Rate Of Ethanol Elimination Research Articles

Comparison of Ethanol Metabolism in Male and Female Cynomolgus Macaques (Macaca fascicularis)

The physiological consequences of drinking ethanol differ among men and women; however, the biological basis of this gender difference is unknown. Our study characterized sex-related blood ethanol concentration (BEC) 60 min postethanol administration and ethanol elimination rates in male and female monkeys and across the phases of the menstrual cycle. Subjects were male (n = 4) and female (n = 4) cynomolgus monkeys (Macaca fascicularis) with a history of ethanol exposure and maintained at a lean body weight by food restriction. On three separate occasions, each monkey was administered 1.0 g/kg ethanol intragastrically and blood samples (20 microl) were collected every 60 min over a 5-hr period. For females, three phases of the menstrual cycle were determined by the presence of menses and plasma progesterone levels. There was no effect of menstrual cycle on mean 60 min BECs or mean rates of elimination. Mean BECs 60 min after 1.0 g/kg ethanol were: males = 86 mg/dl (+/- 2; n = 4) and females = 82 mg/dl (+/- 5; n = 4). There was no effect of sex on the highest BEC measured, which occurred at the 60 min time point in all subjects. Female monkeys did have faster average rates of ethanol elimination [34 +/- 2 (mg/dl)/hr] compared with males [23 +/- 1 (mg/dl)/hr]. The sex differences in metabolism of ethanol found with the macaque monkey model correlates well with human subject studies and suggests this is an appropriate model to further explore gender differences in response to ethanol.

Ciprofloxacin decreases the rate of ethanol elimination in humans

BACKGROUNDExtrahepatic ethanol metabolism is postulated to take place via microbial oxidation in the colon, mediated by aerobic and facultative anaerobic bacteria.AIMSTo evaluate the role of microbial ethanol oxidation in the...

Ciprofloxacin administration decreases enhanced ethanol elimination in ethanol-fed rats.

Many colonic aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are capable of oxidizing ethanol to acetaldehyde. Accordingly, some ingested ethanol can be metabolized in the colon in vivo via the bacteriocolonic pathway for ethanol oxidation. By diminishing the amount of aerobic colonic bacteria with ciprofloxacin treatment, we recently showed that the bacteriocolonic pathway may contribute up to 9% of total ethanol elimination in naive rats. In the current study we evaluated the role of the bacteriocolonic pathway in enhanced ethanol metabolism following chronic alcohol administration by diminishing the amount of gut aerobic flora by ciprofloxacin treatment. We found that ciprofloxacin treatment totally abolished the enhancement in ethanol elimination rate (EER) caused by chronic alcohol administration and significantly diminished the amount of colonic aerobic bacteria and faecal ADH activity. However, ciprofloxacin treatment had no significant effects on the hepatic microsomal ethanol-oxidizing system, hepatic ADH activity or plasma endotoxin level. Our data suggest that the decrease in the amount of the aerobic colonic bacteria and in faecal ADH activity by ciprofloxacin is primarily responsible for the decrease in the enhanced EER in rats fed alcohol chronically. Extrahepatic ethanol metabolism by gastrointestinal bacteria may therefore contribute significantly to enhanced EER.

Ethanol utilization for metabolite production by Candida utilis strains in liquid medium

AbstractEthanol has been reported to be a gaseous pollutant, originating from the agricultural industry. Interest in its biodegradation has increased over the last two decades. Most of the current studies have focused on its elimination by mixed cultures. This study is part of a broader project intended to utilize Candida utilis strains for gaseous ethanol elimination and to eventually bioconvert them into biomass and/or volatile metabolites. We present here the study of six strains (one from the ATCC and five from the ICIDCA collection) cultivated in a liquid medium, with initial ethanol concentrations of 16 g/l and 32 g/l. At 16 g/l, a maximum ethanol elimination rate of 0.13 g/l × h was obtained in four of the six strains (ATCC 9950, L/375–1, L/375–5 and L/375–10). This rate increased to 0.21 g/l × h with an initial ethanol concentration of 32 g/l. The L/375–5 strain was the best biomass producer (3.3 g/l) at 32 g/l, while the highest ethyl acetate production (0.80 g/l) was obtained with the L/375–1 strain. The L/375–25 and L/375–26 strains which showed very low ethyl acetate production were, by way of contrast, efficient acetaldehyde producers, with 0.54 g/l and 0.66 g/l measured in the broth. While biomass production reached its maximum after two days of culture, the production of acetic acid and ethyl acetate continued during the third day. The results for biomass and metabolite production obtained with the ICIDCA collection strains (L/375–1, L/375–5 and L/375–10) were better than those obtained with the ATCC 9950 strain, although the latter often has been reported to be particularly suitable for metabolite production.

Use of a Two‐Compartment Model to Assess the Pharmacokinetics of Human Ethanol Metabolism

The relationship between blood ethanol concentration and hepatic ethanol metabolism commonly is calculated using the Michaelis-Menten equation and a one-compartment model that assumes equality of blood and hepatic ethanol concentrations. However, at low blood concentrations, most of the ethanol arriving at the liver is metabolized, and hepatic ethanol concentrations may fall far below that of the entering blood. We have developed a two-compartment model of ethanol metabolism that accounts for the fall in ethanol concentration that may occur as blood traverses the liver and used this model to make predictions concerning ethanol metabolism at various blood ethanol concentrations. The two-compartment model predicts that near-complete saturation will occur more abruptly and at a lower blood concentration (approximately 3 mM) than is the case with the one-compartment model. Thus, the two-compartment model predicts a near-constant ethanol elimination rate for blood ethanol concentrations above 3 mM (as commonly observed in human subjects), whereas the one-compartment model predicts an increasing elimination rate over the range of concentrations observed in experimental studies. In agreement with observed data, the two-compartment model predicts that first-pass metabolism should be extremely sensitive to the rate of ethanol absorption. Application of this model to previously published data indicated that, when absorption was slowed via concomitant food ingestion, first-pass metabolism accounts for approximately 50% and 10% of ethanol dosages of 0.15 g/kg and 0.3 g/kg, respectively. When ingested without food, there is negligible first-pass metabolism of even very small ethanol dosages (0.15 g/kg). These findings suggest that first-pass metabolism is an unimportant determinant of the blood ethanol response to ingestion of potentially inebriating doses of ethanol.

High blood endotoxin does not affect ethanol elimination in rats.

Gut-derived endotoxins have been proposed as mediators of the enhancement of ethanol elimination after chronic alcohol administration. We investigated whether chronically elevated blood-endotoxin levels affect the rate of ethanol elimination in a study where endotoxin was administered chronically from an osmotic minipump to rats fed ethanol in a liquid diet. As expected, an acute dose of ethanol (1.2 g/kg body wt, i.p.) was eliminated significantly faster (329+/-11 mg/kg/h) by chronically ethanol-fed animals than by pair-fed controls (285+/-9 mg/kg/h). However, although endotoxin administration significantly elevated blood-endotoxin levels, the rate of ethanol elimination in endotoxin-treated groups was almost identical when compared either to controls (289 vs 285) or to ethanol-fed rats (328 vs 329). We conclude that chronic endotoxin exposure at levels that only resulted in mild hepatic changes, had no effect on the rate of ethanol elimination and that it is unlikely that endotoxins are involved in the induction of the ethanol elimination rate following chronic alcohol administration.

Decreased activity of gastric class III (χ) ADH can explain increased bioavailability of alcohol in women

Women are more vulnerable than men to alcohol-induced diseases. This could be due to their higher blood levels. No comparable effect was observed after i.v. administration, suggesting an increased bioavailability of the imbibed alcohol. Furthermore, below the age of 50, this effect was associated with a decrease in total gastric ADH activity, rather than with a lesser rate of ethanol elimination, which in fact may be increased in women. To quantify the difference in bioavailability, the amount of alcohol that reaches the systemic blood after i.v. and oral administration of the same dose (0.3 g/kg body wt.) was compared one hour after a standard meal in 20 men and 17 women. This amount (first-pass metabolism; FPM) was estimated by the differences in areas under the i.v. and oral blood alcohol curves and quantified by integration of the Michaelis-Menten equation over the entire curve of blood concentrations. In women, FPM was 10% of the dose, compared to 21% in men (p < 0.01). It correlated with total gastric ADH activity at 500 mM of ethanol, a concentration likely to occur in the stomach. The gastric mucosa expresses the following 3 classes of ADH isozymes in a decreasing order of affinity for ethanol: ~tADH, a Class I isozyme also present in the liver, zADH, a Class IV ADH characteristic of the upper gastro-intestinal tract, and ~ADH, a Class III isozyme found in most tissues. All of them can operate at the high alcohol concentrations prevailing in the stomach after the drinking of alcoholic beverages. To investigate which isozyme was involved in the gender difference, we used endoscopic biopsy tissue obtained from the gastric corpus of 30 men and 19 women, with normal histology and no H. pylori infection. Activity of the ADH isozymes was assesed by using preferred substrates for Class I (acetaldehyde) and Class IV (m-nitrobenzaldehyde) and a specific reaction of Class III, namely glutathione-dependent formaldehyde dehydrogenase. Since we previously observed an increased bioavailability of imbibed alcohol in Japanese subjects (compared to Caucasians) in association with decreased zADH activity, we focused on this Class IV isozyme. Unexpectedly, there was only a trend for a decrease in Class IV activity in women, with no differences in Class I ADH activity, but there was a 58% reduction in Class III ADH, determined by the formaldehyde dehydrogenase activity (p < 0.003). In summary, 1) an increased bioavailability of imbibed alcohol in women compared to men was confirmed and quantified, 2) this was found to be associated with, and probably due to, a reduced gastric Class III (Z) ADH activity of women compared to men. Since )~ADH is present in most tissues, the significance of a possible decrease in its physiological activity with other substrates is now being explored in various tissues, including the liver.

Ciprofloxacin medication decreases ethanol elimination rate in man

Ciprofloxacin medication decreases ethanol elimination rate in man

Pharmacokinetics of ethanol in patients with renal failure before and after hemodialysis

We studied the pharmacokinetics of ethanol in seven patients suffering from terminal renal failure before and after they underwent hemodialysis. Ethanol (0.40 g/kg) was administered in the morning after an overnight fast by a constant rate intravenous (IV) infusion over 45 min. After removing a mean fluid volume of 2.46±0.48 liters (±SD), span 1.76–3.43 liters by hemodialysis, the same subjects received a second IV infusion of ethanol after they had eaten lunch. At exactly timed intervals of 0, 45, 90, 105, 120, 135, 150, 165, and 180 min from the start of the infusion, two blood-samples were drawn and the plasma portion of one of them was obtained by centrifugation. The concentration of ethanol in blood and plasma was determined by headspace gas chromatography and the water-content of whole blood was determined from the change in weight after desiccation. Plasma always contained a higher concentration of ethanol than whole blood and the mean plasma/whole blood ratio in patients with renal failure was 1.07:1 (span 1.05–1.10). The rate of ethanol disappearance from blood ( β-slope) was faster (0.185±0.013 versus 0.157±0.022 g/l/h), the C 0 value was higher (0.79±0.08 versus 0.73±0.10 g/l) and the apparent volume of distribution ( V d) of ethanol was lower (0.507±0.049 versus 0.558±0.078 l/kg) after hemodialysis. The water content of whole blood was significantly higher ( P<0.001) before dialysis (88.6±1.97 g/100 ml) compared with after dialysis (87.4±2.01 g/100 ml). The higher V d for ethanol and lower C 0 as well as higher blood-water content are to be expected for a over hydrated condition before hemodialysis. The swifter rate of ethanol elimination from blood ( β-slope) after hemodialysis should be interpreted with caution because eating a meal before the second infusion of ethanol is a confounding factor. Nevertheless, the rate of elimination of ethanol from blood in patients with renal failure agreed reasonably well with values expected for healthy subjects, namely mean 0.15 g/l/h spanning from 0.10 to 0.20 g/l/h.

The kinetics of methanol elimination in alcoholics and the influence of ethanol

Methanol concentrations were studied during the end phase of ethanol elimination and for about five hours afterwards in 12 alcoholics admitted with alcohol intoxication for acute care. The rate of ethanol elimination ( β 60) ranged from 0.114 g/kg/h to 0.270 g/kg/h (mean 0.178±0.045 g/kg/h). The methanol concentration was found to remain almost steady as long as ethanol levels were relatively high, and changed only to an extent that could be explained by the combined opposing influences of methanol excretion and endogenous synthesis. There was no significant relationship between the rate of ethanol elimination and the methanol level. The methanol concentration began to decrease when the ethanol concentration had fallen to under 0.2 g/kg. When the ethanol concentration had fallen to base levels, methanol was eliminated at a rate characterized by an elimination constant ( k el) of 0.212–0.481 h −1, and a half life of 1.44–3.27 h. There was a positive correlation between the rate of ethanol elimination and the rate of methanol elimination ( r=0.642; p<0.05).

INHIBITION OF BACTERIOCOLONIC PATHWAY FOR ETHANOL OXIDATION BY CIPROFLOXACIN IN RATS

Many colonic bacteria possess marked alcohol dehydrogenase (ADH) activity and are capable of oxidizing ethanol to acetaldehyde both in vitro and in vivo. We have recently shown that part of ingested ethanol is metabolized to acetaldehyde in the colon during normal alcohol metabolism. To assess the contribution of this bacteriocolonic pathway for ethanol oxidation to total ethanol metabolism, the elimination rate of ethanol, faecal aerobic flora and faecal ADH activity were determined in rats before and after the treatment with ciprofloxacin (200mg/kg/day) for four days. Ciproflaxacin treatment decreased ethanol elimination rate from 310±9 to 282±13 mg/kg/h (mean±SE; p<0.02), markedly reduced faecal aerobic flora, and also lowered faecal ADH activity from 63±17 to 17±7 nmol/min/mg faeces (p<0.05). Neither hepatic ADH nor microsomal ethanol oxidizing system activities were affected by the ciprofloxacin treatment. On the contrary, an acute intraperitoneal dose of ciprofloxacin had no effect on the rate of ethanol elimination. These results support the significant role of the bacteriocolonic pathway in total ethanol elimination, and open a new, microbiological, perspective for studies on ethanol metabolism and pathogenesis of alcohol related organ damages.

Female rats exhibit greater susceptibility to early alcohol-induced liver injury than males

It is known that women develop hepatic injury more rapidly and with exposure to less ethanol than men; however, mechanisms remain unclear. The purpose of this study was to determine if an enteral alcohol delivery model could be used to study susceptibility of females to alcohol-induced liver injury. Male and female Wistar rats (age- or weight-matched) were given ethanol (11-12 g.kg-1.day-1) continuously for up to 4 wk via intragastric feeding, and control rats received a high-fat diet without ethanol. There were no significant differences in body weight among the groups studied. Furthermore, mean ethanol concentrations, their cyclic pattern in urine, and rates of ethanol elimination were also not different between the genders under these conditions. Ethanol treatment elevated serum aspartate aminotransferase levels in male rats to 126 +/- 10 IU/l after 4 wk. In females, however, values increased more rapidly and reached significantly higher values at 4 wk (168 +/- 18 IU/l). Steatosis, inflammation, and necrosis assessed histologically also developed more rapidly and were more severe in females than males. Steatosis due to ethanol exposure, which was localized in centrilobular areas in males, was panlobular in the female. Moreover, endotoxin in plasma, intercellular adhesion molecule 1 expression in hepatic sinusoidal-lining cells, and the number of infiltrating inflammatory cells in the liver were 2-2.5-fold greater in females than males. These changes possibly account for increased hepatic injury due to ethanol in the female.

Methanol elimination in non-alcoholics: inter- and intraindividual variation

Five male subjects aged between 25 and 40 years were given methanol at a dose of 10 mg/kg, once orally and once intravenously, while the enzyme systems responsible for methanol oxidation were blocked by ethanol. The study assessed the duration of inhibition of methanol oxidation in relation to the blood ethanol concentration, and the elimination of methanol not influenced by ethanol. Methanol elimination was found to begin at a blood ethanol concentration of 0.04–0.13 g/kg. Elimination constants of 0.406–0.267 h −1 with corresponding half-lives of 1.71–2.60 h were established for methanol not influenced by ethanol. When data from a previous study using an identical protocol for parenteral administration were included, making the total number of subjects nine, the mean elimination constant was found to be 0.298±0.470 h −1 and the mean half-life 2.37±0.357 h, distribution being normal. No evidence of any differences in methanol elimination kinetics between alcoholics and non-alcoholics or of a significant influence of the route of administration was found. The extent of intraindividual variation in methanol elimination, as indicated by the difference in each subject between the values established, expressed as a percentage of the corresponding mean values, was found to be 3–25%, which is comparable to the magnitude of intraindividual variation in the rate of ethanol elimination.

The Effect of Cimetidine on Ethanol Concentrations in Fasting Women and Men after Two Different Doses of Alcohol

Background: Serum ethanol concentrations may become higher when alcohol is consumed during treatment with histamine receptor antagonists, especially if ethanol is ingested postprandially. Only a few studies have investigated fasting subjects, and women have only been investigated sporadically. Methods: The present study compared serum ethanol concentrations after a 4-h fast followed by a low (0.15 g/kg) and a high (0.45 g/kg) dose of ethanol, on two separate occasions in six women and six men. The study was carried out before and after treatment with 400 mg cimetidine twice daily. Results: Cimetidine administration did not change the area under the concentration-time curve or the maximal serum ethanol concentration in either women or men, irrespective of ethanol dose. Ethanol elimination rate was unchanged by cimetidine. Conclusion: Cimetidine does not influence the ethanol concentration-time curve when ethanol is ingested on an empty stomach.

Noncompetitive‐Like Inhibition of Ethanol Elimination by Cyanamide Treatment: Pharmacokinetic Study

The effect of acetaldehyde accumulation of ethanol elimination is of interest in medico-legal practice in Japan. We examined the pharmacokinetic mechanism of the inhibition of ethanol metabolism by cyanamide, an inhibitor of mitochondrial aldehyde dehydrogenase. An ethanol solution (0.25-2.0 g/kg body weight) was injected intravenously into male rabbits with or without administration of cyanamide. Cyanamide was injected intraperitoneally (25 mg/kg body weight) to the cyanamide-treated group 2 hr before ethanol injection. Blood ethanol and acetaldehyde concentrations were measured periodically by head-space gas chromatography. The MULTI(RUNGE) computer program was applied for the pharmacokinetic analysis. One- or two-compartment open models with Michaelis-Menten elimination kinetics were used for simultaneous multi-line fitting. The ethanol elimination rate decreased by cyanamide treatment. The border-point concentration between pseudolinear and curvilinear phases was not affected by cyanamide treatment. The estimated Vmax value decreased by cyanamide treatment, whereas the K(m) value did not change. Our results correspond to a noncompetitive-like inhibition of ethanol metabolism. K(m) is related to the border point between pseudolinear and curvilinear phases. Thus, our findings in the blood ethanol concentration-time curve suggest adequate curve-fitting. The product, or competitive, inhibition of alcohol dehydrogenase by acetaldehyde had been reported in enzymological study. The pharmacokinetic manner of inhibition in vivo was different from the enzymologic mechanism in vitro. Other metabolic factors related to ethanol metabolism are thought to be more important than acetaldehyde accumulation itself.

Effect of the Cytochrome P‐1450IIE1 Genotype on Ethanol Elimination Rate in Alcoholics and Control Subjects

We studied an influence of genetic polymorphisms in the cytochrome P-450IIE1 (CYP2E1) gene on ethanol elimination rate in alcoholic patients and healthy subjects. The CYP2E1 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method for 124 alcoholics and 54 healthy subjects. There was no significant difference in the gene frequency of CYP2E1 between alcoholics and healthy control subjects. Blood ethanol concentrations in the 65 alcoholics on admission ranged from 0.32 to 4.22 mg/ml. In the patients with the c1/c2 genotype, the elimination rate was significantly correlated with blood ethanol concentration. In each of the three genotypes of CYP2E1, the patients were divided into three groups based on ethanol concentrations. The average of the ethanol elimination rate in the patients with c1/c2 having blood ethanol levels of > or = 2.5 mg/ml was significantly higher than the rates in the two other groups of c1/c2. When blood ethanol levels were > or = 2.5 mg/ml, the elimination rate in the patients with c1/c2 was significantly higher than that in those with c1/c1. Regardless of the CYP2E1 genotype, the elimination rate in the alcoholics was higher than that in the control subjects when blood ethanol levels were < 1.0 mg/ml. These results suggest the possibility that the c2 allele of CYP2E1 Influences the rate of ethanol elimination at high ethanol levels. The rate of ethanol elimination was independent of liver disorder judged by serum total bilirubin values.

Problems in pharmacokinetic analysis of alcohol disposition: a trial of the Bayesian least-squares method.

The technical problems of the pharmacokinetic analysis of alcohol disposition were studied using the Michaelis-Menten elimination kinetic model. This model was defined by two forms of equations: differential and integrated, with the latter being derived by integration of the differential equation. We compared the parameter values, estimated by one-line curve-fitting, using these two equation forms. We concluded that, for the kinetic analysis of alcohol disposition, curve-fitting with the differential equation was superior to that with the integrated equation. We also studied the methodological problems involved in one-line fitting. The ordinary least-squares (OLS) method was compared with the Bayesian least-squares (BLS) method. Correlation between the Vmax and beta (ethanol elimination rate) values, and between the Vmax and K(m) values was seen when the parameter values were estimated by the OLS method. These results suggested that one-line fitting by the OLS method was not adequate for Michaelis-Menten-type elimination kinetic analysis. BLS analysis resulted in no correlation between the estimated parameter values that did not change with the level of the dose. The BLS method seemed to be more useful than the OLS method for the estimation of individual pharmacokinetic parameter values.

ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics.

The class I hepatic alcohol dehydrogenases (ADHs) are primarily responsible for ethanol metabolism in humans. Genetic polymorphism at the ADH2 locus results in the inheritance of isozymes of strikingly different catalytic properties. The most common ADH2 allele, ADH2*1, encodes the low K(m) isozyme subunit beta 1. The ADH2*3 allele encodes a high-activity isozyme subunit of alcohol dehydrogenase, beta 3, identified in approximately 25% of African-Americans. The Vmax of beta 3 beta 3-ADH is 30 times greater than that of the beta 1 beta 1-ADH. Therefore, we hypothesized that the rate of ethanol metabolism, an important factor in the toxicity of ethanol, in persons with beta 3-containing ADH, either beta 3 beta 3- or beta 1 beta 3-ADH, would be faster than that of persons with only beta 1 beta 1-ADH. We tested this hypothesis with ethanol administered orally to healthy, young African-Americans. Three hundred and twenty-six African-American men and women were genotyped using polymerase chain reaction amplification of their leukocyte DNA followed by hybridization with allele-specific probes. One hundred twelve volunteers, selected by genotype, received an oral dose of ethanol designed to produce a blood ethanol concentration of 80 mg/dl (0.080 g/dl), when the blood alcohol concentration-time curve was extrapolated back to time 0. Ethanol metabolic rates (beta 60s) were determined in the 112 subjects from the slope of the pseudolinear portion of the blood ethanol concentration-time curves. The mean beta 60 of African-Americans having beta 3-containing ADH isozymes had significantly faster ethanol elimination rates than those with only beta 1 beta 1-ADH isozymes. There were no significant differences in body weight, ethanol intake in the week before testing, peak breath ethanol concentration, time to peak, or volume of distribution between the genotype groups. Within each of these groups, men had lower ethanol disappearance rates than women. These results demonstrate in vivo the kinetic differences of ADH2 isozymes that may influence individual risk for the effects of ethanol.

Severe ethanol intoxication in an adolescent

A 15-year-old boy presented to the emergency department with status epilepticus and a blood ethanol concentration of 757 mg/dL. Mechanical ventilation and substantial amounts of benzodiazepines were required. His hospital course was complicated by aspiration pneumonia, but he had no episodes of hypoglycemia. He received 2.8 hours of hemodialysis, which increased the rate of ethanol elimination, but there is no evidence that hemodialysis improved his clinical outcome. To our knowledge, this is the highest blood ethanol level reported in a child or adolescent who survived.

Ethanol elimination rates in an ED population.

Knowledge of the rate of ethanol elimination is essential in the assessment of the intoxicated patient. Surprisingly little literature is available regarding ethanol elimination rates in emergency department (ED) patients; prior studies almost exclusively examined populations of alcoholics or normal controls. Consequently, this prospective observational study was undertaken to assess the rate of ethanol elimination in an ED population. Twenty-four consecutive adult ED patients clinically suspected of intoxication who had serum ethanol determinations drawn were enrolled. Patients underwent serial ethanol determinations via breathalyzer (Intoxilyzer 1400, CMI Inc., Owensboro, KY). Linear regression analysis of the plot of decrease in ethanol level over time was performed to determine the rate of ethanol elimination. Initial ethanol levels in the 24 patients ranged from 58 to 447 mg/dL (mean, 249 +/- 109 [SD] mg/dL). Patients were observed for a minimum of 2 and a maximum of 9 observations (mean, 3.9 +/- 1.7), over a period of 0.5 to 12.1 hours (mean, 4.4 +/-3.5 h). Clinical features of intoxication were poorly correlated with ethanol level (r < .5). The rate of ethanol elimination in the ED population was 19.6 mg/dL/h (r = .83; 95% confidence interval [CI], 16.9 to 22.3 mg/dL/h). Subgroup analysis found differences that were statistically significant but small. Multiple regression analysis showed that time was the major variable useful in predicting changes in ethanol level (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)