Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

ID: NCT00768716
Status: Completed
Phase: Phase 4
Start Date: December 01, 2008
First Submitted: October 07, 2008
Last Updated: February 05, 2018
Results: N/A
Organization: Tufts University
Sponsors & Collaborators: Tufts University, National Institute of General Medical Sciences (NIGMS)
Location: United States
Conditions: Pain, Fever, Hepatotoxicity
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Study Description

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

Condition or disease Intervention/treatment Phase

Fever

Hepatotoxicity

Pain

Drug: Acetaminophen
Other Names
Tylenol
Phase 4

Tracking Information

First Submitted DateOctober 07, 2008
Last Update Posted DateFebruary 05, 2018
Actual Start DateDecember 01, 2008
Actual Completion DateDecember 01, 2013
Actual Primary Completion DateJune 01, 2012
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Acetaminophen plasma levels [Time Frame: 2 days]

    Concentrations of acetaminophen in plasma measured by HPLC

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Acetaminophen plasma metabolite levels [Time Frame: 2 days]

    Concentrations of acetaminophen glucuronide and sulfate in plasma measured by HPLC

  • Acetaminophen urine metabolite levels [Time Frame: 2 days]

    Concentrations of acetaminophen glucuronide, sulfate, cysteine, glutathione, mercapturate in urine measured by HPLC

  • Genetic polymorphisms [Time Frame: 2 days]

    CYP, UGT, and SULT gene polymorphisms assayed using patient DNA

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEffect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
Official TitleEffect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
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

Study TypeInterventional
Study PhasePhase 4
Estimated Enrollment
148
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Basic Science
Conditions
Fever
Hepatotoxicity
Pain
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Acetaminophen

2 x 500 mg by mouth once

Other Names
Tylenol
Study Groups/Cohorts
White subjects
2 x 500 mg acetaminophen by mouth once

Black subjects
2 x 500 mg acetaminophen by mouth once

Study Arms
Experimental Black subjects
2 x 500 mg acetaminophen by mouth once
Drug : Acetaminophen
2 x 500 mg by mouth once

Experimental White subjects
2 x 500 mg acetaminophen by mouth once
Drug : Acetaminophen
2 x 500 mg by mouth once

Arm Intervention/Treatment
Experimental Black subjects
2 x 500 mg acetaminophen by mouth once
Drug : Acetaminophen
Experimental White subjects
2 x 500 mg acetaminophen by mouth once
Drug : Acetaminophen

Recruitment Information

Recruitment Status:Completed
Enrollment148
Completion DateDecember 01, 2013
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
GenderAll
Age18 Years to 64 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT00768716
Other Study ID Numbers
8600
R01GM061834
R01GM102130
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Tufts University
Collaborators
National Institute of General Medical Sciences (NIGMS)
Investigators
Principal Investigator
Michael H Court, BVSc, PhD
Tufts University

Publications