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Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex
G R Granneman1, D W Schneck, J H Cavanaugh
1Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Background:
Valproic acid is added to the lithium regimens of many patients with bipolar disorder, especially those with mania refractory to lithium treatment.
Method:
We evaluated the pharmacokinetic effects and safety of coadministration of lithium and valproate in 16 healthy volunteers 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 were analyzed for valproate by high-pressure liquid chromatography (HPLC) and for lithium by atomic absorption spectrophotometry.
Results:
Lithium 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 administration of lithium and valproate appears to be safe in patients with bipolar disorder.