Details of a Researcher - Kiyomiya, Keisuke

Comprehensive analysis of responses from ChatGPT to consumer inquiries regarding over-the-counter medications

K. Kiyomiya, T. Aomori, and H. Ohtani

Die Pharmazie （Pharmazie) 79 （ 1 ） 24 - 28 2024.02

Research paper (scientific journal), Lead author, Accepted, ISSN 0031-7144

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Background: The use of generative artificial intelligence (AI) applications such as ChatGPT is becoming increasingly popular. In Japan, consumers can purchase most over-the-counter (OTC) drugs without having to consult a pharmacist, so they may ask generative AI applications which OTC drugs they should purchase. This study aimed to systematically evaluate responses from ChatGPT to consumer inquiries about various OTC drugs. Methods: We selected 22 popular OTC drugs and 12 typical consumer characteristics, including physical and disease conditions and concomitant medications. We input a total of 264 questions (i.e., all combinations of drugs and characteristics) to ChatGPT in Japanese, asking whether it is safe for consumers with each characteristic to take these OTC drugs. We used the generic name for 10 of the 22 drugs and the brand name for the remaining 12. Responses were evaluated based on the following three criteria: 1) coherence between the question and response, 2) scientific correctness, and 3) appropriateness of the instructed actions. When we received a response that satisfied all three criteria, we input the exact same question on a different day to assess reproducibility. Results: The proportions of ChatGPT's answers that satisfied criteria 1, 2, and 3 were 79.5%, 54.5%, and 49.6%, respectively. However, the proportion of responses that satisfied all three criteria was only 20.8% (55/264); 61.8% (34/55) of these responses were reproduced when the same question was input again on a different day. Compared with questions using generic names, those using brand names resulted in lower coherence and scientific correctness. Among the 12 characteristics, the appropriateness of the instructed actions tended to be lower in responses to questions about driving and concomitant medications. Conclusions: Our study revealed that ChatGPT was less accurate in its responses and less consistent in its instructed actions compared with the package inserts. Our findings suggest that Japanese consumers should not consult ChatGPT regarding OTC medications, especially when using brand names.
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Macrolide and Ketolide Antibiotics Inhibit the Cytotoxic Effect of Trastuzumab Emtansine in HER2-Positive Breast Cancer Cells: Implication of a Potential Drug−ADC Interaction in Cancer Chemotherapy

Keisuke Kiyomiya, Ryuto Tomabechi, Naoki Saito, Kenta Watai, Tappei Takada, Yoshiyuki Shirasaka, Hisanao Kishimoto, Kei Higuchi, and Katsuhisa Inoue

molecular pharmaceutics （ACS) 20 （ 12 ） 6130 - 6139 2023.11

Research paper (scientific journal), Lead author, Accepted, ISSN 15438384

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Macrolides are widely used for the long-term treatment of infections and chronic inflammatory diseases. The pharmacokinetic features of macrolides include extensive tissue distribution because of favorable membrane permeability and accumulation within lysosomes. Trastuzumab emtansine (T-DM1), a HER2-targeting antibody-drug conjugate (ADC), is catabolized in the lysosomes, where Lys-SMCC-DM1, a potent cytotoxic agent, is processed by proteinase degradation and subsequently released from the lysosomes to the cytoplasm through the lysosomal membrane transporter SLC46A3, resulting in an antitumor effect. We recently demonstrated that erythromycin and clarithromycin inhibit SLC46A3 and attenuate the cytotoxicity of T-DM1; however, the effect of other macrolides and ketolides has not been determined. In this study, we evaluated the effect of macrolide and ketolide antibiotics on T-DM1 cytotoxicity in a human breast cancer cell line, KPL-4. Macrolides used in the clinic, such as roxithromycin, azithromycin, and josamycin, as well as solithromycin, a ketolide under clinical development, significantly attenuated T-DM1 cytotoxicity in addition to erythromycin and clarithromycin. Of these, azithromycin was the most potent inhibitor of T-DM1 efficacy. These antibiotics significantly inhibited the transport function of SLC46A3 in a concentration-dependent manner. Moreover, these compounds extensively accumulated in the lysosomes at the levels estimated to be 0.41-13.6 mM when cells were incubated with them at a 2 μM concentration. The immunofluorescence staining of trastuzumab revealed that azithromycin and solithromycin inhibit the degradation of T-DM1 in the lysosomes. These results suggest that the attenuation of T-DM1 cytotoxicity by macrolide and ketolide antibiotics involves their lysosomal accumulation and results in their greater lysosomal concentrations to inhibit the SLC46A3 function and T-DM1 degradation. This suggests a potential drug-ADC interaction during cancer chemotherapy.
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病棟薬剤業務による医師・看護師の業務負担軽減の定量的評価

佐々木駿一, 津田壮一郎, 清宮啓介, 中田英夫, 村松博, 青森達, 大谷壽一

医療薬学（(一社)日本医療薬学会) 49 （ 10 ） 357 - 364 2023.10

Research paper (scientific journal), Accepted, ISSN 1346-342X
SLC46A3 is a lysosomal proton-coupled steroid conjugate and bile acid transporter involved in transport of active catabolites of T-DM1

Ryuto Tomabechi, Hisanao Kishimoto, Taeka Sato, Naoki Saito, Keisuke Kiyomiya, Tappei Takada, Kei Higuchi, Yoshiyuki Shirasaka, Katsuhisa Inoue

PNAS Nexus （PNAS Nexus) 1 （ 3 ） 1 - 11 2022.05

Research paper (scientific journal), Joint Work, Accepted

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Antibody drug conjugates (ADCs) represent a new class of cancer therapeutics that enable targeted delivery of cytotoxic drugs to cancer cells. Although clinical efficacy has been demonstrated for ADC therapies, resistance to these conjugates may occur. Recently, SLC46A3, a lysosomal membrane protein, was revealed to regulate the efficacy of trastuzumab emtansine (T-DM1), a noncleavable ADC that has been widely used for treating breast cancer. However, the role of SLC46A3 in mediating T-DM1 cytotoxicity remains unclear. In this study, we discovered the function of SLC46A3 as a novel proton-coupled steroid conjugate and bile acid transporter. SLC46A3 preferentially recognized lipophilic steroid conjugates and bile acids as endogenous substrates. In addition, we found that SLC46A3 directly transports Lys-SMCC-DM1, a major catabolite of T-DM1, and potent SLC46A3 inhibitors attenuate the cytotoxic effects of T-DM1, suggesting a role in the escape of Lys-SMCC-DM1 from the lysosome into the cytoplasm. Our findings reveal the molecular mechanism by which T-DM1 kills cancer cells and may contribute to the rational development of ADCs that target SLC46A3.
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診療科間における情報共有を可能とした妊娠・授乳と薬相談業務の取組み

鈴木靖奈, 三浦あす美, 滝澤詠美子, 杉谷綾佳, 西木美優, 川島沙織, 櫻井しおり, 潮田佳奈, 玉川知鮎, 清宮啓介, 小谷宙, 山吉康子, 村松博, 青森達

日本病院薬剤師会雑誌（(一社)日本病院薬剤師会) 58 （ 4 ） 408 - 415 2022.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 1341-8815

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慶應義塾大学病院では、出産・授乳に関する薬剤の情報発信を薬剤部で一元化する「妊娠・授乳と薬相談業務」を2018年に開始した。妊婦・授乳婦への薬物療法に関する回答書を作成し、医師・患者へ情報提供している。本研究では2018年1月～2020年12月の相談件数、内容、薬剤の調査回数、相談後の転帰の把握を目的とした。相談件数は2018年31件、2019年56件、2020年70件で、内訳は「妊娠と薬」で54件、「授乳と薬」で99件、「妊孕性と薬」で4件であった。最も調査が多かった薬剤はゾルピデムの16回であり、薬効別では抗不安薬・睡眠薬が最も多く全体の約25%を占めていた。相談件数は年々増加し、本業務の需要性は高いと考えられた。問診票と回答書は患者の電子カルテ上に保存されるため、複数の診療科を併診している患者でも、診療科間における情報共有が可能となり、治療に貢献することができると考える。(著者抄録)

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Papers, etc., Registered in KOARA 【 Display / hide 】

The effect of 8-disease-coordination-sheet on the rubric evaluation in the practical training of Pharmacy students

Kiyomiya, Keisuke

学事振興資金研究成果実績報告書（慶應義塾大学) 2018

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Presentations 【 Display / hide 】

ChatGPTにOTC薬の服薬を相談するとどうなるか

清宮啓介, 青森達, 大谷壽一

第６回フレッシャーズ・カンファランス,

2023.06
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Oral presentation (general)
SLC46A3遺伝子多型が輸送機能とトラスツズマブエムタンシンの殺細胞効果へ与える影響

齊藤直希, 苫米地隆人, 川喜多佑香, 清宮啓介, 岸本久直, 樋口慧, 井上勝央

日本薬剤学会年会講演要旨集,

2023.05
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(公社)日本薬剤学会
MeDaCaアプリを活用した妊娠・授乳と薬相談　オンライン相談の取り組み

櫻井しおり, 三浦あす美, 鈴木靖奈, 小谷宙, 清宮啓介, 村松博, 青森達, 大谷壽一

日本薬学会年会要旨集,

2022.03
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(公社)日本薬学会
コロナ禍におけるがん患者の親をもつ子どもへの支援　アバターロボットを活用したオンラインでの取り組み

近藤咲子, 阿部晃子, 石井有紀, 内田智栄, 大野真里, 片岡美樹, 北村悦子, 清宮啓介, 久住真有美, 新藤悦子, 仙波美幸, 竹内麻理, 田中康代, 茶園美香, 中里雅子, 伏見寿子, 伏見幸弘, 南島一也, 陣崎雅弘, 熊谷祐美

Palliative Care Research,

2021.06
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(NPO)日本緩和医療学会
「妊娠・授乳と薬相談業務」による情報提供後の転帰調査

清宮啓介, 小谷宙, 三浦あす美, 鈴木靖奈, 村松博, 青森達

第30回医療薬学会年会,

2020.10
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Poster presentation