Role of CYP2B6 Polymorphisms in Methadone Metabolism and Clearance
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 78
- Locations
- 1
- Primary Endpoint
- Methadone Metabolism
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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)
Arms & Interventions
Methadone arm
- Intravenous racemic methadone HCl, 6.0 mg bolus
- Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)
Intervention: IV racemic methadone HCl (Drug)
Methadone arm
- Intravenous racemic methadone HCl, 6.0 mg bolus
- Oral deuterated racemic methadone HCl, 11 mg capsule (IND#58,511)
Intervention: Oral racemic methadone HCl (Drug)
Outcomes
Primary Outcomes
Methadone Metabolism
Time Frame: up to 96 hours
Plasma metabolite EDDP/methadone area under the concentration-time curve (AUC0-96) ratio
Secondary Outcomes
No secondary outcomes reported