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Sponsored by: |
University of Washington |
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Information provided by: | University of Washington |
ClinicalTrials.gov Identifier: | NCT00504413 |
The purpose of this study is to determine to what extent CYP2B6, CYP3A4, and MDR1 polymorphisms affect the metabolism of methadone.
Condition | Intervention | Phase |
---|---|---|
Substance-Related Disorders |
Drug: midazolam(drug), digoxin (drug) Drug: Bupropion (drug) Drug: Methadone (drug) |
Phase I |
Study Type: | Interventional |
Study Design: | Basic Science, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study |
Official Title: | Role of CYP2B6, CYP3A4, and MDR1 in the Metabolic Clearance of Methadone in Human Subjects |
Estimated Enrollment: | 20 |
Study Start Date: | July 2007 |
Estimated Study Completion Date: | November 2009 |
Estimated Primary Completion Date: | November 2009 (Final data collection date for primary outcome measure) |
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:
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.
Ages Eligible for Study: | 18 Years to 40 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Jean C Dinh, BS | 206.616.2775 | jeandinh@u.washington.edu |
Contact: Rheem A Totah, PhD | 206.543.9481 | rtotah@u.washington.edu |
United States, Washington | |
University of Washington General Clinical Research Center | Recruiting |
Seattle, Washington, United States, 98105 | |
Principal Investigator: Rheem A Totah, PhD | |
Principal Investigator: Danny Shen, PhD | |
Sub-Investigator: Gregory Terman, MD | |
Sub-Investigator: Kristin K Patton, MD | |
Sub-Investigator: Jean C Dinh, BS |
Principal Investigator: | Rheem A Totah, PhD | University of Washington, Medicinal Chemistry Department |
Responsible Party: | University of Washington ( Rheem Totah/Assistant Professor, Medicinal Chemistry ) |
Study ID Numbers: | 30931-A, 06-3659-A 01 |
Study First Received: | July 18, 2007 |
Last Updated: | August 20, 2009 |
ClinicalTrials.gov Identifier: | NCT00504413 History of Changes |
Health Authority: | United States: Institutional Review Board |
Metabolic Networks and Pathways Methadone Polymorphism, genetic Cytochrome P-450 Enzyme System |
Dopamine Uptake Inhibitors Neurotransmitter Agents Psychotropic Drugs Anesthetics Disorders of Environmental Origin Naphazoline Dopamine Mental Disorders Hypnotics and Sedatives Substance-Related Disorders Digoxin Phenylpropanolamine Analgesics Antidepressive Agents, Second-Generation Analgesics, Opioid |
Antidepressive Agents Anesthetics, Intravenous Tranquilizing Agents Adjuvants, Immunologic Central Nervous System Depressants Narcotics Midazolam Methadone Anesthetics, General Guaifenesin Bupropion Dopamine Agents Anti-Anxiety Agents Peripheral Nervous System Agents |
Dopamine Uptake Inhibitors Respiratory System Agents Neurotransmitter Uptake Inhibitors Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action GABA Modulators Physiological Effects of Drugs Psychotropic Drugs Disorders of Environmental Origin Anesthetics Sensory System Agents Mental Disorders Therapeutic Uses Hypnotics and Sedatives Substance-Related Disorders |
Analgesics Antidepressive Agents, Second-Generation Antidepressive Agents Analgesics, Opioid Anesthetics, Intravenous Tranquilizing Agents Central Nervous System Depressants Narcotics Midazolam Pharmacologic Actions Adjuvants, Anesthesia Methadone Anesthetics, General Bupropion GABA Agents |