Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

The recruitment status of this study is unknown because the information has not been verified recently.

Verified October 2008 by Tufts University.
Recruitment status was Recruiting

Sponsor:

Collaborator:

National Institute of General Medical Sciences (NIGMS)

Information provided by:

Tufts University

ClinicalTrials.gov Identifier:

NCT00768716

First received: October 7, 2008

Last updated: NA

Last verified: October 2008

History: No changes posted

Purpose

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	Intervention	Phase
Pain Fever Hepatotoxicity	Drug: Acetaminophen	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics

Resource links provided by NLM:

MedlinePlus related topics: Fever

Drug Information available for: Acetaminophen

U.S. FDA Resources

Further study details as provided by Tufts University:

Primary Outcome Measures:

Acetaminophen plasma levels [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Acetaminophen metabolite levels [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	September 2008
Estimated Study Completion Date:	April 2011
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: White subjects	Drug: Acetaminophen 2 x 500 mg oral once
Experimental: Black subjects	Drug: Acetaminophen 2 x 500 mg oral once

Eligibility

Ages Eligible for Study:	18 Years to 64 Years
Genders Eligible for Study:	Both
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768716

Contacts

Contact: Gina Masse

617-636-2192

gina.masse@tufts.edu

Locations

United States, Massachusetts
Tufts Clinical Pharmacology Study Unit	Recruiting
Boston, Massachusetts, United States, 02111
Contact: Gina Masse 617-636-2192

Sponsors and Collaborators

Tufts University

National Institute of General Medical Sciences (NIGMS)

Investigators

Principal Investigator:

Michael H Court, BVSc, PhD

Tufts University

More Information

Publications:

Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: I. Identification of polymorphisms in the 5'-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther. 2005 Jun;313(3):1331-9. Epub 2005 Mar 10.

Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. Epub 2005 Mar 10.

Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther. 2001 Dec;299(3):998-1006.

Responsible Party:	Dr Michael H. Court, Tufts University
ClinicalTrials.gov Identifier:	NCT00768716 History of Changes
Other Study ID Numbers:	8600, GM061834
Study First Received:	October 7, 2008
Last Updated:	October 7, 2008
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Acetaminophen
Antipyretics
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics, Non-Narcotic

Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013

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