Format

Send to

Choose Destination
See comment in PubMed Commons below
Pharmacogenomics. 2002 Mar;3(2):201-18.

Cytochrome P450 polymorphisms and response to antipsychotic therapy.

Author information

1
Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Via Consolare Valeria Gazzi, I 98125 Messina, Italy. gabriella.scordo@tiscalinet.it

Abstract

Antipsychotic drugs are used for the treatment of schizophrenia and other related psychotic disorders. The antipsychotics currently available include older or classical compounds and newer or atypical agents. Most antipsychotic drugs are highly lipophilic compounds and undergo extensive metabolism by cytochrome P450 (CYP) enzymes in order to be excreted. There is a wide interindividual variability in the biotransformation of antipsychotic drugs, resulting in pronounced differences in steady-state plasma concentrations and, possibly, in therapeutic and toxic effects, during treatment with fixed doses. Many classical and some newer antipsychotics are metabolized to a significant extent by the polymorphic CYP2D6, which shows large interindividual variation in activity. Other CYPs, especially CYP1A2 and CYP3A4, also contribute to the interindividual variability in the kinetics of antipsychotics and occurrence of drug interactions. No relationship between CYP2D6 genotype or activity and therapeutic effects of classical antipsychotic drugs has been found in the few studies performed. On the other hand, some investigations suggest that poor metabolizers (PMs) of CYP2D6 would be more prone to over-sedation and, possibly, Parkinsonism during treatment with classical antipsychotics, while other studies, mostly retrospective, have been negative or inconclusive. For the newer antipsychotics, such data are lacking. To date, CYP2D6 phenotyping and genotyping appear, therefore, to be clinically useful for dose predicting only in special cases and for a limited number of antipsychotics, while their usefulness in predicting clinical effects must be further explored.

PMID:
11972442
DOI:
10.1517/14622416.3.2.201
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Support Center