Methadone Effects on Zidovudine (ZDV, AZT) Disposition

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine whether methadone maintenance alters the pharmacokinetics of zidovudine (AZT). To determine whether any such effect of methadone on disposition of AZT is time dependent and whether a metabolic interaction between AZT and methadone exists.

Injection drug users represent an increasing proportion of HIV-infected persons. Since daily methadone maintenance is the major chemical treatment for injection drug abuse, it is important to determine the impact of methadone on AZT absorption, distribution, and elimination.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Injection drug users represent an increasing proportion of HIV-infected persons. Since daily methadone maintenance is the major chemical treatment for injection drug abuse, it is important to determine the impact of methadone on AZT absorption, distribution, and elimination.

After 6 days of inpatient detoxification with clonidine, patients addicted to opiates are randomized to receive either oral or intravenous AZT for the first dose, followed by determination of plasma and urine pharmacokinetics. On the second day of AZT dosing, the alternate form of administration will be used for the first dose. On both days, all other doses are given orally. Patients then begin methadone maintenance in combination with AZT for 7 days of inpatient treatment, with further pharmacokinetic sampling. After hospitalization for 16 days total, patients continue AZT/methadone treatment on an outpatient basis, and then 2 months later are readmitted as inpatients for 5 days for further pharmacokinetic sampling. Control patients who are not addicted to opiates are hospitalized for 3 days at study entry and are randomized for AZT treatment and pharmacokinetic sampling in the same manner as the first group, although they will not receive methadone treatment. Control patients are readmitted for 2 days after 1 week of AZT treatment and then again after 59 days of AZT treatment.

Study Type

Interventional

Enrollment

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 065102483
        • Yale Univ / New Haven

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients must have:

  • Documented HIV infection.
  • CD4 count 100 - 500 cells/mm3.
  • No active opportunistic infection or wasting syndrome.
  • Opiate addiction or prior enrollment in a methadone treatment program (methadone recipients only).
  • Admission to General Clinical Research Center at Yale-New Haven Hospital for clonidine detoxification (methadone recipients only).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Inadequate IV access.
  • Benzodiazepine abuse.

Concurrent Medication:

Excluded:

  • Amiodarone.
  • Anesthetics, general.
  • Azithromycin.
  • Barbiturates.
  • Carbamazepine.
  • Cimetidine.
  • Ciprofloxacin.
  • Clarithromycin.
  • Dexamethasone.
  • Disulfiram.
  • Erythromycin.
  • Fluoroquinolones.
  • Fluoxetine.
  • Gestodene.
  • Hydrochlorothiazide.
  • Hypoglycemics, oral.
  • Isoniazid.
  • Itraconazole.
  • Ketoconazole.
  • Levomepromazine.
  • MAO inhibitors.
  • Methoxsalen.
  • Nafcillin.
  • Narcotic analgesics.
  • Naringenin.
  • Norethindrone.
  • Omeprazole.
  • Pentazocine.
  • Phenothiazines.
  • Phenytoin.
  • Quinidine.
  • Ranitidine.
  • Rifabutin.
  • Rifampin.
  • Sedative Hypnotics.
  • Sulfaphenazole.
  • Tranquilizers (except at discretion of investigator and protocol chair).
  • Tricyclic antidepressants.
  • Troleandomycin.
  • Warfarin.

Prior Medication:

Excluded within 4 weeks prior to study entry:

  • Rifampin or its derivatives.
  • Phenytoin.
  • Barbiturates.
  • Cimetidine.
  • Other drugs known to induce or inhibit hepatic microsomal enzymes.

Excluded within 14 days prior to study entry:

  • Any other experimental drug.
  • Drugs with known nephrotoxic potential.

Excluded within 72 hours prior to study entry:

  • Amiodarone.
  • Anesthetics, general.
  • Azithromycin.
  • Carbamazepine.
  • Ciprofloxacin.
  • Clarithromycin.
  • Dexamethasone.
  • Disulfiram.
  • Erythromycin.
  • Fluoroquinolones.
  • Fluoxetine.
  • Gestodene.
  • Hydrochlorothiazide.
  • Hypoglycemics, oral.
  • Isoniazid.
  • Itraconazole.
  • Ketoconazole.
  • Levomepromazine.
  • MAO inhibitors.
  • Methoxsalen.
  • Nafcillin.
  • Narcotic analgesics.
  • Naringenin.
  • Norethindrone.
  • Omeprazole.
  • Pentazocine.
  • Phenothiazines.
  • Quinidine.
  • Ranitidine.
  • Rifabutin.
  • Sedative Hypnotics.
  • Sulfaphenazole.
  • Tranquilizers (except at discretion of investigator and protocol chair).
  • Tricyclic antidepressants.
  • Troleandomycin.
  • Warfarin.

Continued active drug or alcohol abuse or dependence that would decrease the probability of study completion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Glaxo Wellcome

Investigators

  • Study Chair: Jatlow P
  • Study Chair: Rainey P

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

October 1, 1998

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 262
  • 11239 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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