing sugar. METHODS: We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage ( 30 g ethanol in 600 mL), made with either "regular" mixer containing sucrose ( total 478 kcal), or "diet" mixer ( 225 kcal). RESULTS: Gastric half-emptying time measured by ultrasound ( mean +/- standard deviation) was less for the "diet" than the "regular" drink ( 21.1 +/- 9.5 vs 36.3 +/- 15.3 minutes, P < .01). Both the peak blood ethanol concentration ( 0.053 +/- 0.006 vs 0.034 +/- 0.008 g%, P < .001) and the area under the blood ethanol concentration curve between 0 and 180 minutes ( 5.2 +/- 0.7 vs 3.2 +/- 0.7 units, P < .001) were greater with the "diet" drink. CONCLUSIONS: Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.

Xu BJ; Zheng YN; Sung CK. Natural medicines for alcoholism treatment: A review. Drug and Alcohol Review 24(6): 525-536, 2005. (113 refs.)

Alcoholism is a serious problem throughout the world. The development of alcoholism remedies have medical, social and economical significance. In view of the pitfalls of psychological dependence and adverse behavioural effects of synthetic drugs, the development of low toxicity and high efficiency medicines derived from natural products exhibits expansive market prospects. Based on these considerations, we summarize briefly folk application of traditional hangover remedies and clinical application of herbal complex and patent medicines for alcoholism treatment. We have reviewed the effects of natural medicines on intake, absorption and metabolism of alcohol, as well as the protective effects on alcohol-induced acute and chronic tissue injury.

Zernig G; Battista HJ. Basic pharmacokinetics of alcohol. IN: Zernig G; Saria A; Kurz M; O'Malley SS, eds. Handbook of Alcoholism. Boca Raton: CRC Press Inc., 2000. pp. 421-423. (11 refs.)

This chapter outlines the absorption of alcohol, the rate and factors which influence rate, maximum blood levels achieved calculated by Widmark's formula, the process of metabolism.