Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Although acetaminophen is the most commonly used nonprescription drug in the USA, little is known regarding the influence of genes and race/ethnicity on acetaminophen disposition. The investigators long-term goal is to understand the causes of differences in acetaminophen disposition between people that are the result of genetic variation and ethnicity and may predispose individuals to a higher risk of acetaminophen hepatotoxicity. The aim of this particular study is to measure the rate of elimination of acetaminophen via the 3 main pathways (glucuronidation, sulfation and oxidation) in self-identified White-Americans (n=100) and African-Americans (n=100). These rates will then be correlated with selected genetic polymorphisms in genes encoding enzymes involved in acetaminophen metabolism. Two main hypotheses will be tested: 1. African-Americans eliminate acetaminophen more rapidly by glucuronidation than do White-Americans. 2. Elimination via glucuronidation, sulfation, and oxidation in subjects will be significantly correlated with the presence of polymorphisms in the UGT1A6, SULT1A1, and CYP2E1 genes, respectively.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Tufts University
• Collaborator: National Institute of General Medical Sciences (NIGMS)
• Treatments: Acetaminophen

Criteria

Inclusion Criteria:

• self-declared white/Caucasian

• self-declared African-American

• active

• ambulatory

• no evidence of medical disease

Exclusion Criteria:

• alcohol use of 3 or more drinks per day

• HIV or hepatitis (B or C) infection

• isoniazid

• disulfiram

• phenobarbital

• phenytoin

• carbamazepine

• rifampicin

• valproic acid

• probenecid

• St. John's Wort