Substance-Related Disorders | Role of CYP2B6, CYP3A4, and MDR1 in the Metabolic Clearance of Methadone

Substance-Related Disorders research study

What is the primary objective of this study?

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

Who is eligible to participate?

Inclusion Criteria: - Healthy - Within 25% of ideal body weight Exclusion Criteria: - Pregnant - A prisoner - Enemy, non-combatant - Smoker - Have a history of liver disease - Have a history of heart disease - Have a history of drug abuse - Currently on prescription medication

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Substance-Related Disorders

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:midazolam(drug), digoxin (drug)Midazolam (2mg po) and digoxin (0.5mg po) will be administered one time, an hour apart. Blood concentration will be collected at various points in an 8 hour period.

Drug:Bupropion (drug)Bupropion (150mg po) will be administered one time on a separate visit. Blood concentrations will be collected at various points in a 72 hour period.

Drug:Methadone (drug)Methadone (10mg po) will be administered at a separate visit 2 weeks after the bupropion visit. The dose is given once. Blood concentrations will be measured at various points in a 72 hour period. Pupil constriction will be measured and urine will be collected during this period as well.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Study Status

Unknown status

Start Date: July 2007

Completed Date: January 2011

Phase: Phase 1

Type: Interventional


Primary Outcome: Explore if there is a correlation between the areas of the concentration curves of probe substrates for CYP3A4 and/or CYP2B6 and Pgp and the area of the concentration curve of methadone.

Secondary Outcome: LC-MS assays will be developed to analyze the plasma content of the probe substrates, methadone and their metabolites. Specifically, midazolam, 1-OH midazolam, bupropion, t-butyl-hydroxy bupropion, digoxin, methadone, and EDDP (a methadone metabolite).

Study sponsors, principal investigator, and references

Principal Investigator: Rheem A Totah, PhD

Lead Sponsor: University of Washington


More information:

Beckett AH, Taylor JF, Casy AF, Hassan MM. The biotransformation of methadone in man: synthesis and identification of a major metabolite. J Pharm Pharmacol. 1968 Oct;20(10):754-62.

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