Lithium and valproate combined administration: acute behavioural effects and drug plasma levels

Drug plasma concentrations and behavioural effects of acute combined administration of lithium and valproic acid were studied in normonatraemic and hyponatraemic rats. Hyponatraemia was induced two hours before drug administration and behavioural observations lasted for two additional hours. Blood was collected by the end of the behavioural observation. The higher doses of valproic acid (360 mg/kg) or lithium (2 mEq/kg) induced more head-shakes and higher plasma concentration than 180 mg/kg of valproic acid or lithium 1 mEq/kg, respectively. Valproic acid and lithium administered separately induced more head shakes and higher drug plasma levels in hyponatraemic rats than in normonatraemic animals. Combined administration of valproic acid (180 mg/kg) and lithium (2 mEq/kg) produced a supra-aditive effect in head-shakes. The drug interaction between lithium and valproic acid induced a decrease in valproic acid plasma level and an increase in lithium plasma levels.