Clinical trial NCT00001008: A Study of Azidothymidine Plus Methadone in Patients With AIDS and AIDS Related Complex (ARC)
Official title: Pharmacokinetic Study of the Interaction of Azidothymidine and Methadone in Patients With AIDS and ARC
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Substance Withdrawal Syndrome
Methadone
Opioid-Related Disorders
Drug Evaluation
Drug Interactions
Drug Therapy, Combination
Administration, Oral
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine if methadone treatment will affect the blood levels of zidovudine (AZT) in patients with AIDS or AIDS-related complex (ARC) who are receiving oral AZT and methadone therapy. In addition, the blood levels of methadone both before and during AZT treatment will be studied, and patients receiving daily oral methadone treatment will be evaluated for signs of narcotic withdrawal during treatment with AZT.

The number of deaths due to AIDS in high-risk populations continues to increase. Nationwide approximately 25 percent of AIDS patients are intravenous (IV) drug abusers, and it is very likely that an increasingly larger number of AIDS patients receiving AZT therapy will have had a history of IV drug abuse. The major chemical treatment for IV drug abuse is daily methadone maintenance therapy, and IV drug abusers who are HIV positive represent a large number of patients who will undergo long-term treatment with both methadone and AZT. Therefore, the study of potential drug interactions is essential.

Detailed description: The number of deaths due to AIDS in high-risk populations continues to increase. Nationwide approximately 25 percent of AIDS patients are intravenous (IV) drug abusers, and it is very likely that an increasingly larger number of AIDS patients receiving AZT therapy will have had a history of IV drug abuse. The major chemical treatment for IV drug abuse is daily methadone maintenance therapy, and IV drug abusers who are HIV positive represent a large number of patients who will undergo long-term treatment with both methadone and AZT. Therefore, the study of potential drug interactions is essential.

The 18 patients are patients with AIDS or ARC. Nine are control patients who are not receiving methadone and are not IV drug abusers. Nine are former IV drug abusers who have been maintained on methadone for at least 6 months and who have been receiving a constant daily dose of methadone for at least 1 month. Plasma and urine levels of methadone are determined over a 4 hour period. The dose of AZT: For the pharmacokinetic study of AZT, plasma and urine samples are taken after oral dose of AZT and an intravenous dose of AZT in the control and methadone groups.

Eligibility criteria: Inclusion Criteria

Prior Medication:

Allowed:

* Oral nonabsorbable antifungal agents.

The study will include 18 patients with AIDS or HIV-related symptomatic illness as defined by the CDC classification group IVa and c2. Of these, 9 methadone recipients will have been maintained on methadone for at least 1 month and will have received a constant daily dose of 30-90 mg of methadone for at least 10 days.

Nine patients will be former intravenous drug abusers.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Temperature \> 101 degrees F.
* Ascites.
* Active opportunistic infection.

Concurrent Medication:

Excluded:

* Other inducers or inhibitors of hepatic microsomal enzymes.
* Any chronic systemic medications.

Patients with the following symptoms or conditions are excluded:

* Temperature \> 101 degrees F.
* Ascites.
* Active opportunistic infection.

Prior Medication:

Excluded within 72 hours of study entry:

* All medication except oral nonabsorbable antifungal agents.
* Excluded within 2 weeks of study entry:
* Any other experimental drug.
* Drugs with known nephrotoxic potential or drugs known to cause neutropenia.
* Rifampin or its derivatives, phenytoin, or barbiturates.

Active drug or alcohol abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Med Ctr / Bronx Municipal Hosp
state: New York
Study officials:
name: G Friedland
role: STUDY_CHAIR
References:
citation: Schwartz EL, Brechbuhl AB, Kahl P, Miller MH, Selwyn PA, Friedland GH. Altered pharmacokinetics of zidovudine in former IV drug-using patients receiving methadone. Int Conf AIDS. 1990 Jun 20-23;6(3):194 (abstract no SB432)
citation: Schwartz EL, Brechbuhl AB, Kahl P, Miller MA, Selwyn PA, Friedland GH. Pharmacokinetic interactions of zidovudine and methadone in intravenous drug-using patients with HIV infection. J Acquir Immune Defic Syndr (1988). 1992;5(6):619-26.