CYP2B6 Polymorphisms in Methadone Disposition

June 18, 2018 updated by: Washington University School of Medicine

Role of CYP2B6 Polymorphisms in Methadone Metabolism and Clearance

This research study will determine if genetic variation in CYP2B6 affects how the body metabolizes methadone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This investigation determined the influence of CYP2B6 genetic variation, specifically CYP2B6*6 polymorphism, on clinical methadone plasma concentrations, clearance, and metabolism. The hypothesis was that CYP2B6*6 heterozygotes or homozygotes would have reduced metabolism and clearance. A secondary objective was to evaluate other less common genotypic variants, when encountered. Healthy volunteers in genotype cohorts CYP2B6*1/*1, CYP2B6*1/*6 , and CYP2B6*6/*6, and also CYP2B6*4 and CYP2B6*5 carriers, received single doses of IV and oral methadone. Plasma and urine methadone and metabolite concentrations were determined by tandem mass spectrometry. The primary outcome measure was methadone metabolism, measured as plasma metabolite/patent area under the concentration-time curve ratio and metabolite formation clearance.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Not Applicable

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
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University Schoool of Medicine

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 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Each subject must meet all of the following criteria:

  • 18-50 yr old
  • CYP2B6*1/*1, CYP2B6*1/*6 or CYP2B6*6/*6 genotype
  • Good general health with no remarkable medical conditions
  • BMI < 33
  • Provided informed consent

Exclusion Criteria:

Subjects will not be enrolled if any of the following criteria exist:

  • Known history of liver or kidney disease
  • Use of prescription or non prescription medications, herbals or foods known to be metabolized by or affect CYP2B6
  • Females who are pregnant or nursing
  • Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction)
  • Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential)

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: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methadone arm
  1. Intravenous racemic methadone HCl, 6.0 mg bolus
  2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)
Drug: IV racemic methadone HCl
IV racemic Methadone HC1 6 mg
Drug: Oral racemic methadone HCl
oral d5-methadone HCl 11 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Methadone Metabolism
Time Frame: up to 96 hours
Plasma metabolite EDDP/methadone area under the concentration-time curve (AUC0-96) ratio
up to 96 hours

Collaborators and Investigators

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

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Evan Kharasch, MD, PhD, Washington University School of Medicine

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)

November 1, 2012

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

June 6, 2012

First Submitted That Met QC Criteria

July 23, 2012

First Posted (Estimate)

July 24, 2012

Study Record Updates

Last Update Posted (Actual)

June 20, 2018

Last Update Submitted That Met QC Criteria

June 18, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201203105

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Publication
    Information comments: Study results published Anesthesiology. 2015 Nov;123(5):1142-53. doi: 10.1097/ALN.0000000000000867

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.

Clinical Trials on Healthy Volunteers

Clinical Trials on IV racemic methadone HCl

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cameroon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe