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RIKEN Baton Zone Program Sugiyama Laboratory

Head of Sugiyama Laboratory: Yuichi Sugiyama (Ph.D.)

Research Summary

Yuichi  Sugiyama(Ph.D.)

Many drug candidate compounds are synthesized in the early stage of a drug discovery. For these drug candidates, binding affinities to the target molecule (related to pharmacodynamics), rates of metabolism and membrane transports (related to pharmacokinetics) will be studied using in vitro experiments. By comparing the various parameters obtained in these experiments, drug candidates will be selected and introduced into clinical trials. However, efficacies expected from animal experiments and in vitro experiments are not always reproducible in clinical trials, and it is also true that most of drug candidates drop out before the market. Since it costs much in clinical trials, it is very important to select good drug candidates before going to the stage of clinical trials. RIKEN established Sugiyama Laboratory to promote the construction of an integrated support system for efficient drug discovery. In Sugiyama Laboratory, we will establish a new methodology to select a reasonable drug candidates in the early stages of drug discovery. In particular, mathematical models that incorporate parameters obtained from a variety of in vitro screening will be constructed, which can be used for the quantitative simulation of pharmacokinetics and pharmacodynamics. Thus, before entering the clinical trials, we will accurately predict the efficacy of each drug candidate in human. In addition, PET molecular imaging which enables the real-time and non-invasive quantification of PET-probed drugs and drug candidates in organs should be useful for the optimization of our mathematical models. In the future, our research will lead to the development of drugs that have wide therapeutic ranges or that can be less affected by drug-drug interactions, inter-individual variation and disease states.

Main Research Fields

  • Medicine, Dentistry & Pharmacy

Related Research Fields

  • Complex Systems
  • Biological Sciences

Keywords

  • Transporter
  • Drug metabolism and pharmacokinetics
  • Pharmacokinetics/pharmacodynamics
  • Genetic polymorphism/ Personalized medicine
  • Drug interaction

Selected Publications

  • 1.Yoshikado T, Yoshida K, Kotani N, Nakada T, Asaumi R, Toshimoto K, Maeda K, Kusuhara H, Sugiyama Y.:
    "Quantitative Analyses of Hepatic OATP-Mediated Interactions Between Statins and Inhibitors Using PBPK Modeling With a Parameter Optimization Method"
    Clin Pharmacol Ther 100 (5):513-523 (2016).
  • 2.S. Izumi, Y. Nozaki, T. Komori, O. Takenaka, K. Maeda, H. Kusuhara, Y. Sugiyama.:
    "Comparison of the Predictability of Human Hepatic Clearance for Organic Anion Transporting Polypeptide Substrate Drugs Between Different In Vitro-In Vivo Extrapolation Approaches"
    J Pharm Sci 24 pii: (17):30084-9 (2017).
  • 3.Yoshikado T, Toshimoto K, Nakada T, Ikejiri K, Kusuhara H, Maeda K, Sugiyama Y.:
    "Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins"
    Drug Metab Dispos. 45(7):779-789 (2017).
  • 4.Miyauchi S, Masuda M, Kim SJ, Tanaka Y, Lee KR, Iwakado S, Nemoto M, Sasaki S, Shimono K, Tanaka Y, Sugiyama Y.:
    "The Phenomenon of Albumin-Mediated Hepatic Uptake of Organic Anion Transport Polypeptide Substrates: Prediction of the In Vivo Uptake Clearance from the In Vitro Uptake by Isolated Hepatocytes Using a Facilitated-Dissociation Model."
    Drug Metab Dispos. 46(3):259-267 (2018)
  • 5.Asaumi R, Toshimoto K, Tobe Y, Hashizume K, Nunoya KI, Imawaka H, Lee W, Sugiyama Y.:
    "Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug-Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects."
    CPT Pharmacometrics Syst Pharmacol.7(3):186-196 (2018)
  • 6.Izumi S, Nozaki Y, Kusuhara H, Hotta K, Mochizuki T, Komori T, Maeda K, Sugiyama Y.:
    "Relative Activity Factor (RAF)-Based Scaling of Uptake Clearance Mediated by Organic Anion Transporting Polypeptide (OATP) 1B1 and OATP1B3 in Human Hepatocytes."
    Mol Pharm. 15(6):2277-2288 (2018)
  • 7.Yoshikado T, Toshimoto K, Maeda K, Kusuhara H, Kimoto E, Rodrigues AD, Chiba K, Sugiyama Y.:
    "PBPK Modeling of Coproporphyrin I as an Endogenous Biomarker for Drug Interactions Involving Inhibition of Hepatic OATP1B1 and OATP1B3."
    CPT Pharmacometrics Syst Pharmacol. 7(11):739-747 (2018).
  • 8.Fujino R, Hashizume K, Aoyama S, Maeda K, Ito K, Toshimoto K, Lee W, Ninomiya SI, Sugiyama Y.:
    "Strategies to improve the prediction accuracy of hepatic intrinsic clearance of three antidiabetic drugs: Application of the extended clearance concept and consideration of the effect of albumin on CYP2C metabolism and OATP1B-mediated hepatic uptake."
    Eur J Pharm Sci. 125:181-192 (2018).
  • 9.Kim SJ, Lee KR, Miyauchi S, Sugiyama Y.:
    "Extrapolation of In Vivo Hepatic Clearance from In Vitro Uptake Clearance by Suspended Human Hepatocytes for Anionic Drugs with High Binding to Human Albumin: Improvement of In Vitro-to-In Vivo Extrapolation by Considering the "Albumin-Mediated"
    Hepatic Uptake Mechanism on the Basis of the "Facilitated-Dissociation Model". Drug Metab Dispos. 47(2):94-103 (2019).
  • 10.Nishiyama K, Toshimoto K, Lee W, Ishiguro N, Bister B, Sugiyama Y.:
    "Physiologically-Based Pharmacokinetic Modeling Analysis for Quantitative Prediction of Renal Transporter-Mediated Interactions Between Metformin and Cimetidine."
    CPT Pharmacometrics Syst Pharmacol. 2019 Feb 28. doi:10.1002/psp4.12398. [Epub ahead of print]

Related Links

Lab Members

Principal investigator

Yuichi Sugiyama
Head of Sugiyama Laboratory

Core members

Satoshi Koyama
Research Scientist
Kota Toshimoto
Postdoctoral Researcher
Atsuko Tomaru
Visiting Scientist
Hisako Motokawa
Technical Staff II
Sachie Satoh
Assistant
Aya Sonobe
Assistant
Aya Miyamoto
Research Part-time Worker II
Yukio Kato
Senior Visiting Scientist
Akihiro Hisaka
Senior Visiting Scientist
Kazuya Maeda
Senior Visiting Scientist
Kiyomi Ito
Visiting Scientist
Ichiro Ieiri
Visiting Scientist
Fumiyoshi Yamashita
Visiting Scientist
Maki Yoneko
Visiting Scientist
Hiroyuki Kusuhara
Visiting Scientist
Seiji Miyauchi
Visiting Scientist
Koji Chiba
Visiting Scientist
Katsuhisa Inoue
Visiting Scientist
Kousei Ito
Visiting Scientist
Takashi Yoshikado
Visiting Scientist
Soo-Jin Kim
Visiting Scientist
Masashi Honma
Visiting Scientist
Chiyo Imamura
Visiting Scientist
Yasunori Aoki
Visiting Scientist
Wooin Lee
Visiting Scientist
Nora Khayoung Lee
Visiting Scientist
Sumio Ohtsuki
Visiting Scientist
Akina Takami
Visiting Scientist
Ji Eun Park
Visiting Scientist
Katsuhiro Kanda
Visiting Scientist

Contact Information

1-7-22 Suehiro-cho, Tsurumi-ku
Yokohama, Kanagawa
230-0045, Japan
Tel: +81-(0)45-503-9210
Fax: +81-(0)45-506-9190

Email: ychi.sugiyama [at] riken.jp

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