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Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

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ClinicalTrials.gov Identifier: NCT00768716
Recruitment Status : Completed
First Posted : October 8, 2008
Results First Posted : May 8, 2019
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
National Institute of General Medical Sciences (NIGMS)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Pain Fever Hepatotoxicity Drug: Acetaminophen Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics
Actual Study Start Date : December 2008
Actual Primary Completion Date : June 2012
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: White subjects
2 x 500 mg acetaminophen by mouth once
Drug: Acetaminophen
2 x 500 mg by mouth once
Other Name: Tylenol

Experimental: Black subjects
2 x 500 mg acetaminophen by mouth once
Drug: Acetaminophen
2 x 500 mg by mouth once
Other Name: Tylenol




Primary Outcome Measures :
  1. Acetaminophen Plasma Clearance Association With Race/Ethnicity [ Time Frame: 2 days ]
    Plasma total clearance of acetaminophen in plasma measured by HPLC

  2. Acetaminophen Glucuronidation Partial Clearance Association With Race/Ethnicity [ Time Frame: 2 days ]
    Acetaminophen glucuronidation partial clearance determined from plasma clearance and urinary metabolite excretion

  3. Acetaminophen Sulfation Partial Clearance Association With Race/Ethnicity [ Time Frame: 2 days ]
    Acetaminophen sulfation partial clearance determined from plasma clearance and urinary metabolite excretion

  4. Acetaminophen Oxidation Partial Clearance Association With Race/Ethnicity [ Time Frame: 2 days ]
    Acetaminophen oxidation partial clearance determined from plasma clearance and urinary metabolite excretion

  5. Acetaminophen Plasma Clearance Association With UGT2B15 Genotype [ Time Frame: 2 days ]
    The association of UGT2B15 genotype with acetaminophen total clearance

  6. Acetaminophen Glucuronidation Partial Clearance Association With UGT2B15 Genotype [ Time Frame: 2 days ]
    The association of acetaminophen glucuronidation partial clearance with UGT2B15 genotype

  7. APAP Plasma Adduct Association With UGT2B15 Genotype [ Time Frame: 2 days ]
    The association of UGT2B15 genotype with APAP plasma adduct concentrations



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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00768716


Locations
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United States, Massachusetts
Tufts Clinical Pharmacology Study Unit
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts University
National Institute of General Medical Sciences (NIGMS)
Investigators
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Principal Investigator: Michael H Court, BVSc, PhD Tufts University

Publications of Results:
Other Publications:

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Responsible Party: Tufts University
ClinicalTrials.gov Identifier: NCT00768716     History of Changes
Other Study ID Numbers: 8600
R01GM061834 ( U.S. NIH Grant/Contract )
R01GM102130 ( U.S. NIH Grant/Contract )
First Posted: October 8, 2008    Key Record Dates
Results First Posted: May 8, 2019
Last Update Posted: May 23, 2019
Last Verified: May 2019

Additional relevant MeSH terms:
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Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics