Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

Phase 4

Completed

• Conditions: Hepatotoxicity; Pain; Fever
• Interventions: Drug: Acetaminophen

• Registration Number: NCT00768716
• Lead Sponsor: Tufts University

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-10-07
• Study First Submitted QC: 2008-10-07
• Study First Posted: 2008-10-08
• Study Start: 2008-12
• Primary Completion: 2012-06
• Study Completion: 2013-12
• Results First Submitted: 2019-04-03
• Results First Submitted QC: 2019-04-16
• Status Verified: 2019-05
• Results First Posted: 2019-05-08
• Last Update Submitted: 2019-05-09
• Last Update Posted: 2019-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 95

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
White subjects	Acetaminophen	2 x 500 mg acetaminophen by mouth once
Black subjects	Acetaminophen	2 x 500 mg acetaminophen by mouth once

Primary Outcome Measures

Name	Time	Method
Acetaminophen Plasma Clearance Association With Race/Ethnicity	2 days	Plasma total clearance of acetaminophen in plasma measured by HPLC
Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity	2 days	Acetaminophen glucuronidation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity	2 days	Acetaminophen sulfation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity	2 days	Acetaminophen oxidation partial clearance determined from plasma clearance and urinary metabolite excretion
Acetaminophen Plasma Clearance Association With UGT2B15 Genotype	2 days	The association of UGT2B15 genotype with acetaminophen total clearance
Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype	2 days	The association of acetaminophen glucuronidation partial clearance with UGT2B15 genotype
APAP Plasma Adduct Association With UGT2B15 Genotype	2 days	The association of UGT2B15 genotype with APAP plasma adduct concentrations

Trial Locations

Locations (1)

Tufts Clinical Pharmacology Study Unit; 🇺🇸 Boston, Massachusetts, United States