Gender Differences in Pharmacokinetics of Alcohol (original) (raw)
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Journal of Clinical Laboratory Analysis, 2003
Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are most abundant in the liver, are the main enzymes involved in ethanol metabolism in humans. Gender-related differences in total liver ADH and ALDH activity among different animal species have been observed in many studies. We measured total ADH and ALDH activity, and the activity of class I-IV ADH in the livers of male and female patients. Total ADH and class I and II ADH activities were significantly higher in males than in females (P=0.0052, P=0.0074, P=0.020, respectively). Class III and IV ADH and total ALDH activities were not significantly different between the genders (P=0.2917, P=0.0590, P=0.2940, respectively). The results of our study clearly show that there is a difference in enzymatic activity between male and female patients for those isoenzymes that actively participate in ethanol oxidation in the liver (class I and II ADH), although the main form of ADH in this organ is class III ADH.
Clinics in Dermatology, 1999
A lcohol is a small molecule that is both water and lipid soluble. Therefore, it readily permeates all organs of the body and affects many of their vital functions. The most important ones, the likely mechanisms, as well as associated alcohol-drug interactions will be reviewed, with only brief mention of the classic, well-documented cutaneous signs of alcoholism and some newer emerging associations, which are discussed in detail elsewhere in this issue.
Gender differences in blood glucose and uric acid levels induced by varying doses of alcohol in man
Trastornos Adictivos, 2009
Objective. To study the gender differences in plasma glucose and uric acid levels caused by varying doses of alcohol. Materials and methods. 64 (36 male and 28 female) healthy, light drinkers (< 20 g ethanol/day) between the ages of twenty-five and thirty-six years were selected as volunteers. Results. The administration of 0.325, 0.650 and 1,300 g ethanol/kg body weight, reduced plasma glucose by 2, 11 and 16% respectively, in males and by 1, 4 and 7% in female subjects, respectively. These doses respectively increased plasma uric acid by 6, 20 and 32% in males and by 14, 40 and 56% in females (p > 0.05: except for the 56% difference). Conclusions. Although, these changes were not demonstrated to be statistically significant, sex is implicated to influence the manner alcohol affects the metabolism of glucose and uric acid. Recently, hypoglycaemia and hyperuricaemia have been observed to be risk factors of brain damage and cardiovascular disorders, respectively. The involvement of chronic and excessive consumption of ethanol in brain damage and cardiovascular dysfunction via disturbances in plasma glucose and uric acid levels, respectively, deserve further investigations.
Alcoholism-clinical and Experimental Research, 1993
We evaluated three markers of ethanol intake [whole blood associated acetaldehyde (WBAA), serum β-hexosaminidase, and γ-glutamyl transpeptidase (GGT)] in four groups of subjects: teetotalers (n= 104), random insurance applicants or “normals”(n= 1,010), subjects enrolling in an alcohol treatment program or “alcoholics”(n= 31), and subjects attending outpatient drug/alcohol treatment follow-up clinics (n= 128). Significant differences (p < 0.004 for each assay and each comparison) were found in the mean values between teetotalers and normals and normals and alcoholics. Male teetotalers and normals had significantly (p < 0.002) higher levels of WBAA than females of the same group. Male normals had significantly higher levels of GGT than females (p < 0.001). GGT increased with age in the normal population into the fifth decade and decreased thereafter. WBAA was the most sensitive assay with 97% of alcoholics having values above the 99th percentile for the teetotaler population (vs. 66% for serum β-hexosaminidase and 70% for GGT). None of the alcoholic subjects had values for all three assays below the 99th percentile for teetotalers compared with 21% of those in follow-up and 72% of normals. We conclude that WBAA appears to be the best of the three markers studied and that measurement of multiple markers for ethanol use appears clinically useful and incremental.
Gender differences in alcohol affection on an individual
Soudni lekarstvi / casopis Sekce soudniho lekarstvi Cs. lekarske spolecnosti J. Ev. Purkyne, 2013
It is a well-known fact that after drinking the same amount of alcohol, women show more signs of the effects of alcohol than men of the same weight. It seems that the main factors responsible for sex differences in alcohol metabolism and influence are the relatively lower amount of body water related to body fat in women than men and lower gastric ADH activity in women, both of which enable women to reach higher BAC after drinking equivalent amounts of alcohol with men. On the other hand, first-pass metabolism of alcohol during passing through the liver is more rapid in women, probably due to bigger liver mass in women than in men. It is proven that alcohol and sex hormones have bilateral influence on each other. Women with more rapid alcohol elimination ability show higher levels of sex hormones in blood than the rest. It seems that the specific body constitution of the female organism as well as the unique combination of their sex hormones is responsible for the gender differences...
American Journal of Physiology-Endocrinology and Metabolism, 2007
Individuals who carry the most active alcohol dehydrogenase (ADH) isoforms are protected against alcoholism. This work addresses the mechanism by which a high ADH activity leads to low ethanol intake in animals. Male and female ethanol drinker rats (UChB) were allowed access to 10% ethanol for 1 h. Females showed 70% higher hepatic ADH activity and displayed 60% lower voluntary ethanol intake than males. Following ethanol administration (1 g/kg ip), females generated a transient blood acetaldehyde increase (“burst”) with levels that were 2.5-fold greater than in males ( P < 0.02). Castration of males led to 1) an increased ADH activity (+50%, P < 0.001), 2) the appearance of an acetaldehyde burst (3- to 4-fold vs. sham), and 3) a reduction of voluntary ethanol intake comparable with that of naïve females. The ADH inhibitor 4-methylpyrazole blocked the appearance of arterial acetaldehyde and increased ethanol intake. Since the release of NADH from the ADH·NADH complex constitut...
Alcoholism: Clinical and Experimental Research, 2002
4-Methylpyrazole (4-MP), a selective inhibitor of alcohol dehydrogenase (ADH), recently has been approved for clinical use in humans. The objective was to evaluate the use of 4-MP in human alcohol research and to study the effect of 4-MP on various parameters of alcohol metabolism during alcohol intoxication. 4-MP (10-15 mg/kg orally) or placebo was given in double-blind fashion to 22 premenopausal women, 12 of whom were using oral contraceptives, and 13 men followed by intake of alcohol (0.5 g/kg orally) or placebo. A 30% to 40% decrease in the ethanol elimination rate was observed in the different groups during pretreatment with 4-MP. The alcohol-induced increase in plasma acetate was partially inhibited by 4-MP. A significant positive correlation was observed between the effect of 4-MP on the alcohol-induced lactate and acetate elevations. The acetaldehyde was nondetectable (&amp;lt;1 micromol/liter) in the peripheral venous blood during alcohol intoxication in both women and men. During alcohol intoxication, a decrease in breath acetaldehyde was found with 4-MP pretreatment in women but not in men. The alcohol-induced elevation in blood acetate level is caused, in part, by ADH-mediated ethanol oxidation. Although no evidence was found for measurable acetaldehyde levels in the peripheral venous blood during alcohol intoxication, the effect of 4-MP on breath acetaldehyde in women supports the view that ADH-mediated acetaldehyde elevations reflected in the airways, but too low to be detected in the peripheral venous blood, may occur in women during alcohol intoxication in the present experimental conditions.
Alcoholism: Clinical and Experimental Research, 2011
Background-Growth Hormone (GH)-Insulin-like Growth Factor 1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GH-IGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Methods-Forty-eight healthy volunteers (24 males and 24 females each in the 21-25 and 55-65 year age groups, underwent a two-session single-blinded study. Subjects received, in randomized counterbalanced order, alcohol infusions, individually computed based on a physiologicallybased pharmacokinetic (PBPK) model, to maintain a steady-state ("clamped") exposure of 50 mg % or saline for 3 hrs in separate sessions. Blood samples collected at baseline and post-infusion in each session were assayed for levels of GH, IGF-1, free testosterone and estradiol. Results-Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment × baseline interaction (p<0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in males, On the other hand, change in estradiol showed a significant treatment × sex interaction (p=0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in females. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p<0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p=0.046) indicating that males had greater changes in GH across treatment compared to females. Conclusion-Alcohol induced a complex pattern of hormonal responses that varied between younger and older males and females. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in females.