Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers - 19/12/20
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Graphical abstract |
Highlights |
• | CYP2C9 phenotype and SLC22A1 and APOC3 polymorphism were related to variability in olanzapine pharmacokinetics. |
• | CYP1A2 and CYP2D6 polymorphism, previously reported to alter olanzapine pharmacokinetics, had no effect in this work. |
• | CYP2C9 phenotype and SLC22A1 polymorphism were related to a higher risk for dizziness or palpitations and ABCB1 and DRD2 polymorphism to somnolence. |
• | Polymorphism of other metabolizing enzymes genes or transporter genes may be related to olanzapine pharmacokinetic variability. |
• | For the relationship with olanzapine pharmacokinetic variability, metabolizing enzyme and transporter gene polymorphism should be further studied. |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Olanzapine, Pharmacogenetics, Precision medicine, Cytochrome P450
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Vol 133
Article 111087- janvier 2021 Retour au numéro
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