Rate Of Ethanol Elimination Research Articles

The Effect of Ibuprofen on Ethanol Concentration and Elimination Rate

Pursuant to a recent driving under the influence (DUI) case, a medical study of six subjects was cited reporting that ibuprofen causes a decrease in the maximum rate of elimination of ethanol. Such a drug interaction is of significant forensic science interest and warrants further examination. This study investigates the effect of ibuprofen on ethanol elimination rate and ethanol concentration in nineteen volunteers. Volunteer subjects were randomly assigned to two groups administered either a placebo followed by ethanol or ibuprofen followed by ethanol. Subjects served as their own control. Blood ethanol concentrations were monitored every 30 to 60 min for up to 4 h with Intoximeter 3000 instruments. A blood sample was drawn at the final Intoximeter test and analyzed for ethanol and ibuprofen by gas chromatography and mass spectrometry, respectively. The mean elimination rate (+/- SD) as calculated using Widmark's elimination factor was 0.018 +/- 0.006 g/dL for ethanol and 0.017 +/- 0.007 g/dL/h for ethanol with ibuprofen. Mean ethanol concentrations (g/dL +/- SD) were: 0.095 +/- 0.026 (ethanol) and 0.095 +/- 0.033 (ethanol and ibuprofen) at 30 min; 0.077 +/- 0.026 (ethanol) and 0.075 +/- 0.031 (ethanol and ibuprofen) at 150 min; and 0.089 +/- 0.025 (ethanol) and 0.087 +/- 0.030 (ethanol and ibuprofen) overall. There was no statistically significant affect of ibuprofen on either the peak blood ethanol concentration or the ethanol elimination rate (p less than or equal to 0.001). These results reveal no evidence of a significant ethanol-ibuprofen interaction.

Chronic ethanol consumption produces genotype-dependent tolerance to ethanol in LS/Ibg and SS/Ibg mice

It is well known that chronic ethanol administration produces tolerance to the sedative-hypnotic and hypothermic effects as well as low-dose locomotor inhibitory effects of ethanol. We report herein characterization of a convenient method of producing genotype-dependent functional tolerance to ethanol-induced locomotor inhibition. Mice, LS/Ibg (LS) and SS/Ibg (SS), which differ markedly in acute effects of ethanol on locomotor activity, hypothermia, and hypnotic sensitivity, were required to consume solutions of ethanol in water as the sole source of liquid. Mice were provided lab chow ad lib. and the following regimen of ethanol in water, v/v: 10% for 4 days, 15% for 7 days, 20% for 7 days, followed by 15% for periods longer than 2 weeks. Control animals received water only or were pair-fed sucrose (isocaloric with ethanol) solutions plus lab chow; both control and ethanol-consuming (15 g ethanol/kg/24 h) mice maintained similar body weights for up to 4 weeks. Blood ethanol concentrations from 10–200 mg% were obtained during a 12 L:12 D cycle. At 6 h following withdrawal, LS and SS mice showed differential dose-dependent tolerance to locomotor inhibitory effects of ethanol. However, low-dose locomotor activation was unaltered in either line of mice, and results indicate that an apparent sensitization in SS mice is secondary to development of tolerance to locomotor inhibition. Maximum tolerance to locomotor inhibition was observed after 2 weeks of chronic ethanol consumption, with responses returning to control values within 1–2 weeks after withdrawal. Rates of acquisition of tolerance were similar in LS and SS mice. LS but not SS mice developed tolerance to ethanol-induced hypothermia, but neither line acquired tolerance to the hypnotic effects of ethanol. While LS mice acquired some metabolic tolerance, tolerance to locomotor inhibition or hypothermia was not mediated by alterations in ethanol elimination rates indicating marked neuroadaptation, that is, changes in CNS sensitivity. Only slight hypothermia and zero scores for handling-induced seizures were observed after withdrawal from 2–4 weeks of chronic ethanol intake. The results indicate that different genotype-dependent mechanisms may mediate or modulate hypnotic effects and activating or inhibitory effects of subhypnotic doses of ethanol and that these processes respond differentially to chronic ethanol intake. It is proposed that this ethanol intake model will be valuable in examining neurochemical processes hypothesized to mediate neuroadaptation to locomotor inhibitory effects of ethanol.

Interaction of aging and lifelong ethanol ingestion on ethanol-related behaviors and longevity

The interactions of aging and long-term voluntary ethanol consumption were studied in the alcohol-preferring AA (Alko Alcohol) rats. The mean daily ethanol intake was 6.45 ± 0.31 g/kg/dy (mean ± SE at the beginning of the exposure at 3 months of age. The control animals were given only food and water ad libitum. There was no difference in survival or weight gain between the control and ethanol groups. When tested for voluntary ethanol intake at the age of 24 months, the rats in the ethanol group consumed significantly more ethanol than the controls. The two groups did not differ in ethanol-induced motor impairment, sleep-time, or hypothermia, nor in the rate of ethanol elimination. The 24-month-old animals, however, showed higher sensitivity to ethanol than the 3–4-month-old rats in the sleep-time test. It is concluded that the feeding regimen used in this study did not produce any detecaable intetactions between ethanol and the aging processes in the AA rats.

Inhibition of ethanol metabolism by fructose in alcohol dehydrogenase-deficient deer mice in vivo

The purpose of this work was to compare the roles of a newly described mitochondrial dehydrogenase and catalase in ethanol elimination in deer mice deficient in alcohol dehydrogenase (ADH −). Fructose was used because of its well-known ability to stimulate dehydrogenase-dependent ethanol metabolism. Rates of ethanol metabolism in vivo were decreased significantly by about 60% in a dose-dependent manner by fructose in deer mice fed an ethanol-containing or a corn oil control diet. In addition, rates of metabolism of methanol, a selective substrate for catalase in rodents, were similar to rates of ethanol elimination and were decreased from 6.9 ± 1.0 to 1.7 ± 0.5 mmol/kg/h by fructose, supporting the hypothesis that catalase and not a mitochondrial dehydrogenase predominates in ethanol oxidation in ADH − deer mice. Glycolate, a substrate for peroxisomal H 2O 2 generation, reversed the inhibition of alcohol metabolism by fructose completely, indicating that fructose did not inhibit catalase directly. As expected, the ATP ADP ratio was decreased by fructose significantly from 4.2 ± 0.4 to 2.4 ± 0.4 in deer mouse livers. These data are consistent with the hypothesis that fructose decreases catalasedependent ethanol metabolism in vivo by inhibiting hepatic H 2O 2 generation.

Effect of Dihydrotestosterone on the Rate of Ethanol Elimination in Healthy Men

Testosterone (T) and, more potently, dihydrotestosterone (DHT), are in vitro inhibitors of hepatic alcohol dehydrogenase (ADH). An increase in the rate of ethanol disappearance (RED) in man has been observed after orchidectomy. We thus investigated the influence of DHT administration on RED in 10 healthy male volunteers. RED was estimated after an oral ethanol bolus (0.6 g/kg), before and after a 14-day treatment with DHT (2 x 125 mg per day percutaneously; Andractim, Besins iscovesco, France). A mean 11.5-fold increase in DHT levels and a 2.0-fold decrease in T values were observed after DHT administration, confirming the good compliance with treatment. RED was decreased after DHT (0.168 +/- 0.043 vs. 0.137 +/- 0.043 g/l/hr; mean +/- SD; p less than 0.01 using Wilcoxon's paired comparison test). These data are consistent with a DHT-induced inhibition of hepatic ADH in vivo. This could have a beneficial effect by decreasing acetaldehyde production in alcoholic patients, in whom marked hypoandrogenism frequently occurs.

Purinergic modulation of ethanol-induced sleep time in long-sleep and short-sleep mice

The long-sleep (LS) and short-sleep (SS) mice were selectively bred for differences in sensitivity to the depressant effects of ethanol. In addition to their differential sensitivity to ethanol, they are also differentially sensitive to purinergic agonists and antagonists. This suggests that there may be differences in the purinergic systems of these lines of mice which may aid in understanding how they differ in ethanol sensitivity. We have investigated whether these drugs are capable of modifying acute ethanol sensitivity as measured by ethanol-induced loss of the righting response (ethanol sleep time), waking blood and brain ethanol concentrations, and blood ethanol elimination rate. The purinergic agonists cyclohexyladenosine (CHA), L-phenylisopropyladenosine (PIA), 2-chloroadenosine (CAD), and N-ethylcarboxamidoadenosine (NEC) increased sleep time in both LS and SS mice, however, LS mice were generally more affected than SS. The LS and SS mice were also differentially sensitive to the purinergic antagonists, theophylline and caffeine. Blood and brain ethanol concentration on awakening suggested that CNS sensitivity to acute ethanol administration was altered by pretreatment with agonists but not antagonists. Two agonists, CHA and NEC, significantly lowered ethanol elimination in both lines of mice while PIA, CAD, and the antagonists theophylline, and caffeine were without affect on elimination rate. These data support previous observations that adenosine-mediated systems may be involved in the modulation of ethanol sensitivity.

A New Approach to the Determination of Ethanol Elimination RateIn Vivo:An Extension of Widmark's Equation

In order to provide more experimental data about a single ethanol elimination sequence, tracer amounts of 14C-labelled ethanol were given intravenously in fed and fasted rats into a preexisting pool of unlabelled ethanol. The profiles of the elimination curves of 14C-labelled ethanol were distinctly different from those of unlabelled ethanol. This necessitated the elaboration of a mathematical model based on a two-compartment system, which by using the early distribution phase of the 14C-labelled ethanol and the linear part of the elimination curve of unlabelled ethanol enables the determination of the time-rate constants for distribution of ethanol, K12 and K21 and ethanol elimination rate Q. It is shown that the ratio K21'/(K21' + K12') is "r", the distribution volume of ethanol in the sense of Widmark, K12' is K12 divided with Va (initial distribution space of ethanol) and K21' is K21 divided with Vb (the peripheral compartment). The mean value +/- S.E.M. is 0.57 +/- 0.05 for fed rats and 0.49 +/- 0.03 for fasted. The slope of the time-concentration curve of ethanol, Widmark's beta, is shown to be K12'/(K12' x K21') x Q where Q is ethanol elimination rate. The mean elimination rate is 0.303 +/- 0.036 mmol x l-1 x min-1 in fed rats and 0.219 +/- 0.015 mmol x l-1 x min.-1 in fasted (P less than 0.05). It is concluded that we are now able to extend Widmark's equation by an independent determination of the distribution factor "r".

Evaluation of Blood-Ethanol Profiles after Consumption of Alcohol Together with a Large Meal

ABSTRACTSixteen healthy men drank 1.43 g ethanol per kg of body weight as Swedish aquavit, export beer, and cognac during 90 min together with a 3-course meal. Capillary (fingertip) blood was drawn on 8 occasions starting at 0–10 min after the end of drinking and blood alcohol concentration (BAC) was determined by an enzymatic method. The peak BAC ranged from 0.97–1.41 mg/ml (mean 1.20 mg/ml) and this occurred 78 min after the end of drinking (range 0–230 min). The mean rate of disappearance of alcohol from blood (β) was 0.16 mg/ml/h (range 0.13–0.21) and the apparent volume of distribution of ethanol was 0.795 l/kg (range 0.64–0.93). The mean rate of ethanol elimination from the body was 128 mg/kg/h (range 99–160). The BAC increased on the average by 0.17 mg/ml (range 0.0–0.45 mg/ml) before reaching the maximum level. During the absorption phase, the BAC had attained on the average 83%, 91%, 95% and 98% of the final peak BAC within 5 min, 45 min, 109 min and 175 min, respectively, after ingestion. These ...

Effect of epinephrine on ethanol metabolism by isolated rat hepatocytes

The effect of epinephrine on ethanol metabolism was determined in isolated rat hepatocytes. Epinephrine (10 μM) enhanced an initial rapid rate of ethanol elimination observed in the first 5 min. Thereafter, between 5 and 90 min, the rate of ethanol elimination was slower and not affected by epinephrine. Epinephrine resulted in higher acetaldehyde concentrations at 2 min, but not thereafter. Acetaldehyde production in the presence and absence of epinephrine was inhibited by 4-methylpyrazole, by a low free extracellular calcium concentration, and by the α 1-adrenergic blocker prazosin. Ethanol alone and epinephrine alone increased oxygen consumption, but the effects were not additive. The ethanol-induced decreases in the cytosolic NAD +/NADH and NADP +/NADPH ratios and in the mitochondrial NAD +/NADH ratio were delayed by the presence of epinephrine. An accelerated initial alcohol dehydrogenase activity sufficient to account for the rapid initial rate of ethanol elimination shown with epinephrine was demonstrated by coupling ethanol oxidation with lactaldehyde reduction, a system which increases the rate of dissociation of NADH from the enzyme and its oxidation back to NAD +. The findings in this study indicate that an increased reoxidation of NADH during ethanol oxidation by alcohol dehydrogenase is the basis for the rapid transient increase in ethanol elimination produced by epinephrine.

THE EFFECT OF GLUCOCORTICOIDS, BETA-2-ADRENOCEPTOR AGONISTS, THEOPHYLLINE AND PROPRANOLOL ON THE RATE OF ETHANOL ELIMINATION AND BLOOD ACETATE CONCENTRATION IN HUMANS

The effects of a single dose and of prolonged administration of glucocorticoids and of a single dose of salbutamol, theophylline or propranolol on the rate of ethanol elimination and blood acetate concentration were examined in healthy male students. Mean ethanol elimination rate and mean blood acetate concentration were increased significantly after acute intake of glucocorticoids. After chronic administration of glucocorticoids, the rate of ethanol elimination was significantly increased, whereas blood acetate concentration showed a tendency to increase, but did not reach statistical significance. Changes were found neither in ethanol elimination rates nor in blood acetate levels after single doses of salbutamol, theophylline and propranolol.

Body temperature and ethanol pharmacokinetics in temperature-challenged mice

The relationships between ambient temperature, body temperature, ethanol pharmacokinetics and behavioral sensitivity to ethanol were examined in C57BL/6 mice. Mice were injected intraperitoneally with 3.6 or 2.0 g/kg ethanol. Exposure to increasing ambient temperatures of 4–34°C immediately after ethanol injection resulted in a significant increase in body temperature, ethanol elimination rate and brain:blood ethanol concentration ratios in 3.6 g/kg ethanol-injected mice, but not in mice injected with 2.0 g/kg ethanol. As the mean body temperature increased from 26.0 to 38.2°C in the 3.6 g/kg mice, there was a 50% increase in ethanol elimination rate. Delayed (30 min) exposure to increasing ambient temperatures following injection of 3.6 g/kg ethanol resulted in a significant increase in ethanol elimination rate, a marked increase in the duration of loss of righting reflex and a decrease in ethanol concentration at the regain of righting reflex. The results indicate that temperature-induced changes in the absorption, distribution and elimination of ethanol do not appear to mediate the effects of temperature on behavioral sensitivity to ethanol in C57 mice.

Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference

The effect of naloxone on voluntary ethanol intake was examined in rats which were selectively bred for oral ethanol preference (High Alcohol Drinking or HAD line). Rats of the HAD line were treated with naloxone in doses of 0.05–18.0 mg/kg b.wt. before access to water alone or to a free-choice between a 10% (v/v) ethanol solution and water. Naloxone suppressed water intake when water was presented as the sole source of fluid. In contrast, naloxone produced a dose-dependent decrease in ethanol consumption, without altering water intake, when rats were given a free-choice between the ethanol solution and water. Selective suppression of ethanol consumption by naloxone was not attributable to changes in blood ethanol concentrations or ethanol elimination rates following naloxone treatment. It appears that although naloxone may attenuate the positively reinforcing properties of both ethanol and water, ethanol drinking is a subset of consummatory behaviors that is particularly sensitive to opioid receptor blockade. The results suggest that activation of the endogenous opioid system may be an important mechanism which serves to maintain continued ethanol drinking.

In vivo ethanol elimination in man, monkey and rat: A lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dyhydrogenases

The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate.

More rapid elimination of alcohol in women as compared to their male siblings.

Sex differences in rates of ethanol elimination were investigated in natural siblings to reduce genetic variability as compared to subjects chosen at random. Ethanol was infused intravenously in a dose of 0.6 g/kg of body weight over 45 to 60 min and serial blood samples obtained for 5 hr. The mean rate of ethanol elimination was higher in seven women, not different in one, and lower in one compared with their male siblings. The mean rate of ethanol elimination for all nine women was higher at 1.93 +/- 0.12 as compared with the value of 1.69 +/- 0.17 mmoles/kg body weight/hr in the men (p less than 0.05). Higher rates of ethanol metabolism in women as compared to men may be important in the increased susceptibility of women to liver injury caused by alcohol consumption.

Reproducibility of ethanol elimination rates in long-sleep and short-sleep mice.

Ethanol metabolism was measured in long-sleep (LS) and short-sleep (SS) mice on two occasions separated by 1 week to test for repeatability. Mice were injected intraperitoneally with either 1.5 or 4.0 g/kg ethanol and the linear decline of blood ethanol level was measured. The parameters measured in each animal were linear ethanol elimination rate (EER), peak blood ethanol level, volume of distribution and Widmark ratio (r). Reproducibility was assessed using two statistical methods, paired t tests and Pearson correlations. Paired t tests indicated good reproducibility since the two replicate determinations did not differ significantly from each other. The other widely used indicator of reproducibility, the correlation coefficient (Pearson r) between the two measurements, was nonsignificant in almost every case, indicating poor reproducibility. This occurs because the range of values of EER is fairly narrow; thus, an individual is likely to fall anywhere within that narrow range from one day to the next, and the rank ordering of the individuals may not be maintained. Although parameters such as EER and volume of distribution appear to be reproducible for populations, they may have little or no utility as covariates in genetic analyses of individual differences in response to ethanol.

Selective mouse breeding for short ethanol sleep time has led to high levels of hepatic aromatic hydrocarbon (Ah) receptor

Following a selective breeding program of heterogeneous mice for more than 30 generations, SS (“short sleep”) and LS (“long sleep”) lines have been developed on the basis of their sleep times when challenged with a single intraperitoneal dose of ethanol. The aromatic hydrocarbon responsiveness ( Ah) locus encodes the Ah receptor, which regulates the induction of certain drug-metabolizing enzymes by polycyclic aromatic compounds such as 3-methylcholanthrene and tetrachlorodibenzo- p-dioxin. The C57BL/6 inbred mouse strain (B6; Ah b/ Ah b) has a high-affinity Ah receptor, while the DBA/2 inbred mouse strain (D2; Ah d/ Ah d) has a low-affinity Ah receptor. We show here that the SS inbred mouse line exhibits markedly elevated hepatic levels of the high-affinity Ah receptor, while the LS outbred mouse line contains the low-affinity Ah receptor. Among progeny of (B6D2)F 1 × D2 backcross, the b/ d heterozygote (having the high-affinity Ah receptor) was found to be several times more resistant than the d/ d homozygote to a single dose of intraperitoneal ethanol. The D2.B6- Ah b congenic line is also several times more resistant to intraperitoneal ethanol than the B6.D2- Ah d congenic line. We found that the waking blood ethanol levels are the same in b/ d and d/ d mice, suggesting that the relative ethanol resistance in b/ d mice cannot be explained on the basis of a difference in central nervous system sensitivity. There are no differences between SS and LS mice or between b/ d and d/ d mice with regard to (i) blood acetaldehyde levels after a single intraperitoneal dose of ethanol, or (ii) hepatic alcohol dehydrogenase activities. There is a difference in the rate of ethanol elimination: SS more rapid than LS; b/ d more rapid than d/ d. Although SS mice have lower hepatic aldehyde dehydrogenase activities (cytosolic, mitochondrial low- K m ; and mitochondrial high- K m forms) than LS mice, b/ d and d/ d do not show this difference. These data suggest that a selected mouse breeding program, based on resistance to a single intraperitoneal dose of ethanol, selects concurrently for the hepatic high-affinity Ah receptor. This selective advantage cannot be explained on the basis of changes in alcohol dehydrogenase or aldehyde dehydrogenase activities and might provide insight into the nature of the endogenous ligand for the Ah receptor.

Comparative study on ethanol elimination and blood acetaldehyde between alcoholics and control subjects.

Factors influencing ethanol elimination rate and blood acetaldehyde concentration with regard to age, blood ethanol concentration, and degrees of alcoholic liver disorder were studied in alcoholic patients vis-à-vis healthy subjects. Ninety-four male alcoholic patients were divided into five groups according to age and into three groups according to blood ethanol concentration which ranged between 4.21 and 0.29 mg/ml. It was noted that as age increased, blood ethanol concentration decreased. Groups A, B, and C consisted of subjects whose ethanol levels were more than 2.5, between 1.0 and 2.5, and less than 1.0 mg/ml, respectively. Average values of ethanol elimination rate in Groups A, B, and C were 0.26, 0.23, and 0.18 mg/ml/hr, respectively. The rate increased as blood ethanol concentration elevated. The rate in Group B was significantly higher than that in the healthy control subjects who had blood ethanol levels between 1.0 and 2.5 mg/ml. The rate of ethanol elimination was independent of liver disorder judged by liver function test values. Blood acetaldehyde concentrations in the patients were less than 1.48 micrograms/ml, with an average value of 0.58 microgram/ml, and were significantly correlated with blood ethanol levels in both alcoholics and healthy subjects.

Swift increase in alcohol metabolism in humans.

One hundred and fifteen human male subjects, 19-30 years of age, received ethanol orally as vodka (0.55, 0.7, or 0.85 g/kg) followed by a second drink (0.3-0.4 g/kg) given 3-4 hr later. After both doses, blood ethanol levels reached approximately 100 mg/dl. Breath samples were taken every 20-30 min and rates of ethanol elimination were determined. In addition to the design described above, 100 subjects received 0.7 g/kg ethanol in two separate visits to the laboratory. In a third experimental design, ethanol was given i.v. to 12 subjects. With the single-day experimental design, the frequency distribution of changes in rates of ethanol elimination between the first compared with the second administration of ethanol was not unimodal. Up to 20% of the subjects demonstrated rates more than 40% greater than basal values in response to ethanol. Based on these findings in humans, a Swift Increase in Alcohol Metabolism (SIAM) was defined as an increase in the rate of ethanol elimination of at least 40% over the basal rate. Under these conditions, the frequency of SIAM was dose dependent (studied with 0.55, 0.7, and 0.85 g/kg); nearly 20% of the subjects demonstrated SIAM with a dose of ethanol of 0.85 g/kg. In the two-day experimental design, a SIAM response was also observed in about 10% of 49 well-fed subjects; however, none of 51 subjects tested exhibited a SIAM response following an overnight fast. In addition, a rapid and transient SIAM reflecting a 60% increase in the rate of ethanol elimination above basal values was observed when ethanol was given continuously for 5 hr i.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of testosterone administration on rates of ethanol elimination in hypogonadal patients

Rates of ethanol elimination were determined in four hypogonadal subjects at one week and again at eight weeks after the administration of one dose of 200 mg of testosterone cypionate (Depo-testosterone). Ethanol elimination was unchanged in two patients, slightly decreased in one, and markedly increased in one patient at eight weeks as compared to one week after testosterone administration. In the three patients with little or no change in ethanol elimination, initial high levels of plasma-free testosterone, ranging from 445.0 to 3.8 ng/dl did not decrease to abnormally low levels, but ranged between 1.6 and 7.7 ng/dl (normal, 1.20–2.10 ng/dl). In the fourth patient, an increase in ethanol elimination from 86.6 to 107.4 mg/kg body weight/hr was associated with a decrease in plasma-free testosterone from a high level of 4.7 to 0.8 ng/dl. These results indicate that pharmacological plasma concentration of testosterone do not affect the rate of ethanol elimination. A suppressing effect of testosterone on rate of ethanol elimination may occur at levels of plasma-free testosterone which extend from abnormally low up into the normal physiologic range.

Pharmacological and metabolic interactions between ethanol and methyl n-butyl ketone, methyl isobutyl ketone, methyl ethyl ketone, or acetone in mice

Methyl n-butyl ketone (MnBK), methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK), and acetone are widely used industrial solvents to which certain groups of workers are exposed. Pharmacological and metabolic interactions between these solvents and ethanol were explored in male CD-1 mice. The effects of these solvents on the duration of ethanol-induced loss of righting reflex and on ethanol elimination in mice were studied. The solvents were dissolved in corn oil and injected intraperitoneally 30 min before ethanol 4 g/kg ip. The four solvents prolonged significantly the duration of ethanol-induced loss of righting reflex when given in the following doses (mmol/kg): MnBK, 3.75 and 5; MIBK, 5; MEK, 5 and 10, acetone, 20 and 40. This prolongation was dose related and increased as the dose of the solvent was increased. The concentrations of ethanol in blood or brain on return of the righting reflex were similar in solvent-treated and control animals, with the exception of the group of mice treated with 40 mmol/kg acetone in which the ethanol concentrations were significantly lower than in control animals. The mean elimination rate of ethanol was markedly reduced in mice treated with MnBK 5 mmol/kg, MEK 15 mmol/kg, and acetone 40 mmol/kg. All four solvents reduced the activity of mouse liver alcohol dehydrogenase in vitro. It is concluded that enhancement of the ethanol-induced loss of righting reflex by these solvents in mice is well correlated to reduced elimination rate of ethanol.