Effect of valproate on olanzapine plasma concentrations in patients with bipolar or schizoaffective disorder

Edoardo Spina, Concetta D'Arrigo, Vincenza Santoro, Maria Rosaria Muscatello, Gianluca Pandolfo, Rocco Zoccali, Francisco J. Diaz, Jose De Leon

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The effect of valproate on the steady-state plasma concentrations of olanzapine was investigated in 18 patients with bipolar or schizoaffective disorder. Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate coadministration, mean plasma olanzapine concentrations decreased significantly from 32.9 ± 9.7 ng/mL at baseline to 27.4 ± 9.8 ng/mL at week 2 (P = 0.02), and to 26.9 ± 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma olanzapine concentrations. Valproate coadministration with olanzapine was well tolerated and no patient showed a worsening of his or her psychopathological condition. These findings indicate that valproate, at doses of up to 2000 mg/d, is associated with a minimal, presumably not clinically significant, decrease in plasma olanzapine concentrations, possibly as a result of induction of olanzapine metabolism. New studies are needed to confirm that valproate could have mild inductive effects.

Original languageEnglish
Pages (from-to)758-763
Number of pages6
JournalTherapeutic Drug Monitoring
Volume31
Issue number6
DOIs
StatePublished - Dec 2009

Keywords

  • Drug interaction
  • Olanzapine
  • Pharmacokinetics
  • Therapeutic drug monitoring
  • Valproate

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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