Role of CYP2B6, CYP3A4, & MDR1 in the Metabolic Clearance of Methadone

Status Recruiting

Clinical Trial Summary

The purpose of this study is to determine to what extent CYP2B6, CYP3A4, and MDR1 polymorphisms affect the metabolism of methadone.

Clinical Trial Description

Methadone maintenance treatment (MMT) has been used to rehabilitate the opiate addict resulting in a higher quality of life for the patient as well as improving social and psychological functioning while reducing the overall cost to society. The maintenance dose of methadone is highly variable between patients, and drug-drug interactions have been observed between methadone and various medications used to treat a variety of diseases. Identification and understanding of the enzymes responsible for the metabolism of methadone could potentially lead to improved strategy in individualizing methadone dosing and reduce the risk of adverse drug interactions.

Several cytochrome P450 enzymes (CYPs) have been identified and hypothesized to be involved in methadone metabolism in vitro, particularly CYP2B6 and CYP3A4. However, the quantitative contribution of CYP2B6 and CYP3A4 in the elimination clearance of methadone in vivo remains undefined. In addition, methadone is a substrate of the efflux transporter, P-glycoprotein (Pgp) at the intestinal mucosa. We are proposing a pilot study in healthy human subjects to investigate the following hypotheses:

1. Pgp limits the gastrointestinal absorption

2. Inter-subject variations in CYP2B6 and CYP3A4 activities explain the variation in methadone clearance in vivo

This will be accomplished by correlating the pharmacokinetics of methadone and the phenotype probes for Pgp (digoxin), CYP2B6 (bupropion) and CYP3A4 (midazolam). We plan to use these data to design a human subject study to assess the utility of MDR1 and CYP genotyping in predicting the methadone maintenance dose in a cohort of MMT patients. ;

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

Substance-Related Disorders

Clinical Trial Details

NCT number	NCT00504413
Study type	Interventional
Source	University of Washington
Contact	Jean C Dinh, PharmD
Phone	206.616.2775
Email	jeandinh@u.washington.edu
Status	Recruiting
Phase	Phase 1
Start date	July 2007
Completion date	January 2011

View Details

See also
Status	Clinical Trial	Phase
Recruiting	`NCT05054738` - CRP and S&A for Inpatient Veterans	N/A
Recruiting	`NCT04157062` - An Open-Label Trial of Repetitive Transcranial Magnetic Stimulation for Opioid Use Disorder	N/A
Completed	`NCT02233738` - Group Motivational Interviewing (GMI) For Homeless Veterans In VA Services	N/A
Enrolling by invitation	`NCT06084221` - Fatal Overdose Review Teams - Research to Enhance Surveillance Systems	N/A
Completed	`NCT02907944` - Working With HIV Clinics to Adopt Addiction Treatments Using Implementation Facilitation	N/A
Completed	`NCT02570360` - Exercise and Treatment-as-usual in Substance Use Treatment Outcomes	N/A
Completed	`NCT02829970` - Helping College Students With ADHD Lead Healthier Lifestyles	N/A
Completed	`NCT02715557` - Arise: An Online Relapse Prevention Tool for Adolescent Substance Abusers	N/A
Completed	`NCT02125539` - Field Trial of a Relapse Prevention Program for Adolescents Receiving Substance Use Treatment	Phase 2
Completed	`NCT02945371` - Tailored Inhibitory Control Training to Reverse EA-linked Deficits in Mid-life	N/A
Completed	`NCT02388243` - The Computer-based Drug and Alcohol Training Assessment in Kenya	N/A
Completed	`NCT02218970` - The Effect of Muscular Strength Training in Patients With Drug Addiction	N/A
Completed	`NCT01633138` - Performance-based Reinforcement to Enhance Cognitive Remediation Therapy	N/A
Completed	`NCT01591239` - Home-Based Program to Help Parents of Drug Abusing Adolescents	N/A
Active, not recruiting	`NCT01539525` - Screening to Augment Referral to Treatment- Project START	Phase 2
Withdrawn	`NCT01224002` - A Comparative Feasibility Study to Assess the Prevalence and Severity of Dental Caries in Incarcerated People Who Abuse Methamphetamine	N/A
Withdrawn	`NCT00891631` - Primary Care iSBIRT to Reduce Serious Teen Health Risks	Phase 1/Phase 2
Completed	`NCT00970372` - Dual-Diagnosis and Compulsory Treatment	N/A
Completed	`NCT01365247` - Concurrent Treatment for Substance Dependent Individuals With Post-Traumatic Stress Disorder (PTSD)	N/A
Completed	`NCT00419029` - Motivational Interviewing to Engage Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) Veterans in Mental Health Treatment	N/A

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Role of CYP2B6, CYP3A4, and MDR1 in the Metabolic Clearance of Methadone

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms