Impact of polymorphisms in transporter and metabolizing enzyme genes on olanzapine pharmacokinetics and safety in healthy volunteers

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, Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype not related to olanzapine response or side effects. Thus, objective this candidate-gene study was investigate effect 72 polymorphisms in 21 genes pharmacokinetics and safety, including transporters (e.g. ABCB1, ABCC2, SLC22A1), receptors DRD2, HTR2C), enzymes UGT, CYP COMT), a cohort healthy volunteers. Polymorphisms CYP2C9, SLC22A1, APOC3 were pharmacokinetic variability. The incidence reactions several genes: palpitations ABCB1 asthenia somnolence DRD2 dizziness CYP2C9. However, further studies patients warranted confirm influence these genetic tolerability.