Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

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.

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