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 (C-ss) of VPA is yet to be established. This study was conducted to determine whether the dose or C-ss 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 C-ss 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 C-ss of VPA.