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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
95
2 x 500 mg by mouth once
Tufts Clinical Pharmacology Study Unit
Boston, Massachusetts, United States
Acetaminophen Plasma Clearance Association With Race/Ethnicity
Plasma total clearance of acetaminophen in plasma measured by HPLC
Time frame: 2 days
Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity
Acetaminophen glucuronidation partial clearance determined from plasma clearance and urinary metabolite excretion
Time frame: 2 days
Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity
Acetaminophen sulfation partial clearance determined from plasma clearance and urinary metabolite excretion
Time frame: 2 days
Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity
Acetaminophen oxidation partial clearance determined from plasma clearance and urinary metabolite excretion
Time frame: 2 days
Acetaminophen Plasma Clearance Association With UGT2B15 Genotype
The association of UGT2B15 genotype with acetaminophen total clearance
Time frame: 2 days
Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype
The association of acetaminophen glucuronidation partial clearance with UGT2B15 genotype
Time frame: 2 days
APAP Plasma Adduct Association With UGT2B15 Genotype
The association of UGT2B15 genotype with APAP plasma adduct concentrations
Time frame: 2 days
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