Safety and Tolerance of Zidovudine With Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks

NCT ID: NCT00000670

Last Updated: 2021-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1989-07-31

Brief Summary

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.

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.

Conditions

HIV Infections

Keywords

Probenecid; Drug Evaluation; Drug Interactions; Acquired Immunodeficiency Syndrome; Zidovudine

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Probenecid

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

BG Petty

Role: STUDY_CHAIR

DM Kornhauser

Role: STUDY_CHAIR

PS Lietman

Role: STUDY_CHAIR

JG Bartlett

Role: STUDY_CHAIR

Locations

UCD Med Ctr

Sacramento, California, United States

Johns Hopkins Hosp

Baltimore, Maryland, United States

Countries

United States

References

Wong SL, Hedaya MA, Sawchuk RJ. Competitive inhibition of zidovudine clearance by probenecid during continuous coadministration. Pharm Res. 1992 Feb;9(2):228-35. doi: 10.1023/a:1018993524818.

Reference Type: BACKGROUND

PMID: 1553347 (View on PubMed)

Other Identifiers

11082

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 107

Identifier Type: -

Identifier Source: org_study_id