The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.
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.
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 Design
Endpoint Classification: Pharmacokinetics Study, Masking: Open Label, Primary Purpose: Treatment
Conditions
HIV Infections
Intervention
Valproic acid, Zidovudine
Location
Tulane Univ Med School
New Orleans
Louisiana
United States
701122699
Status
Completed
Source
National Institute of Allergy and Infectious Diseases (NIAID)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00000629
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Valproic Acid
A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.
Encephalitis, Viral
Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.
Meningitis, Viral
Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RHABDOVIRIDAE INFECTIONS; ARENAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; JC VIRUS infections; and RETROVIRIDAE INFECTIONS may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, PHOTOPHOBIA, and signs of meningeal irritation. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
Paramyxoviridae Infections
Infections with viruses of the family PARAMYXOVIRIDAE. This includes MORBILLIVIRUS INFECTIONS; RESPIROVIRUS INFECTIONS; PNEUMOVIRUS INFECTIONS; HENIPAVIRUS INFECTIONS; AVULAVIRUS INFECTIONS; and RUBULAVIRUS INFECTIONS.
Central Nervous System Infections
Pathogenic infections of the brain, spinal cord, and meninges. DNA VIRUS INFECTIONS; RNA VIRUS INFECTIONS; BACTERIAL INFECTIONS; MYCOPLASMA INFECTIONS; SPIROCHAETALES INFECTIONS; fungal infections; PROTOZOAN INFECTIONS; HELMINTHIASIS; and PRION DISEASES may involve the central nervous system as a primary or secondary process.
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