Centers & Labs

RIKEN Innovation Center

Sugiyama Laboratory

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

Pharmacology & Toxicology

Related Research Fields

Biology & Biochemistry / Clinical Medicine / Computer Science

Research Subjects

  • In vitro - in vivo extrapolation (IVIVE) of pharmacokinetic parameters
  • Prediction of drug-drug interaction (DDI)
  • Evaluation of interindividual variability in pharmacokinetics and pharmacodynamics
  • Establishment of criteria on which exploratory investigational new drug clinial studies (eIND), microdose (MD) clinical studies and molecular imaging clinical studies should be performed

Selected Publications

  1. Yoshida K, Maeda K and Sugiyama Y.:
    “Hepatic and intestinal drug transporters: prediction of pharmacokinetic effects caused by drug-drug interactions and genetic polymorphisms.”
    Annu Rev Pharmacol Toxicol. ;53: 581-612 (2013).
  2. Izumi S, Nozaki Y, Komori T, Maeda K, Takenaka O, Kusano K, Yoshimura T, Kusuhara H and Sugiyama Y.:
    “Substrate-dependent inhibition of organic anion transporting polypeptide 1B1: comparative analysis with prototypical probe substrates estradiol-17beta-glucuronide, estrone-3-sulfate, and sulfobromophthalein.”
    Drug Metab Dispos 41:1859-1866 (2013).
  3. Kato K, Mori H, Kito T, Yokochi M, Ito S, Inoue K, Yonezawa A, Katsura T, Kumagai Y, Yuasa H, Moriyama Y, Inui K, Kusuhara H and Sugiyama Y.:
    “Investigation of endogenous compounds for assessing the drug interactions in the urinary excretion involving multidrug and toxin extrusion proteins.”
    Pharm Res 31:136-147 (2014).
  4. Kodaira H, Kusuhara H, Fuse E, Ushiki J and Sugiyama Y.:
    “Quantitative investigation of the brain-to-cerebrospinal fluid unbound drug concentration ratio under steady-state conditions in rats using a pharmacokinetic model and scaling factors for active efflux transporters.”
    Drug Metab Dispos 42:983-989 (2014).
  5. Maeda K, Tian Y, Fujita T, Ikeda Y, Kumagai Y, Kondo T, Tanabe K, Nakayama H, Horita S, Kusuhara H and Sugiyama Y.:
    “Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT) 1 and OAT3 in humans.” Eur J Pharm Sci 59:94-103 (2014).
  6. Toshimoto K, Wakayama N, Kusama M, Maeda K, Sugiyama Y, Akiyama Y.:
    “In silico prediction of major drug clearance pathways by support vector machines with
    feature-selected descriptors.”
    Drug Metab Dispos 42(11):1811-9 (2014).
  7. Yamada A, Maeda K, Kiyotani K, Mushiroda T, Nakamura Y, Sugiyama Y.:
    “Kinetic Interpretation of the Importance of OATP1B3 and MRP2 in Docetaxel-Induced Hematopoietic Toxicity.”
    CPT Pharmacometrics Syst Pharmacol 3: e126 (2014)
  8. Izumi S, Nozaki Y, Maeda K, Komori T, Takenaka O, Kusuhara H and Sugiyama Y.:
    “Investigation of the Impact of Substrate Selection on In Vitro Organic Anion Transporting Polypeptide 1B1 Inhibition Profiles for the Prediction of Drug-Drug Interactions.”
    Drug Metab Dispos 43:235-247 (2015).
  9. Y. Tanaka, Y. Kitamura, K. Maeda, and Y. Sugiyama.:
    “Quantitative Analysis of the Abcg2 C.421c>a Polymorphism Effect on in Vivo Transport Activity of Breast Cancer Resistance Protein (Bcrp) Using an Intestinal Absorption Model.”
    J Pharm Sci104(9):3039-48 (2015).
  10. Yamashita, M. Kataoka, Y. Suzaki, H. Imai, T. Morimoto, K. Ohashi, A. Inano, K. Togashi, K. Mutaguchi, and Y. Sugiyama.:
    “An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.”
    J Pharm Sci 104(9):3154-61 (2015).

Lab Members

Principal Investigator

Yuichi Sugiyama
Head of Sugiyama Laboratory

Core Members

Takashi Yoshikado
Research Scientist
Aya Kiriake
Research Scientist
Kota Toshimoto
Postdoctoral Researcher
Kyeong Ryoon Lee
Visiting Scientist
Sae Hee Kim
Visiting Scientist
Insoo Yoon
Visiting Scientist
Atsuko Tomaru
Visiting Scientist
Kiyoe Morita
Technical Staff I
Keiko Ishigame
Technical Staff II
Hisako Motokawa
Technical Staff II
Sachie Satoh
Chinami Yamada
Aya Miyamoto
Part-time Worker
Rie Abe
Part-time Worker
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

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]

Related links