CYP2B6 Polymorphisms in Methadone Disposition

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

Detailed Description
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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.

Official Title
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Role of CYP2B6 Polymorphisms in Methadone Metabolism and Clearance

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: IV racemic methadone HCl
* Drug: Oral racemic methadone HCl


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methadone polymorphisms