CYP2B6 Polymorphisms in Methadone Disposition

The Washington University

Status: Completed

Conditions: Healthy Volunteers

Treatments: Drug: Oral racemic methadone HCl; Drug: IV racemic methadone HCl

Study type: Interventional

Funder types: Other

Identifiers

NCT01648283

201203105

Details and patient eligibility

About

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

Full 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.

Enrollment: 78 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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78 participants in 1 patient group

Methadone arm

Experimental group

Description:

1. Intravenous racemic methadone HCl, 6.0 mg bolus 2. Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)

Treatment:

Drug: Oral racemic methadone HCl

Drug: IV racemic methadone HCl