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.