Valproic acid disposition and protein binding in pregnancy.

Nine epileptic women were followed prospectively through pregnancy on a monthly basis. At each visit, total and free serum valproic acid levels and albumin levels were obtained. Assays were done by gas-liquid chromatography, and free drug was separated by ultrafiltration. Despite an upward dose adjustment in four patients, total valproic acid levels declined as pregnancy proceeded, but free levels did not. Plasma free fractions and clearances increased, but intrinsic clearances, which were adjusted for changes in body weight, remained unchanged.