Safety and Tolerance of Zidovudine With Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Probenecid (Drug); Zidovudine (Drug)
Phase: N/A
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
BG Petty, Study Chair
DM Kornhauser, Study Chair
PS Lietman, Study Chair
JG Bartlett, Study Chair
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.
Clinical Details
Official title: Safety and Tolerance of Zidovudine With Probenecid and the Effect of Probenecid on Zidovudine Pharmacokinetics Over Four Weeks
Study design: Treatment, Open Label, Pharmacokinetics Study
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): 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.
Locations and Contacts
UCD Med Ctr, Sacramento, California 95817, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Additional Information
Click here for more information about Zidovudine
Related 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.
Last updated: June 23, 2005
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