AI Article Synopsis
- Quetiapine is an atypical antipsychotic used primarily for schizophrenia and bipolar disorder, and the study aimed to explore how genetic variations impact its metabolism and potential side effects.
- 49 healthy participants were included in two clinical trials, where researchers analyzed 80 genetic variants from 19 pharmacogenes, particularly those related to the cytochrome P450 enzyme system.
- Key findings showed that specific genetic variants (like the rs13306278 T allele) were linked to increased quetiapine exposure and that certain enzymes (CYP3A5 and possibly CYP2B6) significantly influence its metabolism, suggesting the need for more research to validate these results.
Article Abstract
Quetiapine is an atypical antipsychotic widely used for the treatment of schizophrenia and the depressive episodes of bipolar disorder. The aim of this work was to investigate the effect of variants in relevant pharmacogenes in the pharmacokinetics of quetiapine and to exploratorily evaluate adverse drug reaction (ADR) incidence based on genetic polymorphism. Specifically, 49 healthy volunteers enrolled in two bioequivalence clinical trials were included in this study. In addition, 80 variants in 19 relevant pharmacogenes were genotyped, including cytochrome P450 (CYP) genes, catechol-O-methyl transferase (), other enzymes (e.g., or ), and transporters (e.g., , or ). The rs13306278 T allele was significantly related to quetiapine-increased exposure. We demonstrated the existence of quetiapine derivatives with a catechol-like structure (7,8-dihydroxi-quetiapine and 7,8-dihydroxi-N-desalkyl-quetiapine), which would be COMT metabolites and would explain quetiapine accumulation through CYP2D6 and CYP3A4 negative feedback. Moreover, CYP3A5 and phenotypes were related to quetiapine exposure variability, which confirms (for CYP3A5) and suggests (for CYP2B6) that these enzymes play an important role in quetiapine's metabolism. Finally, the rs2231142 T allele was related to quetiapine accumulation. Further studies are required to confirm the clinical relevance of our findings.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540141 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics13101573 | DOI Listing |
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