Role of CYP2B6, CYP3A4, and MDR1 in the Metabolic Clearance of Methadone

NCT00504413 | Unknown Phase 1 DMC

• 2 other identifiers: 30931-A06-3659-A 01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine to what extent CYP2B6, CYP3A4, and MDR1 polymorphisms affect the metabolism of methadone.

Conditions

Substance-Related Disorders

Keywords

Metabolic Networks and Pathways; Methadone; Polymorphism, genetic; Cytochrome P-450 Enzyme System

Outcome Measures

Primary Outcomes (1)

• Explore if there is a correlation between the areas of the concentration curves of probe substrates for CYP3A4 and/or CYP2B6 and Pgp and the area of the concentration curve of methadone.

  two years

Secondary Outcomes (2)

• LC-MS assays will be developed to analyze the plasma content of the probe substrates, methadone and their metabolites. Specifically, midazolam, 1-OH midazolam, bupropion, t-butyl-hydroxy bupropion, digoxin, methadone, and EDDP (a methadone metabolite).

  two years

• Isolate and bank the DNA of the subjects for future genotyping of variant alleles that will be identified in this study to be important in methadone pharmacokinetics.

  two years

Interventions

midazolam(drug), digoxin (drug) DRUG

Midazolam (2mg po) and digoxin (0.5mg po) will be administered one time, an hour apart. Blood concentration will be collected at various points in an 8 hour period.

Bupropion (drug) DRUG

Bupropion (150mg po) will be administered one time on a separate visit. Blood concentrations will be collected at various points in a 72 hour period.

Also known as: Wellbutrin

Methadone (drug) DRUG

Methadone (10mg po) will be administered at a separate visit 2 weeks after the bupropion visit. The dose is given once. Blood concentrations will be measured at various points in a 72 hour period. Pupil constriction will be measured and urine will be collected during this period as well.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy
• Within 25% of ideal body weight

You may not qualify if:

• Pregnant
• A prisoner
• Enemy, non-combatant
• Smoker
• Have a history of liver disease
• Have a history of heart disease
• Have a history of drug abuse
• Currently on prescription medication

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

University of Washington General Clinical Research Center

Seattle, Washington, 98105, United States

RECRUITING

Related Publications (63)

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  BACKGROUND

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Digoxin; Pharmaceutical Preparations; Bupropion; Methadone

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Propiophenones; Ketones; Organic Chemicals

Study Officials

• Rheem A Totah, PhD

  University of Washington, Medicinal Chemistry Department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean C Dinh, PharmD

CONTACT

206.616.2775; jeandinh@u.washington.edu

Rheem A Totah, PhD

CONTACT

206.543.9481; rtotah@u.washington.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 18, 2007
• First Posted: July 20, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: October 13, 2010

Record last verified: 2010-10

Locations

US (1)