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

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.

• Authors: Pablo Zubiaur, Paula Soria-Chacartegui, Dora Koller, Marcos Navares-Gómez, Dolores Ochoa, Susana Almenara, Miriam Saiz-Rodríguez, Gina Mejía-Abril, Gonzalo Villapalos-García, Manuel Román, Samuel Martín-Vílchez, Francisco Abad-Santos
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 133 Pg. 111087 (Jan 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 33378980 (Publication Type: Journal Article, Observational Study)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• ABCC2 protein, human
• Antipsychotic Agents
• Enzymes
• Membrane Transport Proteins
• Multidrug Resistance-Associated Protein 2
• Olanzapine

Topics

• Adult
• Antipsychotic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Biotransformation
• Clinical Trials as Topic
• Enzymes (genetics)
• Female
• Genetic Association Studies
• Genotype
• Healthy Volunteers
• Humans
• Male
• Membrane Transport Proteins (genetics)
• Multidrug Resistance-Associated Protein 2
• Olanzapine (administration & dosage, adverse effects, pharmacokinetics)
• Pharmacogenomic Variants
• Phenotype
• Polymorphism, Genetic
• Risk Factors
• Young Adult