VALPROIC ACID INCREASES CEREBROSPINAL-FLUID ZIDOVUDINE LEVELS IN A PATIENT WITH AIDS

Valproic acid is an anticonvulsant drug known to inhibit the glucuroni dation of zidovudine (AZT) in human liver microsomes. Zidovudine is me tabolized by glucuronidation to the inactive 5'-glucuronide with a sho rt plasma half-life (1.0 +/- 0.2 hour), This case presentation confirm s that valproic acid inhibits glucuronidation in vivo, and this is the first documented observation of increased cerebrospinal fluid levels of zidovudine because of an interaction with valproic acid in a patien t with acquired immune deficiency syndrome (AIDS), The peak plasma AZT level for the control period was 119 ng/mL, which increased almost 3- fold to 344 ng/mL with valproic acid (1.5 g/day), The plasma AZT troug h was 47 ng/mL, which also increased almost 3-fold to 124 ng/mL with v alproic acid, The molar ratio of plasma 5'-glucuronide/AZT at the peak was reduced from 1.77 (control) to 1.07 with valproic acid, The 5'-gl ucuronide/AZT ratio at the trough was reduced markedly from 5.0 (contr ol) to 0.93 with valproic acid, suggesting in vivo inhibition of glucu ronidation, Cerebrospinal AZT levels, drawn 30 minutes after peak plas ma levels, increased from 27 ng/mL for the control to 47 ng/mL with va lproic acid, which paralleled the change in peak plasma concentrations , This interaction with valproic acid may contribute to higher AZT lev els in the brains of patients with human immunodeficiency virus-relate d (HIV) encephalopathy.