Safety and Tolerance of Zidovudine With Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000670

Purpose

To evaluate the interaction of probenecid with zidovudine (AZT). Because AZT is eliminated quickly from the body, it must be taken frequently. A previous study showed that probenecid slowed the elimination of AZT without side effects, but that study lasted only 5 days. This study is to see whether this effect continues for 1 month and whether the continuation of probenecid and AZT is free of side effects over 1 month.

Condition	Intervention
HIV Infections	Drug: Probenecid Drug: Zidovudine

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine Probenecid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Pharmacokinetics Study
Official Title:	Safety and Tolerance of Zidovudine With Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks

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

Estimated Enrollment:

16

Detailed Description:

Because AZT is eliminated quickly from the body, it must be taken frequently. A previous study showed that probenecid slowed the elimination of AZT without side effects, but that study lasted only 5 days. This study is to see whether this effect continues for 1 month and whether the continuation of probenecid and AZT is free of side effects over 1 month.

Patients are hospitalized overnight on three separate occasions. On the first admission, AZT is administered every 4 hours. On the second day, 15 blood samples are taken to determine how fast the AZT enters and is removed from the bloodstream (pharmacokinetics). On the second day, after all the blood specimens have been collected, patient starts taking probenecid by mouth every 8 hours, and is discharged from the research unit. The AZT dose is then taken every 8 hours. One week later and again 3 weeks after that, patient is readmitted overnight and the blood sampling to measure AZT levels is repeated. AMENDED: 8 additional patients will be enrolled using the same doses of AZT but a lower dose of probenecid.

Eligibility

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

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

Interferon.
Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.

Concurrent Treatment:

Allowed:

Radiation for skin lesions.

Patients with symptomatic HIV infection taking zidovudine (AZT) five or six times a day as therapy. Includes patients with AIDS who have history of cytologically confirmed Pneumocystis carinii pneumonia (PCP), patients with advanced AIDS related complex (ARC), and HIV antibody positive patients.

Patients must be able to give written informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

Allergy to probenecid.
Any underlying medical condition sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy.
History of urinary tract urate stones or gout.
Becoming acutely ill, unstable, or febrile.

Concurrent Medication:

Excluded:

Methotrexate.
Antiretroviral drugs.
Ganciclovir.
Amphotericin.
Experimental drugs.
Isoniazid.
Pyrazinamide.
Flucytosine.
Intravenous pentamidine.
Dapsone.
Fansidar.
Antineoplastic drugs not specifically allowed.
Trimethoprim / sulfamethoxazole.
Valproic acid.
Opiates.
Rifampin.
Sulfonylureas.

Concurrent Treatment:

Excluded:

Radiation not specifically allowed.

Patients with the following are excluded:

Allergy to probenecid.
Any underlying medical condition sufficient, in investigator's opinion, to prevent adequate compliance with study therapy.
History of urinary tract urate stones or gout.
Becoming acutely ill, unstable, or febrile.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000670

Locations

United States, California
UCD Med Ctr
Sacramento, California, United States, 95817
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	BG Petty
Study Chair:	DM Kornhauser
Study Chair:	PS Lietman
Study Chair:	JG Bartlett

More Information

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

Publications:

Wong SL, Hedaya MA, Sawchuk RJ. Competitive inhibition of zidovudine clearance by probenecid during continuous coadministration. Pharm Res. 1992 Feb;9(2):228-35.

Study ID Numbers:	ACTG 107
Study First Received:	November 2, 1999
Last Updated:	August 19, 2008
ClinicalTrials.gov Identifier:	NCT00000670
Health Authority:	United States: Federal Government

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

Probenecid
Drug Evaluation
Drug Interactions
Acquired Immunodeficiency Syndrome
Zidovudine

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome

Probenecid
Zidovudine
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Renal Agents

Antiviral Agents
Gout Suppressants
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Uricosuric Agents
Therapeutic Uses
Lentivirus Infections
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009