Details of a Researcher - Tomi, Masatoshi

Reviews, Commentaries, etc. - Tomi, Masatoshi

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【胎盤の母児支援機構とその評価】ファーマコメトリクスを応用したヒト胎児薬物曝露量予測

黒沢健, 登美斉俊, 千葉康司

細胞 ((株)ニュー・サイエンス社) 56 ( 3 ) 158 - 162 2024.03

ISSN 1346-7557

妊婦薬物治療は,母体及び胎児に対するリスクとベネフィットを考慮して行う。そのため胎児曝露量は重要であり,出産時の母体血及び臍帯血の薬物濃度比(in vivo F/M比)は,有用な指標となる。母体・胎児薬物移行性評価法としてヒト胎盤に薬物灌流を行うex vivoヒト胎盤灌流試験がある。ヒト胎盤に薬物の灌流を実験的に行い,母体-胎児間の薬物移行を検討する。大半の薬剤でex vivo試験で得られた母体-胎児濃度比(ex vivo F/M比)と,in vivo F/M比が一致することが報告されているが,digoxinなど一部の薬物では一致しない。筆者らは,既報のex vivoヒト胎盤灌流試験にファーマコメトリクス,すなわちモデリング・シミュレーション手法を応用し,この原因を明らかにすると共に,胎児曝露量を予測可能とした。本稿ではこの新たなヒト胎児曝露量予測法についてdigoxinを例に紹介する。(著者抄録)

【妊娠・授乳中の薬剤の安全性について科学する】薬物の胎児移行性評価と薬物療法

登美斉俊

Precision Medicine ((株)北隆館) 4 ( 10 ) 918 - 921 2021.09

ISSN 2434-3625

薬物の胎児移行性を評価し、その機構を理解するには、定常状態における胎児血/母体血濃度比を基準とすることが重要である。定常状態における濃度比に影響するのは薬物の脂溶性やタンパク結合率に限らず、むしろトランスポーターを介した透過クリアランスによる影響が大きい。本稿では、妊婦に用いられる薬物として血糖降下薬や甲状腺機能亢進症治療薬、ジゴキシンに焦点を当て、定常状態における濃度比に基づく胎児移行性評価と、胎児移行に果たす胎盤トランスポーターの役割、胎児への影響について概説する。(著者抄録)

Faculty challenges during the SARS-CoV-2 pandemic and the results of student questionnaires for the implementation of online and face-to-face classes

Ishikawa Satoko, Inoue Kae, Tomi Masatoshi

Japanese Journal of Pharmaceutical Education (Japan Society for Pharmaceutical Education) 5 ( 0 ) n/a 2021

ISSN 2432-4124

Review of the challenges posed by the SARS-CoV-2 pandemic at Keio University Faculty of Pharmacy. We shared the latest information needed to conduct online classes with faculty and staff, held seminars on using learning management systems, creating video content, and for copyright adherence of educational materials. For freshmen of the Faculty of Pharmacy, an online communication session was held in April of 2020 and a subsequent environment for conducting face-to-face classes once a week was implemented from June of 2020. At our campus, students were able to participate more actively as college students, have interactions with their peers, ask questions, and consult with the faculty. From questionnaires about online classes, problems facing the students were identified and presented to our faculty for purposes of improving learning content. The number of students who chose the option "I don't have an opportunity to talk with my friends" tends to decrease as the academic year of education rises. Hence, more consideration should be given particularly to the first-year students. All students tended to have relatively good impressions about online classes due to the efficiency and ability for repeated viewing of lecture content. We would like to utilize the knowledge acquired from the past 10 months to provide more effective classes and further enhance the educational impact at the Faculty of Pharmacy.

【周産期の薬】産科編　総論　薬物の経胎盤透過

登美斉俊

周産期医学 ((株)東京医学社) 50 ( 増刊 ) 46 - 48 2020.12

ISSN 0386-9881

【「今さら聞けない」をスッキリ解消する　妊娠・授乳と薬】[妊娠と薬]薬物の胎児移行性を規定するメカニズム

登美斉俊, 野村岳広

薬事 ((株)じほう) 62 ( 4 ) 729 - 734 2020.03

ISSN 0016-5980

＜Points＞▼薬物が胎盤関門を介して胎児に移行する速度は、受動拡散による透過の場合、脂溶性に依存するが、定常状態における胎児血中濃度が移行速度に比例して高くなるわけではない。▼血漿タンパク結合した薬物は胎盤関門を透過できないが、血漿タンパク結合率は100%ではない。遊離形薬物は胎盤関門を透過できるため、血漿タンパク結合率が高い薬物であっても、定常状態においては胎児血中の遊離形薬物濃度が母体血並みに高くなっている可能性は十分にある。▼胎盤関門において、母体側細胞膜の頂端膜と胎児側細胞膜の基底細胞膜には、それぞれトランスポーターが極性をもって局在し、基質薬物の胎児血への移行速度と、定常状態における胎児血中濃度の両方を規定する。(著者抄録)

【「今さら聞けない」をスッキリ解消する　妊娠・授乳と薬】[妊娠と薬]胎盤透過と薬物選択

登美斉俊, 植田有美

薬事 ((株)じほう) 62 ( 4 ) 735 - 739 2020.03

ISSN 0016-5980

＜Points＞▼母体の治療には胎盤透過性の低い薬物がより望ましく、インスリンやヘパリンなどの高分子医薬品や、プレドニゾロンのように胎盤での代謝を強く受ける薬物が代表例である。▼胎児の経胎盤治療にはチアマゾールやベタメタゾン、ジゴキシンなど、一定の胎盤透過性を有した薬物が用いられている。▼胎盤透過する薬物の胎児への影響や胎盤透過性は妊娠進行に伴い変動することがあり、チアマゾールのように妊娠初期は禁忌でも、妊娠中後期には用いられる場合がある。(著者抄録)

Committee for Academic Affairs JSSHP Research Award 2019 Basic Research Screening of an Angiotensin II Receptor Blocker with Low Adverse Fetal Effect using Adverse Event Reporting System and Mechanism of the Low Placental Transfer

Nishimura Tomohiro, Ishikawa Yu, Noguchi Saki, Tomi Masatoshi

Hypertension Research in Pregnancy (Japan Society for the Study of Hypertension in Pregnancy) 8 ( 1 ) 3 - 3 2020

ISSN 2187-5987

Objective: Administration of angiotensin II receptor blocker (ARB) to pregnant women is contraindicated due to the risk of inducing oligohydramnios. However, it is unclear if the ARBs on the market uniformly induce oligohydramnios. The aim of this study was to find an ARB that is less likely to develop oligohydramnios based on the frequency of side effects registered in the US Food and Drug Administration Adverse Event Reporting System (FAERS) and to show the mechanism of the lower risk of developing oligohydramnios in non-clinical studies.Methods: We searched for cases registered in FAERS from 2004 to 2017, investigated the frequency of adverse event records of patients taking ARB showing oligohydramnios, and compared them among ARB drugs. We compared the antihypertensive effect of the selected ARBs and their fetal transfer in the model rats of hypertensive disorder of pregnancy with administration of L-NAME, a nonselective nitric oxide synthase inhibitor. The transport activity of organic anion transporting polypeptide (OATP) 2B1 was evaluated by using HEK293 cells transiently transfected with cDNA of human OATP2B1. The drug concentrations were measured by liquid chromatography with tandem mass spectrometry.Results: Of the 6 ARBs investigated, olmesartan had the highest frequency of oligohydramnios, and irbesartan had the lowest frequency, with a 25-fold difference in reporting frequency. In pregnant hypertensive rats, both olmesartan and irbesartan showed remarkable antihypertensive effect, while only irbesartan showed the effect of improving fetal growth failure. Ratio of the plasma concentration in the fetus to that in the dam (F/M ratio) was measured. The F/M ratios of olmesartan and irbesartan were about 1.6 and 0.28, respectively, indicating that fetal transfer of irbesartan is relatively limited due to the flux in the placenta. OATP2B1 is one of drug transporters which is known to be expressed in the fetal-facing membrane in syncytiotrophoblasts. When the transport activity of both drugs by OATP2B1 was examined, it was shown that only irbesartan was transported.Conclusion: The records in the database implied that irbesartan has a low risk of increasing amniotic fluid volume among the ARB drugs. Irbesartan showed lower fetal transfer at least in rats than olmesartan and irbesartan is a substrate of OATP2B1, indicating that irbesartan may be excreted by placental OATP2B1 from fetal plasma to maternal plasma.

Report on the APSTJ Public Lecture Series 2019

Tomi Masatoshi

Journal of Pharmaceutical Science and Technology, Japan (The Academy of Pharmaceutical Science and Technology, Japan) 80 ( 2 ) 109 - 110 2020

ISSN 0372-7629

IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery

Albrecht C., Chamley L., Charnock-Jones D.S., Collins S., Fujiwara H., Golos T., Grayo S., Hannan N., Harris L., Ichizuka K., Illsley N.P., Iwashita M., Kallol S., Al-Khan A., Lash G., Nagamatsu T., Nakashima A., Niimi K., Nomoto M., Redman C., Saito S., Tanimura K., Tomi M., Usui H., Vatish M., Wolfe B., Yamamoto E., O'Tierney-Ginn P.

Placenta (Placenta) 84 9 - 13 2019.09

Article, review, commentary, editorial, etc. (international conference proceedings), ISSN 01434004

Access to Document (DOI)

妊婦への有効かつ安全な薬物治療拡大を目指した胎盤機能研究

登美斉俊

製剤機械技術学会誌 27 ( 1 ) 69 - 73 2018

Article, review, commentary, editorial, etc. (scientific journal), Single Work

【基本が身につく・考え方がわかる　エキスパートが教える薬物動態】(第2章)ADMEで考える薬物動態Q&A　分布　胎児移行性の低い薬物について教えてください

登美斉俊

薬事 ((株)じほう) 59 ( 14 ) 2810 - 2814 2017.10

ISSN 0016-5980

【いまさら聞けない薬物動態Q&A】分布　Q.胎児移行性の低い薬物について教えてください

登美斉俊

薬事 ((株)じほう) 58 ( 4 ) 666 - 669 2016.03

ISSN 0016-5980

紹介慶應義塾大学薬学部国際交流セミナーWilliam N. Charman先生講演会

登美斉俊

薬剤学 75 ( 6 ) 381 - 382 2015.11

Meeting report, Single Work

紹介第29回日本薬物動態学会・第19回国際薬物動態学会北米年会合同年会

登美斉俊

薬剤学 75 ( 2 ) 133 - 134 2015.03

Meeting report, Single Work

トランスポーターによる胎盤関門透過制御機構の解明

登美斉俊

Drug Delivery System (日本DDS学会) 28 ( 4 ) 364 - 365 2013.09

Article, review, commentary, editorial, etc. (scientific journal), Single Work

How the brain acts: Factor analysis of placebo effects

ISAWA Minae, SHINNO Akemi, NISHIMURA Tomohiro, TOMI Masatoshi, NAKASHIMA Emi

JOURNAL OF JAPANESE COSMETIC SCIENCE SOCIETY (Japanese Cosmetic Science Society) 37 ( 3 ) 197 - 200 2013.09

Research paper, summary (national, other academic conference), Joint Work, ISSN 1880-2532

Recent clinical research utilizing noninvasive functional measurement techniques has indicated that placebo effects might be therapeutically useful, because clear responses to placebo administration have been observed in patients' brains. Both physiological and mental states are affected by placebo and a role of brain receptor(s) was suggested. Factors influencing the placebo effect are the Pavlov reaction, expectation, cognition, and conditioning. Further, the nocebo effect is a negative reaction caused by anxiety, which acts as a confounding factor. Different outcomes may be obtained depending upon whether the placebo effect is evaluated in terms of objective or subjective responses. Correlation analyses of outcomes from various clinical trials indicate that placebo improves subjective response more effectively than objective parameters. Psychosocial care of patients is an important aspect of welfare, and a better understanding of the mechanism of the placebo effect will be helpful in this regard. Cognitive therapy is well known to be as efficacious as antidepressant medication for treating depression. Therefore, we studied the relationship between activity in the cerebral prefrontal area and counseling intervention. Aromatherapy is known to be effective to improve mood. We thus evaluated the influence of counseling on the efficacy of aromatherapy in healthy young women. Participants in a room filled with the fragrance of bergamot completed both a self-reported questionnaire (motivation, feeling of drowsiness and general fatigue) and multi-dimensional fatigue inventory-20 (MFI-20). Further, as an objective measure of changes in stress, blood flow in the inferior frontal cortex was evaluated by near-infrared spectroscopy (NIRS). MFI-20 showed that the combination of aromatherapy with counseling significantly improved both brain activity and motivation, as compared to aromatherapy alone, though the self-reported questionnaire showed no significant difference. Regional blood flow in the inferior frontal cortex was significantly decreased by exposure to aromatherapy with counseling, compared to aromatherapy alone (p<0.05). The value of the NIRS-derived laterality index (LI), which is considered to be a measure of stress, was decreased by aromatherapy with counseling. Thus, we confirmed that the combination of aromatherapy with counseling intervention significantly improved mood and stress. Our results also demonstrated that counseling intervention increased the effectiveness of aromatherapy.

【胎盤-生理から病態へ-】胎盤シンシチオトロフォブラストにおける物質輸送機構

登美斉俊

産婦人科の実際 (金原出版(株)) 62 ( 8 ) 1041 - 1046 2013.08

ISSN 0558-4728

IFPA Meeting 2012 Workshop Report II: Epigenetics and imprinting in the placenta, growth factors and villous trophoblast differentiation, role of the placenta in regulating fetal exposure to xenobiotics during pregnancy, infection and the placenta

Ahmed M.S., Aleksunes L.M., Boeuf P., Chung M.K., Daoud G., Desoye G., Díaz P., Golos T.G., Illsley N.P., Kikuchi K., Komatsu R., Lao T., Morales-Prieto D.M., Nanovskaya T., Nobuzane T., Roberts C.T., Saffery R., Tamura I., Tamura K., Than N.G., Tomi M., Umbers A., Wang B., Weedon-Fekjaer M.S., Yamada S., Yamazaki K., Yoshie M., Lash G.E.

Placenta (Placenta) 34 ( SUPPL ) 6 - 10 2013.03

Article, review, commentary, editorial, etc. (international conference proceedings), ISSN 0143-4004

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology: 1) epigenetics and imprinting in the placenta; 2) growth factors and villous trophoblast differentiation; 3) role of the placenta in regulating fetal exposure to xenobiotics during pregnancy; 4) infection and the placenta.

Access to Document (DOI)

組織関門トランスポーターを介した薬物組織分布の制御

登美斉俊

DMPK ニュースレター (日本薬物動態学会) 26 ( 1 ) 17 - 21 2011.02

Article, review, commentary, editorial, etc. (scientific journal), Single Work

Blood-Retinal Barrier Transporters : Physiological Function and Drug Transport

TOMI Masatoshi

Journal of Pharmaceutical Science and Technology, Japan (The Academy of Pharmaceutical Science and Technology, Japan) 69 ( 6 ) 430 - 434 2009.11

Article, review, commentary, editorial, etc. (scientific journal), Single Work, ISSN 0372-7629

血液脳関門のclaudin-5制御による脳へのドラッグデリバリーは可能か?

登美斉俊

ファルマシア ((公社)日本薬学会) 40 ( 2 ) 165 - 166 2004.02

Book review, literature introduction, etc., ISSN 0014-8601

網膜を標的としたドラッグデリバリー

登美斉俊

薬剤学 ((公社)日本薬剤学会) 63 ( 4 ) 193 - 196 2003.11

Article, review, commentary, editorial, etc. (scientific journal), ISSN 0372-7629

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