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Safety and Tolerance of Zidovudine with Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks - Article


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Zidovudine Injection

Azidothymidine Injection; AZT Injection; Compound S; Retrovir Injection


Clinical Trial: Safety and Tolerance of Zidovudine with Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks

This study has been completed.

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

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 Treatment or Intervention
HIV Infections
 Drug: Probenecid
 Drug: Zidovudine

MedlinePlus related topics:  AIDS

Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study

Further Study Details: 

Expected Total Enrollment:  16

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 above,  Genders Eligible for Study:  Both

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.

Location Information


California
      UCD Med Ctr, Sacramento,  California,  95817,  United States

Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States

Study chairs or principal investigators

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

More Information

Click here for more information about Zidovudine

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
Record last reviewed:  August 1991
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000670
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005


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October 10, 2008



Page Updated: June 1, 2005
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