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Our previous studies suggest that P\u2010glycoprotein (P\u2010gp)\u2010mediated drug interactions may lead to increased gastrointestinal absorption of pimozide and its accumulation in cardiomyocytes, thereby enhancing the inhibitory effect of hERG channels. There is a paucity of epidemiological studies examining the risk of QT prolongation by antipsychotic drugs in terms of P\u2010gp\u2010mediated interactions with concomitant drugs. Therefore, using the Japanese Adverse Event Reporting Database, we investigated whether the risk of QT prolongation triggered by antipsychotic drugs associated with hERG inhibition is affected by the concomitant use of selective serotonin reuptake inhibitors (SSRIs) associated with P\u2010gp inhibition. The results showed that the frequency of QT prolongation increased when the antipsychotic drugs quetiapine and sulpiride, which are P\u2010gp substrates, were combined with SSRIs with P\u2010gp inhibition. In contrast, no association with QT prolongation was observed in patients on non\u2010P\u2010gp\u2010substrate antipsychotics, irrespective of the P\u2010gp inhibitory effect of the concomitant SSRI. These results suggest that P\u2010gp\u2010mediated interactions are a risk factor for antipsychotic\u2010induced QT prolongation. There is a need for further investigation into the risks of specific drug combinations.<\/jats:p>","DOI":"10.1002\/jcph.2343","type":"journal-article","created":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T05:29:45Z","timestamp":1693632585000},"page":"118-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["P\u2010Glycoprotein\u2010Mediated Interaction Is a Risk Factor for QT Prolongation in Concomitant Use of Antipsychotics and SSRIs as P\u2010Glycoprotein\u2010Mediated Inhibitors: Analysis of the Japanese Adverse Drug Event Report Database"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2067-5844","authenticated-orcid":false,"given":"Hiroki","family":"Morishita","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacokinetics Graduate School of Pharmaceutical Sciences Takasaki University of Health and Welfare  Takasaki Gunma Japan"},{"name":"Department of Pharmacy Saiseikai Maebashi Hospital  Maebashi Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyanage Manosika Buddhini","family":"Perera","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics Faculty of Pharmacy Takasaki University of Health and Welfare  Takasaki Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Sunakawa","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics Faculty of Pharmacy Takasaki University of Health and Welfare  Takasaki Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satsuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics Faculty of Pharmacy Takasaki University of Health and Welfare  Takasaki Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Saiseikai Maebashi Hospital  Maebashi Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuo","family":"Ogihara","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacokinetics Graduate School of Pharmaceutical Sciences Takasaki University of Health and Welfare  Takasaki Gunma Japan"},{"name":"Laboratory of Biopharmaceutics Faculty of Pharmacy Takasaki University of Health and Welfare  Takasaki Gunma Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_2_1","DOI":"10.1002\/hup.915"},{"doi-asserted-by":"publisher","key":"e_1_2_9_3_1","DOI":"10.1124\/pr.110.003723"},{"doi-asserted-by":"publisher","key":"e_1_2_9_4_1","DOI":"10.1080\/0886022X.2019.1707098"},{"doi-asserted-by":"publisher","key":"e_1_2_9_5_1","DOI":"10.3390\/jcm8111866"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1016\/j.tips.2017.06.004"},{"doi-asserted-by":"publisher","key":"e_1_2_9_7_1","DOI":"10.1016\/s0014\u20102999(02)02074\u20105"},{"doi-asserted-by":"publisher","key":"e_1_2_9_8_1","DOI":"10.2217\/pgs.11.44"},{"doi-asserted-by":"publisher","key":"e_1_2_9_9_1","DOI":"10.1371\/journal.pone.0232438"},{"doi-asserted-by":"publisher","key":"e_1_2_9_10_1","DOI":"10.1016\/j.xphs.2022.09.025"},{"doi-asserted-by":"publisher","key":"e_1_2_9_11_1","DOI":"10.1093\/ijnp\/pyz068"},{"doi-asserted-by":"publisher","key":"e_1_2_9_12_1","DOI":"10.1016\/s0014\u20102999(00)00123\u20100"},{"doi-asserted-by":"publisher","key":"e_1_2_9_13_1","DOI":"10.1016\/j.neulet.2015.10.039"},{"doi-asserted-by":"publisher","key":"e_1_2_9_14_1","DOI":"10.1016\/j.neulet.2017.11.029"},{"doi-asserted-by":"publisher","key":"e_1_2_9_15_1","DOI":"10.1177\/1091581809337261"},{"doi-asserted-by":"publisher","key":"e_1_2_9_16_1","DOI":"10.1007\/s00210\u2010017\u20101364\u20105"},{"doi-asserted-by":"publisher","key":"e_1_2_9_17_1","DOI":"10.1016\/j.ejphar.2013.01.039"},{"doi-asserted-by":"publisher","key":"e_1_2_9_18_1","DOI":"10.1038\/sj.bjp.0700989"},{"doi-asserted-by":"publisher","key":"e_1_2_9_19_1","DOI":"10.1038\/sj.bjp.0705283"},{"doi-asserted-by":"publisher","key":"e_1_2_9_20_1","DOI":"10.1038\/sj.bjp.0706744"},{"doi-asserted-by":"publisher","key":"e_1_2_9_21_1","DOI":"10.2165\/00002018\u2010200528010\u201000003"},{"doi-asserted-by":"publisher","key":"e_1_2_9_22_1","DOI":"10.1016\/j.ejphar.2006.06.009"},{"doi-asserted-by":"publisher","key":"e_1_2_9_23_1","DOI":"10.1002\/phar.2087"},{"doi-asserted-by":"publisher","key":"e_1_2_9_24_1","DOI":"10.1016\/s0024\u20103205(02)01680\u20106"},{"doi-asserted-by":"publisher","key":"e_1_2_9_25_1","DOI":"10.1248\/bpb.25.885"},{"doi-asserted-by":"publisher","key":"e_1_2_9_26_1","DOI":"10.2217\/pgs.11.55"},{"doi-asserted-by":"publisher","key":"e_1_2_9_27_1","DOI":"10.1211\/0022357043969"},{"unstructured":"MedDRA. 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