Methadone Effects on Zidovudine (ZDV, AZT) Disposition - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Glaxo Wellcome
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000800

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Methadone hydrochloride Drug: Zidovudine	Phase I

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	Methadone Effects on Zidovudine (ZDV, AZT) Disposition

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Drug Reactions HIV/AIDS

Drug Information available for: Zidovudine Methadone Methadone hydrochloride

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

15

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000800

Locations

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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Glaxo Wellcome

Investigators

Study Chair:	Jatlow P
Study Chair:	Rainey P

More Information

Additional Information:

Click here for more information about Zidovudine This link exits the ClinicalTrials.gov site

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.

ClinicalTrials.gov Identifier:	NCT00000800 History of Changes
Other Study ID Numbers:	ACTG 262
Study First Received:	November 2, 1999
Last Updated:	July 11, 2008
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Methadone
Drug Interactions
Drug Therapy, Combination

Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Methadone
Zidovudine
Analgesics, Opioid
Analgesics

Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012