Plasma concentrations of risperidone and 9-hydroxyrisperidone: Effect of comedication with carbamazepine or valproate

Edoardo Spina, Angela Avenoso, Gabriella Facciolà, Monica Salemi, Maria G. Scordo, Tiberio Giacobello, Aldo G. Madia, Emilio Perucca

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

To evaluate the pharmacokinetic interaction between risperidone and the mood-stabilizing agents carbamazepine and valproic acid, steady state plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-risperidone) were compared in patients treated with risperidone alone (controls, n = 23) and in patients comedicated with carbamazepine (n = 11) or sodium valproate (n = 10). The three groups were matched for sex, age, body weight, and antipsychotic dosage. Plasma concentrations of risperidone and 9-OH-risperidone did not differ between valproate-comedicated patients and controls. By contrast, the concentrations of both compounds were lower in patients taking carbamazepine, although the difference reached statistical significance only for the metabolite (p <0.001). The sum of the concentrations of risperidone and 9-OH-risperidone in patients receiving carbamazepine (median 44 nmol/L) was also significantly lower than in patients receiving valproate (168 nmol/L) and in controls (150 nmol/L). In five patients assessed with and without carbamazepine comedication, dose-normalized plasma risperidone and 9-OH-risperidone concentrations were significantly lower when the patients received combination therapy than when they received risperidone alone. In three patients assessed with and without valproate, no major changes in the levels of risperidone and its metabolite were observed. These findings demonstrate that carbamazepine markedly decreases the plasma concentrations of risperidone and its active 9-OH-metabolite, probably by inducing CYP3A4-mediated metabolism. This interaction is likely to be clinically significant. Conversely, valproic acid does not cause any major change in plasma antipsychotic levels.

Original languageEnglish
Pages (from-to)481-485
Number of pages5
JournalTherapeutic Drug Monitoring
Volume22
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Risperidone
Carbamazepine
Valproic Acid
Plasmas
Metabolites
Antipsychotic Agents
Paliperidone Palmitate
Cytochrome P-450 CYP3A
Pharmacokinetics
Excipients
Metabolism
hydroxide ion
Research Design
Body Weight

Keywords

  • 9-Hydroxyrisperidone
  • Carbamazepine
  • CYP3A4
  • Drug interaction
  • Risperidone
  • Valproic acid

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health
  • Pharmacology
  • Toxicology

Cite this

Plasma concentrations of risperidone and 9-hydroxyrisperidone : Effect of comedication with carbamazepine or valproate. / Spina, Edoardo; Avenoso, Angela; Facciolà, Gabriella; Salemi, Monica; Scordo, Maria G.; Giacobello, Tiberio; Madia, Aldo G.; Perucca, Emilio.

In: Therapeutic Drug Monitoring, Vol. 22, No. 4, 2000, p. 481-485.

Research output: Contribution to journalArticle

Spina, Edoardo ; Avenoso, Angela ; Facciolà, Gabriella ; Salemi, Monica ; Scordo, Maria G. ; Giacobello, Tiberio ; Madia, Aldo G. ; Perucca, Emilio. / Plasma concentrations of risperidone and 9-hydroxyrisperidone : Effect of comedication with carbamazepine or valproate. In: Therapeutic Drug Monitoring. 2000 ; Vol. 22, No. 4. pp. 481-485.
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