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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Valproic Acid; Zidovudine

Criteria

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.