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

NCT00000629 | Completed Phase 1

• 1 other identifier: ACTG 191
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infections

Keywords

Valproic Acid; Zidovudine

Interventions

Valproic acid DRUG

Zidovudine DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Tulane Univ Med School

New Orleans, Louisiana, 701122699, United States

Location

Related Publications (2)

• Lertora J, Akula S, Greenspan D, Rege A, Agrawal K, George W, Hyslop N. Valproic acid inhibits zidovudine glucuronidation in patients with HIV infection. Int Conf AIDS. 1992 Jul 19-24;8(3):100 (abstract no PuB 7307)

  BACKGROUND

• Lertora JJ, Rege AB, Greenspan DL, Akula S, George WJ, Hyslop NE Jr, Agrawal KC. Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 1994 Sep;56(3):272-8. doi: 10.1038/clpt.1994.137.

  PMID: 7924122 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Valproic Acid; Zidovudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Lertora JJL

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Last Updated: July 30, 2008

Record last verified: 2003-10

Locations

US (1)