Search resultsActivity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: A comparison with nonalcoholics
Title
Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: A comparison with nonalcoholics
Publication type
Journal Article
Year of Publication
2005
Authors
Journal
Hepatology
Volume
41
Issue
5
Pagination
1144 - 1150
Date published
2005
ISBN
02709139 (ISSN)
Keywords
Adult, alcohol consumption, Alcohol Drinking, Anti-Anxiety Agents, article, Aryl Hydrocarbon Hydroxylases, bioavailability, Biological Markers, body mass, chlorzoxazone, clearance, comparative study, concentration (parameters), concentration response, controlled study, correlation analysis, Cytochrome P-450 CYP2E1, Cytochrome P-450 CYP3A, cytochrome P450 2E1, cytochrome P450 3A, enzyme activity, Female, gender, gene expression, human, Humans, Liver, Lymphocytes, male, messenger RNA, midazolam, Muscle Relaxants, Central, Oxidoreductases, N-Demethylating, peripheral lymphocyte, Predictive Value of Tests, priority journal, race, RNA, Messenger
Abstract
Alcohol consumption is known to induce hepatic CYP2E1 activity, but its effect on hepatic and intestinal CYP3A in humans is not known. We have conducted a study to compare the CYP2E1 and CYP3A activities in 20 individuals with moderate alcohol consumption and 20 gender-, race-. and body mass index (BMI)-matched nonalcoholics. Intravenous and oral midazolam (MDZ) clearances were used to measure the in vivo CYP3A activity, and chlorzoxazone (CHZ) oral clearance was used to assess in vivo CYP2E1 activity. Furthermore, we assessed the relationship between hepatic CYP2E1 and CYP3A activities and their messenger RNA (mRNA) expression in the peripheral lymphocytes. The systemic clearance (CL) of MDZ was not different between alcoholics (36.9 ± 12 L/hr) and nonalcoholics (36.6 ± 14.1; P = .9). The oral availability of MDZ was significantly lower in alcoholics than in the nonalcoholics (0.28 ± .09 vs. 0.38 ± .17, respectively, P = .03). The maximum serum concentration after oral midazolam dosing was significantly different between the 2 groups. CHZ CL was significantly higher in alcoholics than in nonalcoholics (31.5 ± 11.9 vs. 23.4 ± 8.7 L/hr, P < 0.05). CYP3A4 and CYP2E1 mRNA levels were not significantly different between the groups, and no correlation was observed between lymphocyte CYP mRNA and in vivo CYP activity. In conclusion, in individuals with moderate alcohol consumption, there was no alteration in the hepatic CYP3A activity, but the reduced midazolam oral bioavailability suggests that moderate alcohol consumption may cause intestinal CYP3A induction. Lymphocyte CYP2E1 and CYP3A4 mRNA levels did not correlate with CYP2E1 and CYP3A activities. Copyright