Phase 4
Completed N=95
Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
Source: ClinicalTrials.gov NCT00768716 ↗Enrolled (actual)
95
Serious AEs
0.0%
Results posted
May 2019
Primary outcomePrimary: Acetaminophen Plasma Clearance Association With Race/Ethnicity — 5.3; 5.9 mL/min/kg — p=0.52
◆ Published Evidence
Established
69citations · ~8 / year
Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers.
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.
Linked Publications
-
Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Acetaminophen Plasma Clearance Association With Race/Ethnicity |
5.3; 5.9 | 0.52 |
| PRIMARY Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity |
2.9; 3.3 | 0.42 |
| PRIMARY Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity |
1.4; 1.7 | 0.06 |
| PRIMARY Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity |
0.9; 0.57 | — |
| PRIMARY Acetaminophen Plasma Clearance Association With UGT2B15 Genotype |
6.4; 5.5; 4.7 | <0.0001 sig |
| PRIMARY Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype |
3.8; 2.8; 2.1 | <0.0001 sig |
| PRIMARY APAP Plasma Adduct Association With UGT2B15 Genotype |
16; 19; 27 | 0.003 sig |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT00768716) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.