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.

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Publications

• Background 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.

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