Conditions: Healthy Volunteers
Keywords: methadone polymorphisms
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 78
Healthy volunteers: yes

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.

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

Interventions: intervention 1: IV racemic methadone HCl intervention 2: Oral racemic methadone HCl
Intervention descriptions: intervention 1: IV racemic Methadone HC1 6 mg intervention 2: oral d5-methadone HCl 11 mg

Protocol document: