Methadone Effects on Zidovudine (ZDV, AZT) Disposition
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Methadone hydrochloride (Drug); Zidovudine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Jatlow P, Study Chair
Rainey P, Study Chair
Summary
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.
Clinical Details
Official title: Methadone Effects on Zidovudine (ZDV, AZT) Disposition
Study design: Masking: Open Label, Primary Purpose: 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Yale Univ / New Haven, New Haven, Connecticut 065102483, United States
Additional Information
Click here for more information about Zidovudine
Related publications: Jatlow P, Mccance EF, Rainey PM, Trapnell CB, Friedland G. Methadone increases zidovudine exposure in HIV-infected injection drug users (ACTG 262). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:129 McCance-Katz EF, Rainey PM, Jatlow P, Friedland G. Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262). J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 15;18(5):435-43.
Last updated: March 15, 2012
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