The effects of aripiprazole and olanzapine on pupillary light reflex and its relationship with pharmacogenetics in a randomized multiple-dose trial
| Autor: | Manuel Román, Samuel Martín, Francisco Abad-Santos, Miriam Saiz-Rodríguez, Gina Mejía, Dolores Ochoa, Pablo Zubiaur, Daniel Romero-Palacián, Alejandro de Miguel-Cáceres, Dora Koller, Susana Almenara, Aneta Wojnicz, Marcos Navares-Gómez |
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| Přispěvatelé: | UAM. Departamento de Farmacología, Instituto Teófilo Hernando de I+D del Medicamento (ITH), Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP) |
| Rok vydání: | 2020 |
| Předmět: |
Olanzapine
medicine.medical_treatment Aripiprazole Pharmacology 030226 pharmacology & pharmacy Pupil 03 medical and health sciences Benzodiazepines 0302 clinical medicine Reflex Medicine Antipsychotics Humans Pharmacology (medical) Pharmacokinetics 030212 general & internal medicine Pupillary light reflex Antipsychotic business.industry Original Articles Farmacia 3. Good health Genetics and pharmacogenetics Pharmacodynamics Pharmacogenetics Schizophrenia Pupillography Original Article business Pupillometry medicine.drug Antipsychotic Agents |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM Consejo Superior de Investigaciones Científicas (CSIC) Biblos-e Archivo: Repositorio Institucional de la UAM Universidad Autónoma de Madrid British Journal of Clinical Pharmacology |
| ISSN: | 1365-2125 |
| Popis: | 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. Consejería 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 |
| Databáze: | OpenAIRE |
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