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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

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 ...

Gender

MALE

Eligibility 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.

Trial Officials