PHARMACOKINETIC INTERACTIONS AND SIDE-EFFECTS RESULTING FROM CONCOMITANT ADMINISTRATION OF LITHIUM AND DIVALPROEX SODIUM

Background: Valproic acid is added to the lithium regimens of many pat ients with bipolar disorder, especially those with mania refractory to lithium treatment. Method: We evaluated the pharmacokinetic effects a nd safety of coadministration of lithium and valproate in 16 healthy v olunteers in this randomized, placebo-controlled, two-period (12 days each) crossover trial. Valproate or placebo was given twice daily. On Days 6-10, lithium was added. Blood samples drawn on Days 5 and 10 wer e analyzed for valproate by high-pressure liquid chromatography (HPLC) and for lithium by atomic absorption spectrophotometry. Results: Lith ium pharmacokinetics were unchanged by valproate, but valproate C-max, C-min, and AUC rose slightly during lithium coadministration. Adverse events did not change significantly. Conclusion: Concomitant administ ration of lithium and valproate appears to be safe in patients with bi polar disorder.