Methadone Effects on Zidovudine (ZDV, AZT) Disposition

• Status: Completed
• Trial end date: 1998-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Glaxo Wellcome
• Treatments: Methadone; Zidovudine

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.