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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000670
• Other study ID #: ACTG 107
• Secondary ID: 11082
• Status: Completed
• Phase: N/A
• Est. completion date: July 1989

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 1989
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Probenecid

• Zidovudine

Locations

Country	Name	City	State
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	UCD Med Ctr	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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