The role of cytochrome P450 enzymes in the metabolism of risperidone and its clinical relevance for drug interactions

R. Berecz, P. Dorado, A. De La Rubia, M. C. Cáceres, I. Degrell, A. Llerena

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

In the recent years it has been increasingly recognized that pharmacogenetical factors play an important role in the drug treatment. These factors may influence the appearance of side-effects and drug interactions due to interindividual differences in the activity of metabolizing enzymes. Risperidone in humans is mainly metabolized to 9-hydroxyrisperidone by the polymorphic cytochrome enzyme P450 2D6 (CYP2D6). Plasma concentrations of risperidone and 9-hydroxyrisperidone show large interindividual variability, which may be partly related to the activity of the CYP2D6 enzyme. Around seven percent of Caucasians have a genetically inherited impaired activity of the CYP2D6 enzyme. Debrisoquine metabolic ratio (a marker of CYP2D6 activity) and the number of CYP2D6 active genes have been related to risperidone plasma concentrations among patients during steady-state conditions. A large number drugs have been described to be metabolized by CYP2D6, and it is therefore important to evaluate the clinical significance of the impaired metabolism and possible drug interactions on the enzyme. Since risperidone/9-hydroxyrisperidone ratio strongly correlates with CYP2D6 enzyme activity and the number of CYP2D6 active genes, thus it might be an useful tool in clinical practice to estimate the possible risk of drug interactions due to impaired CYP2D6 enzyme activity. CYP3A4 is the most abundant drug metabolizing enzyme in humans, and in vitro and in vivo results suggest also a role for the enzyme in risperidone metabolism. The consideration of the implication of cytochrome P450 enzymes in risperidone metabolism may help to individualize dose schemes in order to avoid interactions and potentially dangerous side-effects, such us QTc interval lengthening among patients with cardiac risk factors.

Original languageEnglish
Pages (from-to)573-579
Number of pages7
JournalCurrent Drug Targets
Volume5
Issue number6
DOIs
Publication statusPublished - Aug 2004

Fingerprint

Drug interactions
Risperidone
Cytochromes
Drug Interactions
Metabolism
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP2D6
Enzymes
Enzyme activity
Genes
Debrisoquin
Plasmas
Drug therapy
Cytochrome P-450 CYP3A
Pharmaceutical Preparations
Drug-Related Side Effects and Adverse Reactions

Keywords

  • CYP2D6
  • CYP3A4
  • Metabolism
  • Pharmacogenetics
  • Risperidone

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

The role of cytochrome P450 enzymes in the metabolism of risperidone and its clinical relevance for drug interactions. / Berecz, R.; Dorado, P.; De La Rubia, A.; Cáceres, M. C.; Degrell, I.; Llerena, A.

In: Current Drug Targets, Vol. 5, No. 6, 08.2004, p. 573-579.

Research output: Contribution to journalArticle

Berecz, R. ; Dorado, P. ; De La Rubia, A. ; Cáceres, M. C. ; Degrell, I. ; Llerena, A. / The role of cytochrome P450 enzymes in the metabolism of risperidone and its clinical relevance for drug interactions. In: Current Drug Targets. 2004 ; Vol. 5, No. 6. pp. 573-579.
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