The effects of aripiprazole and olanzapine on pupillary light reflex and its relationship with pharmacogenetics in a randomized multiple-dose trial
EntityUAM. Departamento de Farmacología; Instituto Teófilo Hernando de I+D del Medicamento (ITH); Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP)
PublisherJohn Wiley & Sons Ltd on behalf of British Pharmacological Society
10.1111/bcp.14300British Journal of Clinical Pharmacology 86.10 (2020): 2051-2062
Funded byConsejería de Educación, Juventud y Deporte, Comunidad de Madrid, Grant/Award Number: PEJD-2017-PRE/BMD-4164; H2020 Marie Skłodowska-Curie Actions, Grant/Award Number: 721236
SubjectsAntipsychotics; Genetics and pharmacogenetics; Pharmacodynamics; Pharmacokinetics; Schizophrenia; Farmacia
Rights© 2020 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.
Aims: Pupillography is a noninvasive and cost-effective method to determine autonomic nerve activity. Genetic variants in cytochrome P450 (CYP), dopamine receptor (DRD2, DRD3), serotonin receptor (HTR2A, HTR2C) and ATP-binding cassette subfamily B (ABCB1) genes, among others, were previously associated with the pharmacokinetics and pharmacodynamics of antipsychotic drugs. Our aim was to evaluate the effects of aripiprazole and olanzapine on pupillary light reflex related to pharmacogenetics. Methods: Twenty-four healthy volunteers receiving 5 oral doses of 10 mg aripiprazole and 5 mg olanzapine tablets were genotyped for 46 polymorphisms by quantitative polymerase chain reaction. Pupil examination was performed by automated pupillometry. Aripiprazole, dehydro-aripiprazole and olanzapine plasma concentrations were measured by high-performance liquid chromatography–tandem mass spectrometry. Results: Aripiprazole affected pupil contraction: it caused dilatation after the administration of the first dose, then caused constriction after each dosing. It induced changes in all pupillometric parameters (P '.05). Olanzapine only altered minimum pupil size (P =.046). Polymorphisms in CYP3A, HTR2A, UGT1A1, DRD2 and ABCB1 affected pupil size, the time of onset of constriction, pupil recovery and constriction velocity. Aripiprazole, dehydro-aripiprazole and olanzapine pharmacokinetics were significantly affected by polymorphisms in CYP2D6, CYP3A, CYP1A2, ABCB1 and UGT1A1 genes. Conclusions: In conclusion, aripiprazole and its main metabolite, dehydro-aripiprazole altered pupil contraction, but olanzapine did not have such an effect. Many polymorphisms may influence pupillometric parameters and several polymorphisms had an effect on aripiprazole, dehydro-aripiprazole and olanzapine pharmacokinetics. Pupillography could be a useful tool for the determination of autonomic nerve activity during antipsychotic treatment.
Google Scholar:Koller, Dora - Saiz-Rodríguez, Miriam - Zubiaur, Pablo - Ochoa Mazarro, María Dolores - Almenara, Susana - Román, Manuel - Romero-Palacián, Daniel - de Miguel-Cáceres, Alejandro - Martín, Samuel - Navares-Gómez, Marcos - Mejía, Gina - Wojnicz, Aneta - Abad Santos, Francisco
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