CYP2B6 Polymorphisms in Methadone Disposition

Not Applicable

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: IV racemic methadone HCl; Drug: Oral racemic methadone HCl

• Registration Number: NCT01648283
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2012-06-06
• Study First Submitted QC: 2012-07-23
• Study First Posted: 2012-07-24
• Study Start: 2012-11
• Primary Completion: 2015-03
• Study Completion: 2015-06
• Results First Submitted: 2018-02-07
• Status Verified: 2018-06
• Results First Submitted QC: 2018-06-18
• Last Update Submitted: 2018-06-18
• Results First Posted: 2018-06-20
• Last Update Posted: 2018-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

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

Read More

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)

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Methadone arm	IV racemic methadone HCl	1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)
Methadone arm	Oral racemic methadone HCl	1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)

Primary Outcome Measures

Name	Time	Method
Methadone Metabolism	up to 96 hours	Plasma metabolite EDDP/methadone area under the concentration-time curve (AUC0-96) ratio

Trial Locations

Locations (1)

Washington University Schoool of Medicine; 🇺🇸 Saint Louis, Missouri, United States