| アブストラクト | The inhibition of human ether-a-go-go-related gene (hERG) channels is a known cause of QT prolongation triggered by antipsychotic drugs. Our previous studies suggest that P-glycoprotein (P-gp)-mediated 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-gp-mediated 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-gp inhibition. The results showed that the frequency of QT prolongation increased when the antipsychotic drugs quetiapine and sulpiride, which are P-gp substrates, were combined with SSRIs with P-gp inhibition. In contrast, no association with QT prolongation was observed in patients on non-P-gp-substrate antipsychotics, irrespective of the P-gp inhibitory effect of the concomitant SSRI. These results suggest that P-gp-mediated interactions are a risk factor for antipsychotic-induced QT prolongation. There is a need for further investigation into the risks of specific drug combinations. |
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| ジャーナル名 | Journal of clinical pharmacology |
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| 投稿日 | 2023/9/2 |
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| 投稿者 | Morishita, Hiroki; Perera, Liyanage Manosika Buddhini; Sunakawa, Hiroki; Kimura, Satsuki; Yoshida, Hitoshi; Ogihara, Takuo |
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| 組織名 | Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical;Sciences, Takasaki University of Health and Welfare, Takasaki, Gunma, Japan.;Department of Pharmacy, Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan.;Laboratory of Biopharmaceutics, Faculty of Pharmacy, Takasaki University of;Health and Welfare, Takasaki, Gunma, Japan. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37658631/ |
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