Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers
Entity
UAM. Departamento de FarmacologíaPublisher
Elsevier Masson s.r.l.Date
2020-12-08Citation
10.1016/j.biopha.2020.111087
Biomedicine & Pharmacotherapy 133 (2021): 111087
ISSN
0753-3322DOI
10.1016/j.biopha.2020.111087Funded by
D. Koller is financed by the H2020 Marie Sklodowska-Curie Innovative Training Network721236 grant. Marcos Navares-G´omez is cofinaneced by the European Social Fund and the Youth European Initiative, grant number PEJ-2018-TL/MD-11080Subjects
Cytochrome P450; Olanzapine; Pharmacogenetics; Precision medicine; MedicinaRights
© 2020 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, the Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype is not related to olanzapine response or side effects. Thus, the objective of this candidate-gene study was to investigate the effect of 72 polymorphisms in 21 genes on olanzapine pharmacokinetics and safety, including transporters (e.g. ABCB1, ABCC2, SLC22A1), receptors (e.g. DRD2, HTR2C), and enzymes (e.g. UGT, CYP and COMT), in a cohort of healthy volunteers. Polymorphisms in CYP2C9, SLC22A1, ABCB1, ABCC2, and APOC3 were related to olanzapine pharmacokinetic variability. The incidence of adverse reactions was related to several genes: palpitations to ABCB1 and SLC22A1, asthenia to ABCB1, somnolence to DRD2 and ABCB1, and dizziness to CYP2C9. However, further studies in patients are warranted to confirm the influence of these genetic polymorphisms on olanzapine pharmacokinetics and tolerability.
Files in this item
Google Scholar:Zubiaur, Pablo
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Soria-Chacartegui, Paula
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Koller, Dora
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Navares-Gómez, Marcos
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Ochoa Mazarro, María Dolores
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Almenara, Susana
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Saiz-Rodríguez, Miriam
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Mejía-Abril, Gina
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Villapalos-García, Gonzalo
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Román, Manuel
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Martín-Vílchez, Samuel
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Abad Santos, Francisco
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