Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

May 9, 2019 updated by: Tufts University
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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

95

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Clinical Pharmacology Study Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: White subjects
2 x 500 mg acetaminophen by mouth once
Drug: Acetaminophen
2 x 500 mg by mouth once
Other Names:
  • Tylenol
Experimental: Black subjects
2 x 500 mg acetaminophen by mouth once
Drug: Acetaminophen
2 x 500 mg by mouth once
Other Names:
  • Tylenol

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tufts University

Collaborators

National Institute of General Medical Sciences (NIGMS)

Investigators

  • Principal Investigator: Michael H Court, BVSc, PhD, Tufts University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2008

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

October 7, 2008

First Submitted That Met QC Criteria

October 7, 2008

First Posted (Estimate)

October 8, 2008

Study Record Updates

Last Update Posted (Actual)

May 23, 2019

Last Update Submitted That Met QC Criteria

May 9, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8600
  • R01GM061834 (U.S. NIH Grant/Contract)
  • R01GM102130 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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