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YUASA Hiroaki

    Graduate School of Pharmaceutical Sciences Department of Biopharmaceutics　Professor
Contact： yuasaphar.nagoya-cu.ac.jp
Last Updated :2024/04/26

Researcher Information

Degree

  • Ph.D.（The University of Tokyo）

URL

J-Global ID

Profile

  • Research activities focused on biopharmaceutics (drug disposition studies)

    (1) Pharmacokinetic, physiological, and pathophysiological roles of transporters

    (2) Methodologies of evaluation and prediction of drug disposition

Research Interests

  • drug therapy   transporter   drug disposition   drug development   

Research Areas

  • Life sciences / Clinical pharmacy / Biopharmaceutics (drug diposition studies)

Academic & Professional Experience

  • 2002 - Today  Nagoya City UniversityGraduate School of Pharmaceutical SciencesProfessor
  • 2000 - 2002  Nagoya City UniversityFaculty of Pharmaceutical SciencesProfessor
  • 1992 - 2000  Nagoya City UniversityFaculty of Pharmaceutical SciencesAssociate Professor
  • 1991 - 1992  Nagoya City UniversityFaculty of Pharmaceutical SciencesSenior Assistant Professor
  • 1989 - 1991  The University of MichiganCollege of PharmacyPostdoctoral Fellow
  • 1986 - 1991  Nagoya City UniversityFaculty of Pharmaceutical SciencesAssistant Professor

Education

  • 1985 - 1986  The University of Tokyo  Graduate School of Pharmaceutical Sciences  Ph.D. Course
  • 1983 - 1985  The University of Tokyo  Graduate School of Pharmaceutical Sciences  M.S. Course (completed)
  • 1979 - 1983  The University of Tokyo  Faculty of Pharmaceutical Sciences (completed)

Association Memberships

  • American Society for Pharmacology and Experimental Therapeutics   International Society for the Study of Xenobiotics   International Pharmaceutical Federation   Controlled Release Society   American Association of Pharmaceutifical Scientists   Academy of Pharmaceutical Science and Technology, Japan   Japanese Society for the Study of Xenobiotics   Pharmaceutical Society of Japan   

Published Papers

Books etc

  • Drug absorption from the colon in situ
    Hiroaki Yuasa "Drug Absorption Studies: In Situ, In Vitro and In Silico Models" ed. by Carsten Ehrhardt and Kwang-Jin Kim, Springer, New York, NY, pp. 77 - 88 (Ch. 3) 2008
  • 消化管吸収の評価法
    湯浅 博昭 「分子薬物動態学」，杉山 雄一，楠原 洋之編，南山堂，東京，pp. 447 - 459（第24章） 2008
  • 消化管吸収性の予測:in vitroからin vivoへ
    湯浅 博昭 「薬物バイオアベイラビリティ評価と改善の科学：より良き医薬品開発のために」，杉山 雄一編，現代医療社，東京，pp. 229 - 245（第7章，第1部） 1998
  • 腸管吸収の予測:in vitroからin vivoへ
    湯浅 博昭 「ファーマコキネティクス研究の方法と技術」，日本薬物動態学会ワークショップ実行委員会編，日本薬物動態学会，東京，pp. 169 - 181（第8章） 1993
  • 薬物生体膜輸送のヒトへの外挿
    湯浅 博昭 「続医薬品の開発（第4巻）：薬物の生体膜輸送と組織標的化II」，寺田 弘，辻 彰編，廣川書店，東京，pp. 518 - 523（第5章，第8節） 1991

MISC

Industrial Property Rights

  • 特願2017-152034:小腸上皮細胞特異的な尿酸トランスポーター及びその利用  2017年/08/04
    湯浅 博昭, 保嶋 智也, 井上 勝央, 山本 俊輔

Awards & Honors

  • 1995 Japanese Society for the Study of Xenobiotics Young Investigator Award
     
    受賞者: Hiroaki Yuasa
  • 1993 Pharmaceutical Society of Japan (Tokai Chapter) Young Investigator Award
     
    受賞者: Hiroaki Yuasa

Research Grants & Projects

  • 新規ポリアミントランスポーターの機能及び生理的役割の解明
    日本学術振興会：科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 湯浅 博昭; 保嶋 智也; 山城 貴弘
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2013/04 -2016/03 
    Author : Yuasa Hiroaki; OHTA KINYA
     
    Aquaporin 10 was found to be capable of transporting major nucleobases (adenine，guanine，cytosine，thymine and uraci1), and also 5-fluorouracil and 6-mercaptopurine, which are drugs derived from nucleobases. The transport of those compounds was suggested not to be saturable, being mediated by its channel-like function. On the other hand, its operation could not be confirmed in the Caco-2 cell as an intestinal epithelial cell model. More detailed studies should be needed to further clarify the potential role of aquaporin 10 in the intestinal absorption of nucleobases and analogous drugs. It may also be needed to examine a possibility that the Caco-2 cell might not be suitable as a model to assess the transport of this class of compounds.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    Date (from‐to) : 2011 -2012 
    Author : YUASA Hiroaki; INOUE Katsuhisa; OHTA Kinya
     
    Functional characteristics of human vesicular organic anion transporter 1 (VOAT1) were examined by assessing the cellular uptake (accumulation in the endoplasmic reticulum) of 5-aminofluorescein (5-AF) as a fluorescent probe substrate, based on the observation of fluorescent microscopic images. 5-AF uptake was found to be specifically inhibited by several anti-allergic drugs, anti-inflammatory drugs, and endogenous fatty acids, including their oxidative products. These findings suggest that VOAT1 might be involved in the transport of lipid mediators and, thereby, play a role in inflammatoric and immunologic processes. It might also be involved in the pharmacologic action of anti-inflammatory drugs. Thus, we could obtain valuable information about the functional characteristics of VOAT1, although it needs to be further validated by quantitative assessments.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2008 -2010 
    Author : YUASA Hiroaki; INOUE KATSUHISA; OHTA Kinya
     
    Identification of the Na^+-dependent glycerol transporter, which was attempted by the expression cloning method and the bioinformatic approach using gene databases, was unsuccessful. But it was found that, interestingly, aquaglyceroporins can transport glycerol by a carrier-mediated type of mechanism. Although any of them is unlikely to be the molecular entity of the Na^+-dependent glycerol transporter, the finding would help identifying transporters involved in glycerol disposition and understanding their roles.
  • Molecular and Functional Characteristics of Glycerol Transporter in HCT-15 Cell Model
    Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2006 -2007 
    Author : YUASA Hiroaki; YAYOI Hayashi; KATSUHISA Inoue
     
    To clarify the molecular and functional characteristics of glycerol transporters, we conducted studies on a Na^+-dependent one in HCT-15 cells, particularly examining the effects on glycerol uptake of 1) cell differentiation induced by butyrate treatment and 2) several compounds structurally analogous to glycerol. Butyrate treatment brought about an approximately 5-fold increase in the maximum glycerol transport rate, without altering the Michaelis constant (affinity) significantly. Glycerol uptake in butyrate-treated cells was highly Na^+-dependent and specifically inhibited by some structurally analogous compounds as it was in untreated cells, indicating an induction of the Na^+-dependent glycerol transporter. Furthermore, this induction was almost completely suppressed by actinomycin D, an inhibitor of gene transcription, and cycloheximide, an inhibitor of protein synthesis. All these findings provide evidences for the presence of a specific transporter protein for glycerol. Among several compounds tested for their inhibitory effects on glycerol uptake, monoacetin and monobutyrin, which are ester type of glycerol derivatives, were found to be the most potent inhibitors. Because they inhibited glycerol uptake competitively, they may possibly be substrates of the glycerol transporter. This would suggest that glycerol ester derivatives of drugs might be delivered via the transporter. Interestingly, enantioselective characteristic was found for competitive inhibition, though relatively weak, by 1, 2-propanediol, where the S-(+)-enantiomer is favored by the transporter than the R-(-)-enantiomer. All these features are also characteristic of transport mediated by a specific transporter protein, providing additional evidences for the presence of such a specific transporter protein for glycerol. Thus, we could obtain several lines of evidences for the presence of a Na^+-dependent glycerol transporter in HCT-15 cells. This would help in identifying it and elucidating its transport mechanism and physiological role.
  • Novel Transporter Responsible for Intestinal Glycerol Absorption : Characterization of Its Function and Physiological Role
    Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2004 -2005 
    Author : YUASA Hiroaki; HAYASHI Yayoi; INOUE Katsuhisa
     
    The uptake of glycerol in the everted sacs of the rat small intestine was highly saturable, suggesting the involvement of carrier-mediated transport. Although moderate passive transport component was also observed, it was found that carrier-mediated transport is prevailing at concentrations far lower than the Michaelis constant, where carrier-mediated transport is in the linear phase and most efficient. The glycerol carrier was further suggested to be of Na^+-dependent and secondary active, and specific to glycerol and some analogous compounds. It should also be noted that carrier-mediated glycerol transport is highly efficient, being comparable to D-glucose transport by SGLT1(sodium-dependent glucose transporter 1), which is well known for its very high efficiency. These characteristics of carrier-mediated glycerol transport were consistent with those in the closed loop and the perfused segment of the rat small intestine in situ. Thus, we successfully demonstrated the presence of a carrier-mediated transport system specific to glycerol and some analogous compounds in the rat intestinal tissue, and characterized it kinetically. HCT-15 is a human colon cancer cell line, which was found to be able to perform Na^+-dependent glycerol uptake in the present research project. Although the glycerol carrier in HCT-15 cells was suggested to be different from the one in the small intestine as there was a 50-fold difference in the Michaelis constants, the profiles of inhibition of glycerol transport by various compounds were quite similar, indicating similar characteristics in recognition of substrates and/or inhibitors. Therefore, it maybe possible to use HCT-15 cells for screening inhibitors and potential substrates. HCT-15 could still be a useful model cell line for studies to identify a group of Na^+-dependent glycerol carriers and to elucidate their transport mechanism. Such carriers would be of interest as possible pathways of drug delivery and targets of drug development.
  • Pharmacokinetic and Cellular Biological Study on Colonic Absorption : Strategies for Optimized Controlled Release Oral Drug Delivery
    Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2000 -2002 
    Author : YUASA Hiroaki; INOUE Katsuhisa; HAYASHI Yayoi
     
    It was found in the rat that riboflavin transport in the colon is mediated by a Na^+dependent carrier-mediated transport system similar to one in the small intestine. The transport system in the colon was as efficient as one in the small intestine. It was also found that several tricyclic-type drugs analogous to riboflavin, such as chlorpromazine, specifically inhibit carrier-mediated riboflavin transport in both intestinal sites. Those inhibitors may include competitive substrates that could be transported, though it requires more detailed investigation. Furthermore, the riboflavin transport systems in both intestinal sites seemed to be quite similar in terms of recognition of substrates and inhibitors, though they might not be identical. For some other carrier-mediated transport systems examined, those of D-glucose and bile acids were found to be present in the colon, though far less efficient than the riboflavin transport system. Thus, the riboflavin transport system seemed to be most promising for utilization in oral drug delivery via colon. Drugs designed to fit the riboflavin carriers and as well absorbed from the colon as from the small intestine would be suitable for a sustained-release formulation that is effective even after reaching the colon. Drugs that are metabolized by CYP3A, such as cyclosporine, were found to be significantly metabolized at first-pass in the colon of rats as well as in the small intestine. Thus, in terms of metabolism by CYP3A, delivery via colon would not lead to any further reduction in bioavailability, compared with delivery via small intestine. However, the membrane permeability of cyclosporine, which is restricted by secretory transport by P-glycoprotein, was significantly lower in the colon than in the small intestine. Therefore, for those that undergo CYP3A metabolism and P-glycoprotein secretion, delivery via colon could lead to a reduction in the bioavailability.
  • 経口薬物吸収の生理機構論的解析
    日本学術振興会：科学研究費助成事業 奨励研究(A)
    Date (from‐to) : 1994 -1994 
    Author : 湯浅 博昭
     
    経口投与後の薬物の胃腸管内動態のモデル解析により,胃排出および腸管吸収の速度定数を推定する方法を考案した.腸管吸収速度定数は,さらに,腸管腔内容積,腸管膜透過性という二つの生理学的パラメーターにより記述される.解析方法の妥当性の確認を兼ねて,ラットにおいて,L-glucose(モデル薬物)の吸収に及ぼす投与液量,摂食条件(絶食,非絶食)の影響を検討した結果,投与液量の増大に伴う胃排出の促進と腸管吸収の低下,および絶食による腸管吸収の上昇が認められた.さらに,腸管吸収の変動は主として腸管腔内容積の変化によるものであり,腸管膜透過性には変化がないことが示された.今回の実験処置が腸管膜透過性に影響を及ぼす可能性は本来極めて小さいことから,解析方法の妥当性が確認されたものと判断した. 応用として,ラットにおいてD-xylose(腸管吸収機能検査薬)の経口吸収の加齢に伴う変化に関する解析を行い,吸収速度定数およびその決定因子としての胃排出,腸管腔内容積,腸管膜透過性に変化がないことを見出した.また,同時に,加齢に伴う吸収率の増大を認めたが,これは腸管通過の遅延によるものと考えられた. また,ラットでの麻酔下灌流法が腸管膜透過性の評価のためのモデル系として汎用されているが,麻酔条件により腸管膜透過性が変化することが示された.データの解釈ならびに上述のモデルに適用しての経口吸収の予測には注意を要すると考えられる.経口投与時(in vivo)における膜透過性との関係を明らかにし,補正方法等を考案することが,今後必要であろう.

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