HIV Infections
Conditions
Keywords
Methadone, Drug Interactions, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine
Brief 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.
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.
Interventions
DRUGZidovudine
Sponsors
Glaxo Wellcome
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Countries
United States
Outcome results
None listed