Reduced valproate plasma levels possible after introduction of efavirenz in a bipolar patient

The case of a bipolar patient with concomitant multidrug addiction is described who presented a decrease in valproate plasma level of more than 50% shortly after antiretroviral therapy was initiated. Despite important dose augmentations of up to 4 g/day, plasma levels were difficult to raise to the target concentration of 50 mg/dL. The possible mechanisms underlying the observed pharmacokinetic changes are discussed: (i) a uridine diphosphate-glucuronosyl transferase induction by efavirenz; and (ii) a plasma protein displacement of valproate by efavirenz with subsequent increased elimination of the free fraction.