Article

Human pharmacokinetics of ethanol. I. Peak blood concentrations and elimination in male and female subjects

Authors:
To read the full-text of this research, you can request a copy directly from the author.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the author.

... F OR AN EQUAL alcohol intake, women develop higher blood alcohol levels than men (Dubowski, 1976;Jones and Jones, 1976) despite a faster rate of ethanol elimination (Dubowski, 1976;Mishra et al., 1989). This dissociation has been attributed to the smaller volume of alcohol distribution in women (Arthur et al., 1984;Goist and Sutker 1985;Marshall et al., 1983). ...
... F OR AN EQUAL alcohol intake, women develop higher blood alcohol levels than men (Dubowski, 1976;Jones and Jones, 1976) despite a faster rate of ethanol elimination (Dubowski, 1976;Mishra et al., 1989). This dissociation has been attributed to the smaller volume of alcohol distribution in women (Arthur et al., 1984;Goist and Sutker 1985;Marshall et al., 1983). ...
... This reflects the interplay of gender differences in several aspects of ethanol metabolism. We confirmed the observation by others (Dubowski 1976;Mishra et al., 1989) that the rate of ethanol oxidation, a function predominantly exerted by the liver, is faster in women than in men. In the present study, the maximal rate of elimination (VMAX) was 10% higher in women than in men. ...
Article
Full-text available
Background: The enhanced vulnerability of women to develop alcohol-related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated. Methods: Sixty-five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the route-dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 μCurie of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for γ-ADH (acetaldehyde) and for ς-ADH (m-nitrobenzaldehyde) and a specific reaction of χ-ADH (glutathione-dependent formaldehyde dehydrogenase). Results: Women had less first-pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric χ-ADH activity; its low affinity for ethanol could explain the greater gender difference in first-pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route-dependent effects. Conclusions: The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of χ-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.
... The finding is robust and verified in many studies that women have a slightly steeper slope in the post-absorptive segment of the alcohol curve than men assuming zero-order kinetics. This implies a faster rate of elimination of ethanol from blood compared with men (Dubowski, 1976;Marshall et al., 1983;Cole-Harding et al., 1987). However, a steeper ß-slope in combination with a smaller volume of distribution in females (lower "r" factor) means that the overall rate of clearance of ethanol from the body expressed as g/kg/h and defined as the product of ß and r was not statistically significant between the sexes (Jones, 1989). ...
... The major gender difference in ethanol pharmacokinetics concerns the value of the distribution factor "r" (Whitfield et al., 1990;Dubowski, 1976). This factor strongly depends on body composition, especially the amount of water per kg of body weight and therefore the proportions of fat to lean tissue in the organism (Watson et al., 1981;Wang et al., 1992). ...
... Women become more impaired than men after consuming equivalent amounts of alcohol even when doses are adjusted for body weight (Van Thiel and Gavaler, 1988;Holman et al., 1996;Ammon et al., 1996;Hommer et al., 2001). After drinking equal amounts of alcohol, women seem to reach higher blood alcohol levels than men (Dubowski, 1976;Jones and Jones, 1976a;Goist and Sutker, 1985), although not all studies have been able to replicate these findings (Sutker et al., 1983;Marshall et al., 1983;Baraona et al., 2001). When comparing oral intake of alcohol with intravenous administration, no difference in BAC between men and women was seen after intravenous administration (Arthur et al., 1984;Goist and Sutker, 1985;Frezza et al., 1990;Baraona et al., 2001). ...
... The first-pass metabolism (FPM) also seems to be smaller in women than men because of a lower level of the gastric alcohol-metabolizing enzyme, alcoholdehydrogenase (ADH) (Frezza et al., 1990;Baraona et al., 2001), a more rapid oxidation of alcohol in the liver, and a delayed gastric emptying after consuming the same type of meal (Knight et al., 1997). Women also seem to have a faster elimination rate of alcohol (Dubowski, 1976;Sutker et al., 1983;Mishra et al., 1989;Kwo et al., 1998). However, Jones and Jones do not support this conclusion (1976b). ...
... Widmark, appreciating the importance of uncertainty, derived separate equations for men and women to estimate one standard deviation estimates in A as follows [2]: [12]. d Assumed estimated from duplicate breath alcohol analyses [13]. ...
... d Assumed estimated from duplicate breath alcohol analyses [13]. e Values reported in the study of n = 25 males [12]. f The assumed drink was a 12 fluid ounce beer with 4% alcohol by volume. ...
Article
Full-text available
No computation is performed more frequently by forensic toxicologists than that involving Widmark's equation. The equation is employed to estimate either the number of drinks consumed or the corresponding blood or breath alcohol concentration. Despite the wide use of Widmark's equation, rarely is an uncertainty estimate also provided. Estimates from Widmark's equation involve at least seven uncertain random variables. Uncertainty estimates are presented that rely on methods of general error propagation compared to a method developed by Widmark. Assuming reasonable variable and uncertainty estimates, the error propagation method yielded for N=10.4 drinks, a combined uncertainty (standard deviation) of 1.3 drinks (CV=12.3%). Similarly, estimating the blood alcohol concentration yielded for 0.120 g/100 ml, an uncertainty of 0.0255 g/100 ml (CV=21.2%). Widmark's uncertainty method yielded 1.6 drinks (CV=15.4%). The derivation of Widmark's uncertainty estimate is also presented, showing that he considered only rho and beta to be uncertain. Widmark estimates for the number of drinks should include a 2CV estimate of approximately 25% while the blood alcohol concentration estimate should include a 2CV estimate of approximately 42%. Including valid estimates of uncertainty should enhance the legal admissibility and confidence for Widmark estimations.
... Studies on ethanol biotransformation have shown that men and women differ in their ability to metabolize this alcohol. In 1976, Jones and Dubowski showed that the concentration of ethanol in the blood after oral administration is higher in women than in men (Dubowski, 1976;Jones & Jones, 1976). No similar differences were observed after intravenous administration of ethanol. ...
Article
1. Ethanol, as a small-molecule organic compound exhibiting both hydrophilic and lipophilic properties , quickly pass through the biological barriers. Over 95% of absorbed ethanol undergoes bio-transformation, the remaining amount is excreted unchanged, mainly with urine and exhaled air. 2. The main route of ethyl alcohol metabolism is its oxidation to acetaldehyde, which is converted into acetic acid with the participation of cytosolic NAD þ-dependent alcohol (ADH) and aldehyde (ALDH) dehydrogenases. Oxidative biotransformation pathways of ethanol also include reactions catalyzed by the microsomal ethanol oxidizing system (MEOS), peroxisomal catalase and aldehyde (AOX) and xanthine (XOR) oxidases. The resulting acetic acid can be activated to acetyl-CoA by the acetyl-CoA synthetase (ACS). 3. It is also possible, to a much smaller extent, non-oxidative routes of ethanol biotransformation including its esterification with fatty acids by ethyl fatty acid synthase (FAEES), re-esterification of phospholipids, especially phosphatidylcholines, with phospholipase D (PLD), coupling with sulfuric acid by alcohol sulfotransferase (SULT) and with glucuronic acid using UDP-glucuronyl transferase (UGT, syn. UDPGT). 4. The intestinal microbiome plays a significant role in the ethanol biotransformation and in the initiation and progression of liver diseases stimulated by ethanol and its metabolite-acetaldehyde, or by lipopolysaccharide and ROS. ARTICLE HISTORY
... Studies on ethanol biotransformation have shown that men and women differ in their ability to metabolize this alcohol. In 1976, Jones and Dubowski showed that the concentration of ethanol in the blood after oral administration is higher in women than in men (Dubowski, 1976;Jones & Jones, 1976). No similar differences were observed after intravenous administration of ethanol. ...
Article
Full-text available
• Ethanol, as a small-molecule organic compound exhibiting both hydrophilic and lipophilic properties, quickly pass through the biological barriers. Over 95% of absorbed ethanol undergoes biotransformation, the remaining amount is excreted unchanged, mainly with urine and exhaled air. • The main route of ethyl alcohol metabolism is its oxidation to acetaldehyde, which is converted into acetic acid with the participation of cytosolic NAD+ - dependent alcohol (ADH) and aldehyde (ALDH) dehydrogenases. Oxidative biotransformation pathways of ethanol also include reactions catalyzed by the microsomal ethanol oxidizing system (MEOS), peroxisomal catalase and aldehyde (AOX) and xanthine (XOR) oxidases. The resulting acetic acid can be activated to acetyl-CoA by the acetyl-CoA synthetase (ACS). • It is also possible, to a much smaller extent, non-oxidative routes of ethanol biotransformation including its esterification with fatty acids by ethyl fatty acid synthase (FAEES), re-esterification of phospholipids, especially phosphatidylcholines, with phospholipase D (PLD), coupling with sulfuric acid by alcohol sulfotransferase (SULT) and with glucuronic acid using UDP-glucuronyl transferase (UGT, syn. UDPGT). • The intestinal microbiome plays a significant role in the ethanol biotransformation and in the initiation and progression of liver diseases stimulated by ethanol and its metabolite - acetaldehyde, or by lipopolysaccharide and ROS.
... When dosage is based on total body weight, there appears to be considerable variability in pharmacokinetics. For example, Dubowski (1976 Dubowski ( , 1985) reported that elapsed time from end of alcohol intake to peak BAC varied from 14 to 138 min, and mean times for men and women were 57 and 42 min, respectively. These data suggest that, on average, the time to peak BAC after the end of drinking is 1.35 times as long for men as for women. ...
Article
Ninety subjects (45 males, 45 females) were given 0.0, 0.5, or 1.0 ml/kg body weight of 190-proof ethanol and tested for chance-level presence/absence detection thresholds with energy-masked presentations of traffic signs and blank inputs. Alcohol produced higher blood alcohol concentration (BAC) levels, and higher detection threshold durations, for females than for males. These results indicate that alcohol influences precortical visual processing and that the influence is greater for females than for males. The higher bioavailability of alcohol in women is likely due to less gastric oxidation of ethanol in women than in men.
... For death from injury, the results are different from usual expectations. Despite the greater blood-alcohol level resulting on average for women than for men from a given number of drinks (Dubowski, 1976;Cole-Harding and Wilson, 1987), men are at greater risk than women of alcohol-related injury death for a given number of drinks consumed the same number of times in a lifetime. The effects of the blood-alcohol difference are overwhelmed by the greater general propensity of men to die of injury, and probably also to some extent by gender differences in behaviour after drinking (e.g. ...
Article
The objective of this paper was to determine separately the lifetime risk of drinking alcohol for chronic disease and acute injury outcomes as a basis for setting general population drinking guidelines for Australia. Relative risk data for different levels of average consumption of alcohol were combined with age, sex, and disease-specific risks of dying from an alcohol-attributable chronic disease. For injury, combinations of the number of drinks per occasion and frequency of drinking occasions were combined to model lifetime risk of death for different drinking pattern scenarios. A lifetime risk of injury death of 1 in 100 is reached for consumption levels of about three drinks daily per week for women, and three drinks five times a week for men. For chronic disease death, lifetime risk increases by about 10% with each 10-gram (one drink) increase in daily average alcohol consumption, although risks are higher for women than men, particularly at higher average consumption levels. Lifetime risks for injury and chronic disease combine to overall risk of alcohol-attributable mortality. In terms of guidelines, if a lifetime risk standard of 1 in 100 is set, then the implications of the analysis presented here are that both men and women should not exceed a volume of two drinks a day for chronic disease mortality, and for occasional drinking three or four drinks seem tolerable.
... Breath, 5, 6, 14, 15).1-3, 5, 19, 28, 35).3,28,38,39). ...
Article
The accuracy of estimates of blood-alcohol concentration based on measurements of breath-alcohol concentration in a randomly selected subject by a random quantitative evidential breath-alcohol analyzer is evaluated with respect to the breath analyzer itself, its calibration, and the biological variables of the subject being tested. There are no suitable experimental data for rigorous determination of the overall accuracy, so I estimate it from the CV of the available data. I find that the uncertainty in these breath-analyzer readings for a random subject in the postabsorptive state is at least +/- 15%, +/- 19%, or +/- 27%, depending on whether +/- 2 CV, the experimental range, or +/- 3 CV, respectively, is used to express the overall uncertainty. Over 90% of this uncertainty is due to biological variables of the subject, and at least 23% of subjects will have their actual blood-alcohol concentration overestimated. Manufacturers' specifications for the accuracy and precision of these instruments are inconsistent with the experimental values reported in the literature and I recommend that an appropriate amount of uncertainty be reflected in the results from these breath analyzers, especially when they are used for law-enforcement purposes.
... Great caution should be exercised in correlating BACs with presumed alcohol dosage, and speculative Death from respiratory paralysis retrograde extrapolation of an experimentally determined B AC to an earlier time should be avoided because of its many pitfalls. 8 ...
Article
Full-text available
Four methods for blood-alcohol analysis--gas chromatography, enzymatic oxidation with alcohol dehydrogenase, chemical oxidation with acid dichromate, and osmometry--are briefly reviewed from the point of view of the clinical laboratory. Advantages and limitations of these methods are discussed, and their key features are tabulated. The correlation of the results of blood-alcohol analyses with stages of alcoholic influence and their corresponding signs and symptoms is presented in tabular form.
... Many studies have shown that the mean S-slope for moderate drinkers is between 0.10 and 0.20 mg/mL/h (mean 0.13 to 0.15 mg/mL/h) when the dose of alcohol is consumed in the morning after an overnight fast (5,7,8). Women tend to have a slightly steeper [3-slope compared with men according to several controlled studies (5,6,9,10). ...
Article
The rate of disappearance of alcohol from the blood (beta-slope) was determined in drinking drivers by taking two blood samples about 60 min apart (mean 68 min, span 30 to 120 min). The results were compared for men and women as a function of their age and the prevailing blood-alcohol concentration (BAC). The material consisted of 1090 double blood samples from 976 men and 114 women with mean age 36.6 +/- 12.9 y (+/- SD) and 38.0 +/- 12.3 y (+/- SD), respectively. The mean BAC for the male DUI suspects was 1.88 +/- 0.748 mg/mL (+/- SD) compared with 1.86 +/- 0.702 (+/- SD) for the females. The relationship between beta-slope (y) and BAC (x) was y = 0.175 + 0.009x with a small positive correlation (r = 0.13) and standard error estimate (Syx) of 0.049 mg/mL. The mean beta-slope for female DUI suspects was 0.214 +/- 0.053 mg/mL/h (+/- SD), compared with 0.189 +/- 0.048 mg/mL/h in the male suspects, and this small difference was statistically highly significant (t = 5.21, p < 0.001). The overall mean rate of alcohol elimination from blood in drinking drivers was 0.191 +/- 0.049 mg/mL/h (+/- SD), and the 95% limits of agreement (LOA) spanned from 0.09 to 0.29 mg/mL/h. The value of the beta-slope was slightly steeper starting from a high initial BAC but was not much influenced by the person's age.
... These differences in drinking habits might explain the lower incidence of several alcohol-related diseases in women than in men 33,34 . Nevertheless, despite this, for equal alcohol intake, women have higher blood levels of ethanol than men 35,36 and ethanol bioavailability is much greater in women than men because women have lower gastric alcohol dehydrogenase activity 22 and the volume of distribution of ethanol is also lower 37 . ...
Article
Full-text available
The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases. We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex. Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day-1) for men and in Danish centres (Copenhagen, 20.9 g day-1) for women. The lowest total alcohol intake was in the Swedish centres (Umeå, 10.2 g day-1) in men and in Greek women (3.4 g day-1). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes. The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.
Article
Scientific investigations have produced 50 years of accumulated evidence showing a direct relationship between increasing blood alcohol concentration (BAC) in drivers and increasing risk of a motor vehicle crash. There is scientific consensus that alcohol causes deterioration of driving skills beginning at 0.05% BAC or even lower, and progressively serious impairment at higher BACs. Drivers aged 16 to 24 years have the highest representation of all age groups in alcohol-related road crashes; young drivers involved in alcohol-related fatal crashes have lower average BACs than older drivers. Alcohol impairs driving skills by its effects on the central nervous system, acting like a general anesthetic. It renders slower and less efficient both information acquisition and information processing, making divided-attention tasks such as steering and braking more difficult to carry out without error. The influence of alcohol on emotions and attitudes may be a crash risk factor related to driving style in addition to driving skill. Biologic variability among humans produces substantial differences in alcohol influence and alcohol tolerance, making virtually useless any attempts to fix a “safe ” drinking level for drivers. The American Medical Association supports a policy recommending (1) public education urging drivers not to drink, (2) adoption by all states of 0.05% BAC as per se evidence of alcohol-impaired driving, (3) 21 years as the legal drinking age in all states, (4) adoption by all states of administrative driver's license suspension in driving-under-the-influence cases, and (5) encouragement for the automobile industry to develop a safety module that thwarts operation of a motor vehicle by an intoxicated person.
Chapter
Although alcohol is one of the earliest drugs used by man to change behavior and to modulate subjective states, less is known about its behavioral pharmacology than about many drugs of more recent origin. This is probably due to a complex interweaving of social attitudes and beliefs about alcohol which have evolved from a common familiarity with drinking and the effects of alcohol intoxication. For many years, the assumption that all is known, coupled with denial that alcoholism is a form of drug addiction, and ambivalence about problem drinking, tended to limit experimental interest in the study of alcohol and behavior (Mello, 1976b, 1978b). Gradually, over the past 15 years, an increasing number of studies have examined the behavioral effects of alcohol in normal social drinkers and in alcohol addicts. The early evidence that alcoholism is a form of addiction (Victor and Adams, 1953; Isbell et al., 1955; Mendelson, 1964) has been consistently reaffirmed (Mello and Mendelson, 1977 for review). As more empirical studies have examined the effects of alcohol during intoxication rather than relying on retrospective self-reports, the limitations of commonly shared expectancies about alcohol’s effects have become increasingly evident. The disparities between anticipated and observed effects of intoxication illustrate how far we now are from a comprehensive understanding of the behavioral pharmacology of alcohol (Mello and Mendelson, 1978 a for review).
Chapter
Accurate and reliable measurement of alcohol consumption over extended time periods is important for treatment, research, and forensic applications. In a clinical setting, assessing alcohol consumption is important for identifying problem drinking and monitoring treatment compliance in individuals undergoing substance-abuse treatment. In a research setting, determining consumption is necessary to assess treatment outcomes and to understand patterns and amounts of drinking behaviors in various cohorts. Forensic applications include monitoring alcohol use in special populations, including transportation workers, drunk drivers, and impaired professionals.
Article
It is generally acknowledged that relatively little is known about alcoholism and problem drinking in women. The origins, expression, and consequences of alcohol abuse for women remain obscure. Although these issues have not been resolved for alcohol problems generally, most of the existing information about alcohol abuse has come from clinical studies of men. The question of possible sex-related differences has seldom been raised explicitly (Edwards et al., 1973; Mulford, 1977; Wanberg and Horn, 1970).
Article
Seven men (aged 23 to 52 years) and four women (aged 26 to 44 years) were hydrostatically weighed to determine their percentage of body fat and lean body weight. Female subjects on average had a higher percentage of body fat (23.5%, range 18.6–30.0%) than males (16.9%, range 7.5–30.2%). Subjects fasted for at least 10 hours prior to an oral dose of alcohol at 1.23 g/kg of lean body weight. Beer containing approximately 5% ethanol was consumed on day one of the experiment and 50.5% whiskey mixed with a carbonated beverage was consumed on day two of the experiment. All alcohol analyses were conducted on the Intoxilyzer 5000®. Female subjects had a slightly higher rate of elimination (0.0195 g/210 L/h, range 0.0169–0.0212) than male subjects (0.0186 g/210 L/h, range 0.0151–0.0225). While there were individual subject differences, on average, equal doses of ethanol per kg of lean body weight given in the same manner, over the same length of time, yielded statistically indistinguishable alcohol concentration results, regardless of subject gender or type of alcoholic beverage consumed.
Article
Ten healthy volunteers (six males, four females) consumed 0.37 to 0.52 g of alcohol per kilogram of body weight per hour over an approximate three-hour period. Each subject provided frequent breath samples into an Intoxilyzer® 5000C breath testing instrument during the drinking session and for approximately four hours following the end of drinking. The blood alcohol concentrations were determined from the Intoxilyzer® 5000C results using a blood:breath ratio of 2100:1. The highest blood alcohol concentrations ranged from 85 to 190 mg% (mean 128 mg%), and were achieved 12 minutes after the end of drinking (range 4 to 22 minutes). The mean time from the end of drinking to the start of linear decline was 69 minutes (range 0 to 124 minutes). The mean alcohol elimination rate was 19 mg%/hr (range 15.4 to 21.7 mg%/hr).
Article
Full-text available
A discussion of the problems that occur in criminal court regarding the absorption state of arrested drinking drivers and the blood/breath alcohol ratio was presented.
Article
Full-text available
An intra-subject comparative study was performed using breath analysis to assess the forensic implications of data truncation on peak blood alcohol concentrations (Cmax). Accordingly, several other forensically relevant pharmacokinetic parameters associated with Cmax were investigated, including the time-to-peak (Tmax), plateau (PLAT) duration, and the rise in blood alcohol concentration (BAC) following the end of drinking (EOD). The study consisted of three drinking sessions, nine subjects per session, with drinking intervals of 30, 90, and 180 minutes, and ethanol doses of 1.0, 1.1, and 1.6 g/kg, respectively. Three-digit breath measurements were collected in duplicate at 10, 30, 45, 60, 75, 90, 105, 120, 135, 195, and 255 minutes following EOD using a fuel-cell based breath instrument (Intox ECIR®). Breath results were then computed using two different data treatment methods. The first method averaged duplicate three-digit breath measurements and reported results to the third digit. The second method used the lower of the two duplicate measurements and reported results to the truncated second digit. The results of the two data treatment methods were then compared using general statistics and alcohol concentration- time profiles. The overall rise in BAC following EOD for three-digit results was 0.009 g/210L with a range of 0.000–0.030 g/210L (standard deviation 0.008 g/210L). When breath measurements where truncated, 25 of the 27 subjects had a rise in BAC of 0.02 g/210L or less. In total, 6 subjects had no rise in BAC following the EOD when evaluating the three-digit results. In contrast, when BAC results were truncated, 11 subjects exhibited no increase in BAC following EOD. The overall Tmax was reduced from 41 minutes to 26 minutes, and overall PLAT durations were extended from 22 to 39 minutes, when the breath measurements were truncated.
Article
Nine male and nine female subjects received one of four doses of alcohol (0-25, 0-5, 0-75 or 1 g per kg of bodyweight for male subjects: females received 92% of these values) or placebo. Similar blood alcohol concentrations (BAC) for males and females were reached. Subjects were then tested on two batteries of psychological tests related to skills involved in driving. These included psychomotor, cognitive and subjective assessment tasks. The results showed a linear increase in the disruption of performance with dose for many of the tests, particularly those involving psychomotor function. In addition it was demonstrated that on certain tasks males were affected more by alcohol than females. It is concluded that moderate doses of alcohol (resulting in BACs of 0-05 to 0-08 g/100 ml) can produce significant deficits in perceptual and motor skills related to driving a vehicle.
Article
The measurement of alcohol consumption over long time periods is important for monitoring treatment outcome and for research applications. Giner, Inc. has developed a wearable device that senses ethanol vapor at the surface of the skin, using an electrochemical cell that produces a continuous current signal proportional to ethanol concentration. A thermistor monitors continuous contact of the sensor with the skin, and a data-acquisition/logic circuit stores days of data recorded at 2- to 5-min intervals. Testing of this novel ethanol sensor/recorder was conducted on nonalcoholic human subjects consuming known quantities of ethanol and on intoxicated alcoholic subjects. The transdermal sensor signal closely follows the pattern of the blood alcohol concentration curve, although with a delay. This paper describes the concept of electrochemical ethanol measurement and presents some of the clinical data collected in support of the sensor/recorder development.
Article
Expert witnesses and others involved in toxicology are frequently asked to perform retrograde extrapolation of blood alcohol concentration (BAC) or to estimate BAC based on a proposed drinking scenario. Although many individuals are reluctant to perform these calculations and some jurisdictions expressly prohibit them, a significant number of practitioners routinely estimate BAC based on this type of calculation, using as a basis the fundamental work of Widmark. Although improvements to the Widmark formula and other data pertaining to the pharmacology of alcohol have been published, these improvements are frequently ignored when estimating BAC. This article summarizes five published models for the estimation of BAC and proposes a sixth model that incorporates recent data on the rate of absorption of alcohol from the GI tract into the existing five models. The five improved models can be computerized and used to construct comparative snapshots of the BACs calculated by the different algorithms. This will allow practitioners to provide a more balanced picture of the variability in BAC calculations.
Article
This study investigated gender differences in acute response to alcohol. After practicing several cognitive and psychomotor tasks while sober, male (n = 11) and female (n= 13) social drinkers were administered a 0.65 g/kg dose of ethanol. Subjects were tested on both the ascending and descending limbs of the blood alcohol curve on measures of divided attention, short-term memory, body sway, pursuit tracking ability, and subjective level of intoxication. Blood alcohol level (BAL) was sampled frequently throughout the procedure. Females achieved consistently higher BALs than did males throughout, due mainly to higher BALs among women in the middle stage of the menstrual cycle. Women not using birth control medications also attained higher BALs than did males. When gender differences in BALs were controlled statistically, only memory functioning distinguished the groups: males recovered memory functioning more quickly on the descending limb of the blood alcohol curve than did females. Stage of menstrual cycle or use of birth control medications did not influence psychomotor or cognitive performance while women were intoxicated.
Article
Reliable information about the elimination rate of alcohol (ethanol) from blood is often needed in forensic science and legal medicine when alcohol-related crimes, such as drunken driving or drug-related sexual assault are investigated. A blood sample for forensic analysis might not be taken until several hours after an offence was committed. The courts usually want to know the suspect's blood-alcohol concentration (BAC) at some earlier time, such as the time of driving. Making these back calculations or retrograde extrapolations of BAC in criminal cases has many proponents and critics. Ethanol is eliminated from the body mainly by oxidative metabolism in the liver by Class I isoenzymes of alcohol dehydrogenase (ADH). Ethanol is an example of a drug for which the Michaelis-Menten pharmacokinetic model applies and the Michaelis constant (k(m)) for Class I ADH is at a BAC of 2-10mg/100mL. This means that the enzyme is saturated with substrate after the first few drinks and that zero-order kinetics is adequate to describe the declining phase of the BAC profile in most forensic situations (BAC>20mg/100mL). After drinking on an empty stomach, the elimination rate of ethanol from blood falls within the range 10-15 mg/100mL/h. In non-fasted subjects the rate of elimination tends to be in the range 15-20mg/100mL/h. In alcoholics during detoxification, because activity of microsomal enzyme (CYP2E1) is boosted, the ethanol elimination rate might be 25-35 mg/100mL/h. The slope of the BAC declining phase is slightly steeper in women compared with men, which seems to be related to gender differences in liver weight in relation to lean body mass. The present evidence-based review suggests that the physiological range of ethanol elimination rates from blood is from 10 to 35 mg/100mL/h. In moderate drinkers 15 mg/100mL/h remains a good average value for the population, whereas in apprehended drivers 19 mg/100mL/h is more appropriate, since many of these individuals are binge drinkers or alcoholics. In preparing this article, a large number of peer-reviewed publications were scrutinized. Only those meeting certain standards in experimental design, dose of alcohol and blood-sampling protocol were used. The results presented can hopefully serve as best-practice guidelines when questions arise in criminal and civil litigation about the elimination rate of ethanol from blood in humans.
Article
Driving while intoxicated (DWI) legislation requires proving the critical breath alcohol concentration (BrAC) at the time of driving. With time delayed analysis, retrograde extrapolation is occasionally employed but has several uncertainties associated with it. The present study attempts to address whether subjects actually arrested for DWI are likely to have BrAC values near the time of driving differing largely from those performed at a subsequent time. Selected officers arrested n = 161 subjects where roadside BrAC was determined with Pre-Arrest Breath Test (PBT) devices along with subsequent duplicate evidential analyses followed by an additional PBT analysis. These two sets of duplicates, one with large time interval (mean = 63.5 min.) and one with a 2-3 min difference, were then compared by several statistical methods. The results showing duplicate variability did not differ when the long time interval existed (F = 1.0, P > 0.05). A small but significant decrease in BrAC with respect to time appeared for the duplicate PBT data. Retrograde extrapolation applied to the data employing an assumed 0.015 g/210 l/h yielded a small but significant overestimate of the actual roadside PBT result. Finally, evidentiary analyses performed within 2 h of driving will provide good estimates and certainly not overestimates, of the BrAC existing at the time of driving and it appears that extrapolation may be unwarranted in these cases.
Article
We measured alcohol levels by the Cordebard method in 148 CSF samples from individuals who had abstained from alcohol for at least 7 days prior to the beginning of the study. Each blood sample was accompanied by a CSF sample from the same patient. CSF samples found to be normal after analysis were used as controls. Mean alcohol concentration in blood did not differ significantly between the control group and the groups with altered CSF. The group with altered CSF had statistically higher alcohol levels in CSF than in blood. CSF lactate, glucose and protein levels were not correlated with alcohol level. The results suggest the presence of endogenous alcohol in the CSF, with levels increasing in the presence of pathological processes involving the nervous system.
Article
Previous studies in rodents have indicated that the facial changes of fetal alcohol syndrome (FAS) closely resemble those of a mild form of holoprosencephaly. In order to examine this relationship in non-human primates, we evaluated a 133-day gestation macaque (Macaca nemestrina) with holoprosencephaly, median cleft lip and palate, and encephalocele. The mother had been given ethanol once per week (1.8 g/kg body weight) from weeks 2 to 19 postconception. Diagnosis of holoprosencephaly was made following ultrasound evaluation for polyhydramnios and delivery of the female fetus by caesarean section. Another fetus of identical age was delivered by caesarean section for use as a control. Both fetuses were studied by anthropometric, gross, radiographic, and histologic techniques. In the fetus exposed to alcohol, no extracranial anomalies were identified and the karyotype was normal. The brain was micrencephalic, with absent olfactory bulbs, tracts, optic nerves and chiasma, fused frontal lobes, and a single, dilated lateral ventricle; a parietooccipital encephalocele consisted of thin, dysplastic cortex bordering the ventricle; the cerebellum was dysplastic and superiorly displaced. Within the craniofacial complex, anophthalmia was bilateral; premaxillary components were absent, palatal shelves separate, the maxillae closeset, and the ethmoid bone small and deformed. Most of these defects are similar to those encountered in humans with holoprosencephaly and support the hypothesis of shared etiologic and pathogenetic relations between the facial anomalies of fetal alcohol syndrome and holoprosencephaly.
Article
Revue sur le metabolisme de l'ethanol et ses effets sur les fonctions endocriniennes. Son role dans la perturbation de la fonction gonadique et dans la regulation hypothalamohypophysaire chez l'homme et la femme est analyse
The role of gender as a variable that might affect the metabolism of ethanol and thus the consequences of ethanol metabolism is reviewed. First, the pharmacodynamics of ethanol are reviewed. Specific differences between males and females relative to ethanol pharmacokinetic parameters are discussed including gender differences in the volume of distribution and putative hormonal effects on achieved blood alcohol levels. In addition, attention is directed toward the metabolic capacity of alcohol dehydrogenase and the microsomal ethanol oxidizing system with respect to effects of both sex differences and hormonal manipulations on the activities of these ethanol metabolizing enzymes. Finally, the data upon which the concept of sex-related differences in susceptibility to alcohol induced end organ failure are presented.
Article
The role of gender as a variable that might affect the metabolism of ethanol and thus the hepatotoxicity of ethanol is evaluated. First, the pharmacodynamics of ethanol are reviewed with particular attention to hormone effects on ethanol absorption and metabolism. Specific differences between males and females relative to ethanol pharmacokinetic parameters are discussed, including gender differences in the volume of distribution and putative hormonal effects on achieved blood alcohol levels. In addition, attention is directed toward the metabolic capacity of alcohol dehydrogenase and the microsomal ethanol-oxidizing system with respect to effects of both sex differences and hormonal manipulations on the activity of these ethanol-metabolizing enzymes. Finally, the studies on the concept of sex-related differences in susceptibility to alcohol hepatotoxicity are examined.
Article
A daily dose of 1.5 g/kg of ethanol interfered with radial arm maze performance in rats. Ethanol inhibited the acquisition of a new win-shift response to obtain a food reward, especially when a previously learned response was present. This effect was greater in females than in males. Ethanol appears to suppress flexibility in the development of optimal performance of goal-directed behavior.
Article
The present study was a direct experimental comparison of administering equivalent alcohol doses based on body weight and estimated total body water to 12 women and 12 men. Each subject participated in two experimental sessions separated by at least three days. Two doses of 95% ethanol were administered in a randomized, counterbalanced order: 0.66 ml/kg of body weight, and 1.2 ml/l of total body water. Women were tested during the midfollicular phase of their menstrual cycle when plasma concentrations of estrogen and progesterone have been found to be lower than other phases of the cycle. When given doses equated for body weight, women reached significantly higher peak blood alcohol concentrations than men. No sex differences were found when equivalent doses based on total body water were administered. This differential effect of dose determination was not reflected in self-reported levels of alcohol intoxication. The anthropometric equations used to estimate total body water provided a practical, reliable method for equating alcohol doses.
Article
Forty-eight healthy men each drank a dose of ethanol, 0.68 g/kg of body weight, as neat whisky at about 09.00, after fasting overnight. The drink was finished within 20 min and the concentrations of ethanol in samples of capillary blood were determined at 30-60 min intervals for 7 hr. Rectilinear regression lines were fitted to the elimination phase of blood concentration time profiles and blood-ethanol parameters were calculated as described by Widmark. In 23, 14, 8 and 3 subjects the peak blood ethanol concentrations were reached at 30, 60, 90 and 120 min timed from starting to drink. The highest concentration of ethanol in blood was 0.92 +/- 0.022 mg/ml (mean +/- SE) and the coefficient of variation (CV) was 16.8%. The blood concentration of ethanol extrapolated to zero-time was 0.98 +/- 0.009 mg/ml (CV = 6.5%) and the apparent volume of distribution (Vd) was 0.695 +/- 0.0064 L/kg (CV = 6.4%). The rate of ethanol elimination from blood was 0.126 +/- 0.0018 mg/ml/hr (CV = 9.9%) and the body clearance was 87.5 +/- 1.1 mg/kg/hr (CV = 8.7%). The apparent volume of distribution of ethanol was inversely related to the subject's body weight (r = -0.59 +/- 0.118, p less than 0.001). The elimination rate from blood was lower in those subjects with larger distribution volume; the parameters were negatively correlated (r = -0.52 +/- 0.126, p less than 0.001). The results show that blood-ethanol parameters calculated according to Widmark's method have low intersubject variability when the dose of ethanol administered and the condition of the test subjects are carefully controlled.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Full-text available
Ethanol pharmacokinetics were determined following oral ethanol, 0.5 gm per kg, in nine normal women and 10 normal men, and related to total body water measured by 3H-water dilution and body fat determined anthropometrically. Ethanol pharmacokinetics were similar in the females throughout the menstrual cycle. No variation was seen in mean peak blood ethanol concentration or elimination rate in the midfollicular (Days 8 to 10) and midluteal (Days 22 to 24) phases. Mean peak blood ethanol values were significantly higher in females (88 +/- 3 mg per 100 ml) than in males (75 +/- 4 mg per 100 ml) (p less than 0.05), and the mean area under the ethanol concentration-time curve was significantly greater in females (241 +/- 12 mg X hr per 100 ml) than in males (177 +/- 11 mg X hr per 100 ml) (p less than 0.001). There was no significant sex difference in mean ethanol elimination rates. The mean apparent volume of distribution of ethanol in female (0.59 +/- 0.02 liter per kg) was less than in males (0.73 +/- 0.02 liter per kg) (p less than 0.001). Both apparent volume of distribution of ethanol and area under curve were significantly correlated with total body water suggesting that the sex differences in ethanol pharmacokinetics were due to sex differences in body water content. The sex differences in ethanol pharmacokinetics may partly explain reports of male-female differences in the natural history of certain ethanol-related disorders.
Article
Relationships between variations in blood alcohol level (BAL) and blood alcohol level discrimination accuracy were investigated as a function of menstrual cycle, hormonal variations, and behavioral tolerance to alcohol in 20 female social drinkers. All subjects consumed a moderate dose of alcohol on three occasions during one complete menstrual cycle. Subjects estimated their level of intoxication eight times during each drinking session. Each subject's behavioral tolerance to alcohol each session was assessed by a body sway procedure. Subjects also completed detailed questionnaires on symptoms related to menstrual period and familial history of alcohol use. Contrary to earlier reports, (1) no difference in total time of intoxication or in other indices of ethanol metabolism was found between women (N = 9) who were not taking birth control pills and those (N = 11) who were and (2) no difference was found in peak BAL as a function of menstrual cycle phase. Stage of menstrual cycle did not affect the accuracy of BAL estimation. A trend approaching significance suggested that, with increasing BAL, women in the oral contraceptive group were more accurate in their estimates of intoxication. A significant interaction between menstrual cycle phase and tolerance levels was found; high tolerant women were significantly less accurate than low tolerant women in estimating BAL during the midcycle phase of the menstrual cycle.
Article
The sudden increase in alcoholic liver disease among women in the past 10 years has caused much speculation that they may be more susceptible to the hepatotoxic effects of alcohol than men. Women tend to present with more severe liver disease, particularly alcoholic hepatitis, and do so after a shorter period of excessive drinking and at a lower daily alcohol intake. Differences in body size and composition are partly responsible for the greater susceptibility of women, but differences in immune reactivity between the sexes may also play a part. Greater emphasis must be placed on designing abstinence programmes specifically for female patients, on earlier detection of liver disease, and on educating women about hazardous drinking levels.
Article
In this preliminary study of alcohol effects on aviators' flight simulator performance, we addressed some methodological issues regarding possible gender-related differences in response to alcohol. Subjects were 11 male and 12 female general aviation pilots, ages 21-40. Subjects received 8 h of training before they were tested with alcohol. On the alcohol test day they were tested before drinking, while intoxicated (target BAC of 0.08%), and 8 h after drinking. The average, observed peak BAC readings for men and women were within 0.003% of each other. We observed faster disappearance rates for women such that women reached the FAA cutoff of 0.04% approximately 1 h before men, on average. Compared to predrink performance, there was a significant decrement in simulator performance during acute intoxication, but not 8 h after drinking. There were no significant gender differences in performance before or after drinking alcohol. Slower rates of alcohol elimination were associated with larger performance changes 8 h after drinking. This is the first report to our knowledge suggesting a possible relation between alcohol elimination rate and change in performance after drinking alcohol. A 12.5% dose reduction for women appears to be adequate for achieving comparable peak BAC's for male and female groups. Future studies using measures of circadian rhythmicity in conjunction with pharmacokinetic and performance measures could potentially shed light on differences in subjects' acute and delayed responses to alcohol.
Article
Ten nonalcoholic subjects gave written informed consent. Six men (aged 25-43) and four women (aged 25-35) were hydrostatically weighed to determine their percentage of body fat and lean weight. Each subject fasted for at least 10 h and then received an oral dose of alcohol (0.9 g per kilogram of lead body weight) calculated to yield a peak alcohol concentration of 0.100 g/210-L breath. Breath alcohol measurements were conducted at 20-min intervals until each subject's alcohol concentration returned to 0.000 g/210-L breath. All alcohol analyses were conducted on the Intoxilyzer 5000 and reported as g/210-L breath. Female subjects on average reached a lower peak alcohol concentration (mean, 0.086; range, 0.074-0.091 g/210 L) than male subjects (mean, 0.096; range, 0.093-0.101 g/210 L). Females demonstrated a higher average rate of elimination (mean, 0.017; range, 0.014-0.021 g/210 L) than males (mean, 0.015; range, 0.013-0.017 g/210 L). Female subjects on average had a higher percentage of body fat (mean, 26.0; range, 16.7-36.8%) than males (mean, 18.0; range, 10.2-25.3%). The average volume of distribution (Vd), as calculated from percentage of body fat, for the women (mean, 0.63; range, 0.54-0.71) was less than for the men (mean, 0.69; range, 0.63-0.76). The average Vd as calculated from linear regression of the alcohol concentration curve, for the women (mean 0.64, range, 0.56-0.71) was also less than for the men (mean, 0.72; range, 0.67-0.77). The data from this limited study indicate that hydrostatic weighing is an acceptable way of determining Vd for both men and women.
Article
Full-text available
In this paper, we review the current status of genetic markers for the development of alcohol abuse. Family, twin, half-sibling and adoption studies of alcoholic subjects suggest that the heritability of liability to alcoholism is at least 50%. These findings have fuelled intensive investigation in the fields of neurology, biochemistry, genetics and molecular biology aimed at the identification of markers for the risk of alcoholism. The most promising of these are discussed in detail. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) polymorphisms, specifically the ADH3*1, ADH2*2, and ALDH2*2 genotypes appear to confer a protective effect against alcoholism, most notably in Oriental subjects. Caucasian alcohol abusers and their first-degree relatives exhibit depressed platelet monoamine oxidase activity, the degree of which is greater in Type II than Type I alcoholics. Electrophysiological characteristics of alcoholics and those at risk for developing alcoholism have also been identified, including the reduced amplitude of the event-related brain potential and, after ethanol ingestion, characteristic EEG alpha-wave activity. Lower platelet adenylate cyclase activity is seen in alcoholics compared to controls, presumably as a result of over-expression of an inhibitory G-protein. Markers related to other signal transduction pathways of the central nervous system including the serotoninergic, muscarinic and dopaminergic systems are also discussed. In this group of markers, the putative association between the inheritance of the AI allele of the D2 dopamine receptor and the susceptibility to alcoholism provides the most dramatic illustration of the challenges presently existing in this field of scientific investigation. Current limitations in the definition, diagnosis and classification of alcoholism, the confounding influences of race and gender on association studies, as well as the statistical approach of linkage studies are discussed as they relate to the endeavor to uncover valid genetic markers for the risk of alcoholism.
Article
Because of biological differences between men and women, the same quantity of alcohol consumed over the same time period produces higher blood alcohol levels (BALs) in women than in men. Some alcohol researchers have proposed that quantity and volume measures of alcohol consumption (e.g. usual number of drinks per drinking day and overall amount of alcohol consumed) should be adjusted to reflect these biological differences. To date, no standard adjustment for biological gender differences has been adopted. In this paper, we review the literature on biological and behavioral differences related to alcohol consumption and effects and discuss the implications of these differences in terms of adjusting alcohol consumption measures. Our review suggests that adjusting measures of alcohol consumption to compensate for biological sex differences is most appropriate for research or policy applications involving the short and long-term physiological effects of alcohol in contexts where gender differences in how alcohol is consumed can be assumed to be minimal. In other circumstances, non-biological gender differences relating to alcohol use, such as pace of drinking, may moderate the relationship between alcohol consumption and biological gender differences, making an adjustment less defensible. We also identify areas where more knowledge is needed not only to address the issue of adjusting alcohol measures for gender differences but also to understand better the relationship between alcohol consumption and effects.
Article
A search of the alcohol research literature reveals that very little experimental work has been done to describe the effects of alcohol in older females. In the present study, the effects of age and body water volume on the resultant peak alcohol concentration were observed for females ranging in age from 21 to 81. The peak alcohol concentration was estimated by breath testing in three groups of female volunteer subjects: young (21 to 25 years old), middle-age (35 to 47 years old), and older (>60 years old) after ingestion of 30 g of alcohol. Bioelectrical impedance analysis and anthropometric equations were used to estimate total body water, percent body water, and percent body fat for each subject. Significantly higher blood alcohol concentrations were obtained in older females [mean blood alcohol concentration (+/-SD) = 0.0975+/-0.018], compared with younger females (0.0818+/-0.016 and 0.0811+/-0.012). The results suggest, however, that this effect cannot be fully explained by the notion that older persons have a smaller body water volume. Particular attention is paid to the difference between total body water in liters and body water expressed as a percentage of body weight. Evidence is offered to demonstrate that percent body fat is not a determinant of the blood alcohol level an individual will attain. The findings are discussed with particular reference to the lack of experimental work involving older females and alcohol.
Article
The enhanced vulnerability of women to develop alcohol-related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated. Sixty-five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the route-dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 microCurie of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for gamma-ADH (acetaldehyde) and for final sigma-ADH (m-nitrobenzaldehyde) and a specific reaction of chi-ADH (glutathione-dependent formaldehyde dehydrogenase). Women had less first-pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric chi-ADH activity; its low affinity for ethanol could explain the greater gender difference in first-pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route-dependent effects. The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of chi-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.
Article
The liver disease characteristic of alcohol dependence encompasses three main related entities: steatosis, alcoholic hepatitis, and cirrhosis. Alcoholic cirrhosis is a leading cause of global morbidity and mortality. Alcohol intake among injecting drug users is a major contributor to transmission of viral infections, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C viruses (HCV). HIV and HCV coinfected patients develop liver diseases earlier and more severely than the monoinfected individuals, including hepatocellular carcinoma. Interactions exist between the therapeutic drugs used to minimize and control the drug and alcohol dependence. Furthermore, drug-drug interactions occur between the highly active antiretroviral therapy (HAART) and alcohol, different HAART components and methadone, or each one of the therapies with the other, thus contributing to a higher toxicity level. With the evolution of effective antiretroviral therapy, survival of persons with HIV, and the syndrome it causes, acquired immunodeficiency syndrome (AIDS) has increased dramatically. Drug-drug interactions may appear between alcohol and anti-HBV or anti-HCV, therapy in the presence or absence of anti-HIV therapy. Several other medical-, social-, and drug-related factors of this population have to be considered when providing HAART. Because many coinfected patients also have problems with substance use, dealing with their drug dependence is an important first step in an attempt to improve adherence to and tolerance of antiviral therapy. It is necessary to minimize the risk of liver disease acceleration and/or reinfection with hepatitis viruses. Knowledge of potential drug interactions between methadone, antiretroviral therapy, psychoactive drugs, and antipsychotics and the role of coinfection with HBV or HCV and the drugs used in eradicating viral hepatitis permits suitable antiretroviral combinations.
ResearchGate has not been able to resolve any references for this publication.