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

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) 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

MedlinePlus related topics: AIDS

Drug Information available for: Methadone Methadone hydrochloride Zidovudine

U.S. FDA Resources

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

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

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.

Study ID Numbers:	ACTG 262
Study First Received:	November 2, 1999
Last Updated:	July 11, 2008
ClinicalTrials.gov Identifier:	NCT00000800
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

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Immunologic Deficiency Syndromes
Virus Diseases
Naphazoline
Methadone

Oxymetazoline
Guaifenesin
HIV Infections
Phenylephrine
Sexually Transmitted Diseases
Phenylpropanolamine
Retroviridae Infections

Additional relevant MeSH terms:

Antimetabolites
Respiratory System Agents
Anti-Infective Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Sensory System Agents
Therapeutic Uses
Analgesics
Analgesics, Opioid

Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Central Nervous System Depressants
Narcotics
Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions
Lentivirus Infections
Peripheral Nervous System Agents
Antitussive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 13, 2009