Adding valproate to lamotrigine: a study of their pharmacokinetic interaction.

The addition of valproic acid (VPA) to a lamotrigine monotherapy regimen (LTG) results in a decrement of LTG clearance. Whether this effect is related to the dose or concentration at steady state (Css) of VPA is yet to be established. This study was conducted to determine whether the dose or Css of VPA were inversely related to LTG clearance in 28 patients with intractable epilepsy who were treated with a combination of LTG and VPA. Correlations between LTG clearance and the dose and Css of VPA and comparisons of LTG clearance during low and high doses of VPA demonstrated that the degree of inhibition of LTG clearance is independent of the dose and Css of VPA.