Abstract
Second-generation antipsychotic metabolism is mainly carried out by the CYP450 superfamily, which is highly polymorphic. Therefore, knowing the influence of the different known CYP450 polymorphisms on antipsychotic plasmatic levels and, consequently, the biological effect could contribute to a deeper knowledge of interindividual antipsychotic treatment variability, prompting possible solutions. Considering this, this state of the art review aimed to summarize the current knowledge about the influence of the diverse characterized phenotypes on the metabolism of the most used second-generation antipsychotics. Forty studies describing different single nucleotide polymorphisms (SNPs) associated with the genes CYP1A2, CYP2D6, CYP3A4, CYP3A5, and ABCB1 and their influence on pharmacokinetics of olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Most of the authors concluded that although significant differences in the pharmacokinetic parameters between the different phenotypes could be observed, more thorough studies describing pharmacokinetic interactions and environmental conditions, among other variables, are needed to fully comprehend these pharmacogenetic interactions.
Highlights
In order to achieve these objectives, the search was focused on the studies published between January 2009 and July 2021, in which the pharmacokinetic parameters related to the antipsychotic treatment of individuals over 16 years were evaluated by pharmacogenetic testing, within the framework of an empirical investigation, alongside evaluating the psychopathological status of the patients and/or the adverse effects associated with the use of psychoactive drugs and/or the plasma levels of the metabolites derived from the drug or the metabolites associated with a side effect of the drug
The effects of the studied genes variability on risperidone metabolism were described in 17 studies; four studies were focused on olanzapine; 12—on aripiprazole; six—on quetiapine, and eight—on clozapine (Supplementary Materials, Table S1)
From our point of view, CYP1A2 genetics and pharmacokinetics related to antipsychotic drugs needs to be more thoroughly studied to reach more definite conclusions but CYP1A2 polymorphisms could be clinically relevant when considering patients exposed to inductors, and the prescriber should be aware when planning the pharmacotherapy of such patients
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Schizophrenic disorders are a group of severe mental diseases that have an estimated annual incidence of 15.2 per 100,000 patients, though the exact prevalence can oscillate between 3.3‰ and 7.2‰ [1]. Schizophrenia is mainly considered a chronic disorder that may follow several patterns that partly define the illness prognosis. One of the conditioning factors of the prognosis is the response to antipsychotic agents
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