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Clinical Trial
. 1996 May;57(5):204-6.

Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium

G R Granneman  1 , D W Schneck, J H Cavanaugh, G F Witt
Affiliations
  • PMID: 8626351
Clinical Trial

Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium

G R Granneman et al. J Clin Psychiatry. 1996 May.

Abstract

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.

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