S.L. and D.K. have contributed equally and should be considered as the first authors.
Liver Failure and Liver Disease
Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: A comparison with nonalcoholics†
Article first published online: 19 APR 2005
Copyright © 2005 American Association for the Study of Liver Diseases
Volume 41, Issue 5, pages 1144–1150, May 2005
How to Cite
Liangpunsakul, S., Kolwankar, D., Pinto, A., Gorski, J. C., Hall, S. D. and Chalasani, N. (2005), Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: A comparison with nonalcoholics. Hepatology, 41: 1144–1150. doi: 10.1002/hep.20673
Potential conflict of interest: Nothing to report.
- Issue published online: 19 APR 2005
- Article first published online: 19 APR 2005
- Manuscript Accepted: 16 FEB 2005
- Manuscript Received: 22 NOV 2004
- Alcohol Research Center Pilot Projects Grant. Grant Number: P60 AAO7611
- General Clinical Research Center. Grant Number: RR00750
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. (HEPATOLOGY 2005;41:1144–1150.)