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Genetic variants in cytochrome P450 (<jats:italic>CYP<\/jats:italic>), dopamine receptor (<jats:italic>DRD2<\/jats:italic>, <jats:italic>DRD3<\/jats:italic>), serotonin receptor (<jats:italic>HTR2A<\/jats:italic>, <jats:italic>HTR2C<\/jats:italic>) and ATP\u2010binding cassette subfamily B (<jats:italic>ABCB1<\/jats:italic>) genes, among others, were previously associated with the pharmacokinetics and pharmacodynamics of antipsychotic drugs. Our aim was to evaluate the effects of <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=34\">aripiprazole<\/jats:ext-link> and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.guidetopharmacology.org\/GRAC\/LigandDisplayForward?ligandId=47\">olanzapine<\/jats:ext-link> on pupillary light reflex related to pharmacogenetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty\u2010four 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\u2010aripiprazole and olanzapine plasma concentrations were measured by high\u2010performance liquid chromatography\u2013tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>P<\/jats:italic> &lt; .05). Olanzapine only altered minimum pupil size (<jats:italic>P<\/jats:italic> = .046). Polymorphisms in <jats:italic>CYP3A<\/jats:italic>, <jats:italic>HTR2A<\/jats:italic>, <jats:italic>UGT1A1<\/jats:italic>, <jats:italic>DRD2<\/jats:italic> and <jats:italic>ABCB1<\/jats:italic> affected pupil size, the time of onset of constriction, pupil recovery and constriction velocity. Aripiprazole, dehydro\u2010aripiprazole and olanzapine pharmacokinetics were significantly affected by polymorphisms in <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>CYP3A<\/jats:italic>, <jats:italic>CYP1A2<\/jats:italic>, <jats:italic>ABCB1<\/jats:italic> and <jats:italic>UGT1A1<\/jats:italic> genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, aripiprazole and its main metabolite, dehydro\u2010aripiprazole 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\u2010aripiprazole and olanzapine pharmacokinetics. Pupillography could be a useful tool for the determination of autonomic nerve activity during antipsychotic treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14300","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T15:25:11Z","timestamp":1586186711000},"page":"2051-2062","source":"Crossref","is-referenced-by-count":25,"title":["The effects of aripiprazole and olanzapine on pupillary light reflex and its relationship with pharmacogenetics in a randomized multiple\u2010dose trial"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-0466","authenticated-orcid":false,"given":"Dora","family":"Koller","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Te\u00f3filo Hernando, Pharmacology Department, Faculty of Medicine Autonomous University of Madrid  Madrid 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