The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.

July 29, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Primary objective: To study the pharmacokinetic interaction between zidovudine (AZT) and valproic acid in asymptomatic HIV-infected patients, characterizing AZT's oral bioavailability, plasma elimination half-time, plasma levels, and urinary excretion of AZT, 5'-O-glucuronide (GAZT), and 3'-amino-3'-deoxythymidine (AMT). Secondary objective: To establish the safety of short-term administration of AZT and valproic acid in combination with regard to hematologic parameters and liver function in asymptomatic HIV-infected patients.

Preliminary studies using human liver tissue have shown that valproic acid inhibits the metabolic inactivation of zidovudine (AZT), which may prolong the plasma half-life of AZT and thus prolong the duration of the drug's effects in the body.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Preliminary studies using human liver tissue have shown that valproic acid inhibits the metabolic inactivation of zidovudine (AZT), which may prolong the plasma half-life of AZT and thus prolong the duration of the drug's effects in the body.

Six asymptomatic HIV-infected patients are treated with AZT orally every 8 hours on days 1 through 4, then with a single dose on day 5 (after 8 hours of fasting), followed by pharmacokinetic sampling. On days 6 through 9, patients receive AZT orally every 8 hours in combination with valproic acid (lowest dose in the first 5 patients and a higher dose in patients 6 and 7) orally every 8 hours. On day 10, AZT and 1 of the 2 doses of valproic acid are given orally as single doses, followed by pharmacokinetic sampling. AZT is continued alone orally every 8 hours on days 11 through 14, then resumed at the patient's usual dose beginning on day 15. Per 03/09/92 amendment, dosing schedule may be modified slightly to accommodate patients with scheduling conflicts.

Study Type

Interventional

Enrollment

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Louisiana
      • New Orleans, Louisiana, United States, 701122699
        • Tulane Univ Med School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

Vitamins if already being taken prior to start of therapy.

Patients must have:

  • Asymptomatic HIV infection.
  • CD4 count between 300 and 650.

Prior Medication:

Required:

  • AZT at doses between 500 and 1200 mg/day for at least 6 weeks prior to enrollment.

Allowed:

  • Aspirin, Tylenol, or ibuprofen up to 48 hours prior to start of therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Positive Hepatitis B surface antigen or clinical evidence of chronic active hepatitis of any type.
  • Signs or symptoms of HIV infection including oral candidiasis, history of multidermatomal zoster, unexplained weight loss in excess of 10 percent body weight in the past 6 months, chronic diarrhea, or history of AIDS-defining opportunistic infections.

Concurrent Medication:

Excluded:

  • Concomitant medications (other than AZT) for the 14 days prior to start of therapy.

Patients with the following prior conditions are excluded:

  • History of AZT intolerance including hematologic, hepatic, and/or neurologic toxicity.
  • History of seizures.
  • History of any antiepileptics within the past 10 years.
  • History of abnormal bleeding or intrinsic or extrinsic coagulopathy.
  • Signs or symptoms of HIV infection including oral candidiasis, history of multidermatomal zoster, unexplained weight loss in excess of 10 percent body weight in the past 6 months, chronic diarrhea, or history of AIDS-defining opportunistic infections.

Prior Medication:

Excluded:

  • Antiepileptics within the past 10 years.
  • Prior valproic acid.
  • Concomitant medications (other than AZT) within 14 days of enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Lertora JJL

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ESTIMATE)

July 30, 2008

Last Update Submitted That Met QC Criteria

July 29, 2008

Last Verified

October 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 191

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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