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 patients with bipolar disorder, especially those with mania refractory to lithium treatment.


METHODS
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.


CONCLUSIONS
Concomitant administration of lithium and valproate appears to be safe in patients with bipolar disorder.
Granneman
G R
GR
Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Schneck
D W
DW
Cavanaugh
J H
JH
Witt
G F
GF
D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008094:Lithium / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010919:Placebos; D013054:Spectrophotometry, Atomic; D014635:Valproic Acid / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*
D010919:Placebos; D014635:Valproic Acid; D008094:Lithium