Concentrations of acetaminophen in plasma measured by HPLC
Concentrations of acetaminophen glucuronide and sulfate in plasma measured by HPLC
Concentrations of acetaminophen glucuronide, sulfate, cysteine, glutathione, mercapturate in urine measured by HPLC
CYP, UGT, and SULT gene polymorphisms assayed using patient DNA
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.
2 x 500 mg by mouth once
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