Pharmacy Practice Faculty Publications

Title

Acetaminophen Usage Patterns and Concentrations of Glutathione and γ-Glutamyl Transferase in Alcoholic Subjects

Document Type

Article

Publication Date

11-2007

Journal Title

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

ISSN

0277-0008

Volume

27

Issue

11

First Page

1473

Last Page

1482

DOI

http://dx.doi.org/10.1592/phco.27.11.1473

PubMed ID

17963456

Abstract

Study Objectives. To determine if subjects with chronic alcoholism are predisposed to acetaminophen-induced hepatotoxicity, and to determine the contributing factors.

Design. Prospective cohort study.

Setting. Community-based crisis intervention center.

Subjects. One hundred eighty-eight subjects who answered “yes” to at least one of the four questions on the CAGE (Cut down-Annoyed-Guilty-Eye-opener) questionnaire for identifying alcoholism, and 10 healthy volunteers (controls).

Intervention. A history, physical examination, urine toxicologic analysis, ethanol and drug therapy history, and venous blood samples were collected on all subjects.

Measurements and Main Results. Venous blood was analyzed for a liver profile, prothrombin time, and total and oxidized glutathione concentrations. A significantly higher proportion of daily drinkers were regular daily users (29.2% [45/154] vs 11.8% [4/34], p=0.0497) as well as abusers (35.7% [55/154] vs 14.7% [5/34], p=0.0237) of acetaminophen compared with nondaily drinkers. Alcoholic subjects with elevated γ-glutamyl transferase (GGT ≥ 51 U/L) levels had significantly lower median plasma glutathione concentrations (2.33 μmol/L, 95% confidence interval [CI] 1.74-2.69 μmol/L) compared with those of alcoholic subjects with normal GGT concentrations (5.97 μmol/L, 95% CI 4.39-7.03 μmol/L, p

Conclusions. Daily drinkers were more than twice as likely as nondaily drinkers to be regular daily acetaminophen users and abusers. Alcoholic subjects with elevated GGT concentrations had significantly lower plasma total glutathione concentrations, and plasma total glutathione concentrations inversely correlated with GGT concentrations. Elevated GGT concentrations may be a clinical marker of depleted glutathione in alcoholic subjects. Acetaminophen-induced hepatotoxicity appears to be uncommon in alcoholic subjects, despite the 31.9% (60/188 patients) who took doses that are potentially hepatotoxic.

Keywords

Acetaminophen, adult, alcohol drinking, alcoholism, analgesics, non-narcotic, biomarkers, pharmacological, cohort studies, community health centers, dose-response relationship, drug, drug-induced liver injury, female, glutathione, humans, liver, liver diseases, liver function tests, male, middle aged, prospective studies, substance-related disorders, gamma-glutamyltransferase