Yuichi Sugiyama Distinguished Adjunct Professor
Degree : Affiliation : Position : Honor : Final education : Graduate School : Tel : Fax : Office : Add : Email :y-sugiyama@jiu.ac.jp Research Group: Group Website: Research Area:Pharmacology

Education Background

  • 1967-1971, University of Tokyo, Japan, B.S.Pharmacy
  • 1971-1973, University of Tokyo, Japan, M.S.
  • 1973-1978, University of Tokyo, Ph.D.

Working Experience

  • 1974-1988, Faculty of Pharmaceutical Sciences, Uiversity of Tokyo, Research Associate
  • 1979-1981, School of Medicine, UCLA, CA USA, Post-doc
  • 1989-1991, Faculty of Pharmaceutical Sciences, University of Tokyo, Associate Professor
  • 1991-2012, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Professor
  • 2012-2021, Cluster for Science, RIKEN, Yokohama, Japan, Head of Sugiyama Laboratory
  • 2021--present, Innovation base, Josai International University, Tokyo,Japan, Distinguished Professor
  • 2022-present, iHuman institute, ShaghaiTech University, China, Adjunct Professor

Research Interests

    Dr.Sugiyama’s major research interests include the followings:

1.         Physiologically based pharmacokinetics(PBPK):  Prediction of drug disposition (distribution, metabolism, elimination) from in vitro biochemical data.

2.         Kinetic and biochemical analysis of hepatic and renal clearance and transport of drugs

3.         Molecular and cell biological analysis of the mechanism for drug transport into the liver, kidney and brain (including a PET imaging based analysis)

4.         Quatitative prediction of tansporter and enzyme mediated drug-drug interaction based on in vitro studies

5.         Analyses of molecular target mediated drug disposition (TMDD) to predict the target occupancy in early phase of drug development

6.         Analysis of interindividual differences in the clearance of drugs which undergo transporter-mediated GI absorption, elimination and hepatic clearance

In the realm of new drug discovery and development, optimizing the ADME properties of a compound is crucial for enhancing its pharmacological effects while minimizing potential toxicity. Within the ADME processes, drug metabolizing enzymes and transporters play significant roles. This optimization is particularly critical during the lead optimization process, which occurs before entering the clinical Phase 1 study.

In today's research landscape, it is essential for scientists to shift their focus towards optimizing pharmacokinetics, considering factors such as drug-drug interactions (DDI) and interindividual variability. These considerations hold equal importance alongside the identification of the molecular target and lead compound.To support these efforts, the utilization of physiologically based pharmacokinetic (PBPK) modeling proves highly valuable. PBPK modeling allows for the extrapolation of in vitro information to in vivo outcomes. By incorporating PBPK modeling into our research, we can make significant contributions to our mission of developing methodologies that expedite the discovery of new drugs and enable the swift delivery of safe and effective therapies to patients.

Research Achievement

Dr. Sugiyama is acknowledged as a world-leader in the fields of physiologically based pharmacokinetics (PBPK) and membrane transporters. His work on PBPK has been pivotal for quantitative in vitro – in vivo extrapolation, especially the development of models for the prediction of drug clearance and the magnitude of drug-drug interactions in humans. Further, his studies on membrane transporters, which encompass functional and kinetic characterization, and the impact of genetic variation, have been fundamental to our understanding of the role of transporters in drug disposition. Professor Sugiyama’s research on membrane transporters has yielded better understanding of the basic aspects of transport mechanisms. He has discovered several examples in which transporters play a major role in drug disposition. Moreover, his work has highlighted the importance of considering pharmacokinetic properties in drug development, using high-throughput screening methods to test large numbers of drug candidates synthesized by combinatorial chemistry. Detailed in vitro studies of transporters for the first time appear to predict transporter-mediated drug-drug interaction in vivo. Lastly, genetic variations in transporter genes are being identified in his laboratory that can account for inter-individual differences in drug disposition and drug action. Thus, he has produced a remarkable body of scientific work, with profound impact on how we understand and use drugs.

Taken together, his achievements brought profound change to the discovery and development of new drugs, and their regulation by government authorities. He is actively conducting more research to pursue his ultimate purpose, prediction of pharmacokinetics and pharmacodynamics in early phases of drug discovery and development. These research efforts will contribute to successful drug development and to delivering the right drugs to the right patients.

Representative Publications

Representative publications (2015-2023)

(A)   Original Articles

1.       Izumi S, Nozaki Y, Maeda K, Komori T, Takenaka O, Kusuhara H, 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).

2.       Tomaru A, Takeda-Morishita M, Maeda K, Banba H, Takayama K, Kumagai Y, Kusuhara H, Sugiyama Y. Effects of Cremophor El on the Absorption of Orally Administered Saquinavir and Fexofenadine in Healthy Subjects. Drug Metab Pharmacokinet Jun 30(3):221-6 (2015).

3.       Shingaki T, Hume WE, Takashima T, Katayama Y, Okauchi T, Hayashinaka E, Wada Y, Cui Y, Kusuhara H, Sugiyama Y, Watanabe Y. Quantitative Evaluation of mMate1 Function Based on Minimally Invasive Measurement of Tissue Concentration Using PET with [(11)C]Metformin in Mouse. Pharm Res,32(8):2538-47(2015).

4.       Tanaka Y, Kitamura Y, Maeda K, Sugiyama Y. 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).

5.       Yamashita S, Kataoka M, Suzaki Y, Imai H, Morimoto T, Ohashi K, Inano A, Togashi K, Mutaguchi K, Sugiyama Y. 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).


6.       Yeung CK, Yoshida K, Kusama M, Zhang H, Ragueneau-Majlessi I, Argon S, Li L, Chang P, Le CD, Zhao P, Zhang L, Sugiyama Y, Huang SM. Organ Impairment-Drug-Drug Interaction Database: A Tool for Evaluating the Impact of Renal or Hepatic Impairment and Pharmacologic Inhibition on the Systemic Exposure of Drugs. CPT Pharmacometrics Syst Pharmacol. 4(8):489-94 (2015).

7.       Fujita K, Yoshino E, Kawara K, Maeda K, Kusuhara H, Sugiyama Y,  Yokoyama T, Kaneta T,  Ishida H, Sasaki Y. A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer. Cancer Chemother Pharmacol 76(4): 793-801 (2015).

8.       Liu H, Yu N, Lu S, Ito S, Zhang X, Prasad B, He E, Lu X, Li Y, Wang F, Xu H, An G, Unadkat JD, Kusuhara H, Sugiyama Y, Sahi J. Solute Carrier Family of the Organic Anion-Transporting Polypeptides 1A2- Madin-Darby Canine Kidney II: A Promising In Vitro System to Understand the Role of Organic Anion-Transporting Polypeptide 1A2 in Blood-Brain Barrier Drug Penetration. Drug Metab Dispos 43(7): 1008-1018 (2015).


9.       Haraya K, Kato M, Chiba K, Sugiyama Y. Prediction of Inter-Individual Variability on the Pharmacokinetics of Cyp1a2 Substrates in Non-Smoking Healthy Volunteers. Drug Metab Pharmacokinet 31: 276-84 (2016).


10.    Izumi S, Nozaki Y, Komori T, Takenaka O, Maeda K, Kusuhara H, Sugiyama Y. Investigation of Fluorescein Derivatives as Substrates of Organic Anion Transporting Polypeptide (OATP) 1B1 to Develop Sensitive Fluorescence-Based Oatp1B1 Inhibition Assays. Mol Pharm 13: 438-48 (2016).


11.    Kim SJ, Yoshikado T, Ieiri I, Maeda K, Kimura M, Irie S, Kusuhara H, Sugiyama Y. Clarification of the Mechanism of Clopidogrel-Mediated Drug-Drug Interaction in a Clinical Cassette Small-Dose Study and Its Prediction Based on in Vitro Information. Drug Metab Dispos 44: 1622-32 (2016).


12.    Kimura H, Yagi Y, Arimitsu K, Maeda K, Ikejiri K, Takano JI, Kusuhara H, Kagawa S, Ono M, Sugiyama Y, Saji H. Radiosynthesis of Novel Pitavastatin Derivative ([18 F]Ptv-F1) as a Tracer for Hepatic Oatp Using a One-Pot Synthetic Procedure. J Labelled Comp Radiopharm 59(13):565-575 (2016).


13.    Kishimoto W, Ishiguro N, Ludwig-Schwellinger E, Ebner T, Maeda K, Sugiyama Y. Usefulness of a Model-Based Approach for Estimating in Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay. J Pharm Sci 105(2):891-6 (2016).


14.    Ose A, Toshimoto K, Ikeda K, Maeda K, Yoshida S, Yamashita F, Hashida M, Ishida T, Akiyama Y, Sugiyama Y. Development of a Support Vector Machine-Based System to Predict Whether a Compound Is a Substrate of a Given Drug Transporter Using Its Chemical Structure. J Pharm Sci 105: 2222-30 (2016).


15.    Takano J, Maeda K, Bolger MB, Sugiyama Y. The Prediction of the Relative Importance of Cyp3a/P-Glycoprotein to the Nonlinear Intestinal Absorption of Drugs by Advanced Compartmental Absorption and Transit Model. Drug Metab Dispos 44(11):1808-18 (2016).


16.    Tsuruya Y, Kato K, Sano Y, Imamura Y, Maeda K, Kumagai Y, Sugiyama Y, Kusuhara H. Investigation of Endogenous Compounds Applicable to Drug - Drug Interaction Studies Involving the Renal Organic Anion Transporters, Oat1 and Oat3, in Humans. Drug Metab Dispos 44(12):1925-1933 (2016).


17.    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).


18.    Ito M, Kusuhara H, Ose A, Kondo T, Tanabe K, Nakayama H, Horita S, Fujita T, Sugiyama Y. Pharmacokinetic Modeling and Monte Carlo Simulation to Predict Interindividual Variability in Human Exposure to Oseltamivir and Its Active Metabolite, Ro 64-0802.AAPS J. 19(1):286-297 (2017).


19.    Izumi S, Nozaki Y, Komori T, Takenaka O, Maeda K, Kusuhara H, Sugiyama Y. 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 106(9):2678-2687 (2017).


20.    Kashihara Y, Ieiri I, Yoshikado T, Maeda K, Fukae M, Kimura M, Hirota T, Matsuki S, Irie S, Izumi N, Kusuhara H, Sugiyama Y. Small-dosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1 and ABCG2), and Interaction (Atorvastatin and Grapefruit Juice) Profiles of Five Probes for OATP2B1 and BCRP. J Pharm Sci106(9):2688-2694 (2017)


21.    Toshimoto K, Tomaru A, Hosokawa M, Sugiyama Y. Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects. Pharm Res. 34(8):1584-1600 (2017).


22.    Chiba K, Shimizu K, Kato M, Miyazaki T, Nishibayashi T, Terada K, Sugiyama Y. Estimation of inter-individual variability of pharmacokinetics of CYP2C9 substrates in humans. J Pharm Sci. 106(9):2695-2703 (2017).


23.    Kanamitsu K, Kusuhara H, Schuetz JD, Takeuchi K, Sugiyama Y. Investigation of the Importance of Multidrug Resistance-Associated Protein 4 (Mrp4/Abcc4) in the Active Efflux of Anionic Drugs Across the Blood-Brain Barrier. J Pharm Sci.  106(9):2566-2575 (2017).


24.    Fukuchi Y, Toshimoto K, Mori T, Kakimoto K, Tobe Y, Sawada T, Asaumi R, Iwata T, Hashimoto Y, Nunoya KI, Imawaka H, Miyauchi S, Sugiyama Y. Analysis of Nonlinear Pharmacokinetics of a Highly Albumin-Bound Compound: Contribution of Albumin-Mediated Hepatic Uptake Mechanism. J Pharm Sci. 106(9):2704-2714 (2017).


25.    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).


26.    Sugiyama Y, Maeda K, Toshimoto K.Is Ethnic Variability in the Exposure to Rosuvastatin Explained Only by Genetic Polymorphisms in OATP1B1 and BCRP or Should the Contribution of Intrinsic Ethnic Differences in OATP1B1 Be Considered? J Pharm Sci. 106(9):2227-2230 (2017).


27.    Kim SJ, Toshimoto K, Yao Y, Yoshikado T, Sugiyama Y. Quantitative Analysis of Complex Drug-Drug Interactions Between Repaglinide and Cyclosporin A/Gemfibrozil Using Physiologically Based Pharmacokinetic Models With In Vitro Transporter/Enzyme Inhibition Data. J Pharm Sci. 106(9):2715-2726 (2017).


28.    Toshimoto K, Tomoda Y, Chiba K, Sugiyama Y. Analysis of the Change in the Blood Concentration-Time Profile Caused by Complex Drug-Drug Interactions in the Liver Considering the Enterohepatic Circulation: Examining Whether the Inhibition Constants for Uptake, Metabolism, and Biliary Excretion Can be Recovered by the Analyses Using Physiologically Based Pharmacokinetic Modeling. J Pharm Sci. 106(9):2727-2738 (2017).


29.    Yoshikado T, Maeda K, Furihata S, Terashima H, Nakayama T, Ishigame K, Tsunemoto K, Kusuhara H, Furihata KI, Sugiyama Y. A Clinical Cassette Dosing Study for Evaluating the Contribution of Hepatic OATPs and CYP3A to Drug-Drug Interactions. Pharm Res. 34(8):1570-1583 (2017).


30.    Yoshikado T, Maeda K, Kusuhara H, Furihata KI, Sugiyama Y. Quantitative Analyses of the Influence of Parameters Governing Rate-Determining Process of Hepatic Elimination of Drugs on the Magnitudes of Drug-Drug Interactions via Hepatic OATPs and CYP3A Using Physiologically Based Pharmacokinetic Models. J Pharm Sci. 106(9):2739-2750 (2017).


31.    Takano H, Ito S, Zhang X, Ito H, Zhang MR, Suzuki H, Maeda K, Kusuhara H, Suhara T, Sugiyama Y. Possible Role of Organic Cation Transporters in the Distribution of [11C]Sulpiride, a Dopamine D2 Receptor Antagonist. J Pharm Sci. 106(9):2558-2565 (2017).


32.    Takehara I, Terashima H, Nakayama T, Yoshikado T, Yoshida M, Furihata K, Watanabe N, Maeda K, Ando O, Sugiyama Y, Kusuhara H. Investigation of Glycochenodeoxycholate Sulfate and Chenodeoxycholate Glucuronide as Surrogate Endogenous Probes for Drug Interaction Studies of OATP1B1 and OATP1B3 in Healthy Japanese Volunteers. Pharm Res. 34(8):1601-1614 (2017).


33.    Kusuhara H, Takashima T, Fujii H, Takashima T, Tanaka M, Ishii A, Tazawa S, Takahashi K, Takahashi K, Tokai H, Yano T, Kataoka M, Inano A, Yoshida S, Hosoya T, Sugiyama Y, Yamashita S, Hojo T, Watanabe Y. Comparison of pharmacokinetics of newly discovered aromatase inhibitors by a cassette microdosing approach in healthy Japanese subjects.Drug Metab Pharmacokinet. 32(6):293-300 (2017).


34.    Haraya K, Kato M, Chiba K, Sugiyama Y. Prediction of inter-individual variability on the pharmacokinetics of CYP2C8 substrates in human.Drug Metab Pharmacokinet. 32(6):277-285 (2017).


35.    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).


36.    Takano J, Maeda K, Kusuhara H, Sugiyama Y. Organic anion transporting polypeptide 1a4 is responsible for the hepatic uptake of cardiac glycosides in mice.Drug Metab Dispos. 46(5):652-657 (2018).


37.    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).


38.   Sato M, Toshimoto K, Tomaru A, Yoshikado T, Tanaka Y, Hisaka A, Lee W, Sugiyama Y. Physiologically Based Pharmacokinetic Modeling of Bosentan Identifies the Saturable Hepatic Uptake as A Major Contributor to Its Nonlinear Pharmacokinetics.Drug Metab Dispos. 46(5):740-748 (2018).


39.    Kaneko K, Tanaka M, Ishii A, Katayama Y, Nakaoka T, Irie S, Kawahata H, Yamanaga T, Wada Y, Miyake T, Toshimoto K, Maeda K, Cui Y, Enomoto M, Kawamura E, Kawada N, Kawabe J, Shiomi S, Kusuhara H, Sugiyama Y, Watanabe Y. A clinical quantitative evaluation of hepatobiliary transport of [11C]Dehydropravastatin in humans using positron emission tomography.Drug Metab Dispos. 46(5):719-728 (2018).


40.    Yao Y, Toshimoto K, Kim SJ, Yoshikado T, Sugiyama Y. Quantitative Analysis of Complex Drug-Drug Interactions between Cerivastatin and Metabolism/Transport Inhibitors Using Physiologically Based Pharmacokinetic Modeling. Drug Metab Dispos. 46(7):924-933 (2018).


41.    Kanda K, Takahashi R, Yoshikado T, Sugiyama Y. Total hepatocellular disposition profiling of rosuvastatin and pitavastatin in sandwich-cultured human hepatocytes. Drug Metab Pharmacokinet. 33(3):164-172 (2018).


42.    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).  Published Erratum:Mol Pharm. 17(2):722-723. (2020).


43.   Takehara I, Yoshikado T, Ishigame K, Mori D, Furihata KI, Watanabe N, Ando O, Maeda K, Sugiyama Y, Kusuhara H. Comparative Study of the Dose-Dependence of OATP1B Inhibition by Rifampicin Using Probe Drugs and Endogenous Substrates in Healthy Volunteers. Pharm Res. 35(7):138(2018).


44.   Nakamura T, Toshimoto K, Lee W, Imamura CK, Tanigawara Y, Sugiyama Y. Application of PBPK Modeling and Virtual Clinical Study Approaches to Predict the Outcomes of CYP2D6 Genotype-Guided Dosing of Tamoxifen.CPT Pharmacometrics Syst Pharmacol. 7(7):474-482 (2018).


45.   Wakayama N, Toshimoto K, Maeda K, Hotta S, Ishida T, Akiyama Y, Sugiyama Y. In Silico Prediction of Major Clearance Pathways of Drugs among 9 Routes with Two-Step Support Vector Machines.Pharm Res. 35(10):197 (2018).


46.   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).


47.   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).


48.   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).


49.   Mori D, Kashihara Y, Yoshikado T, Kimura M, Hirota T, Matsuki S, Maeda K, Irie S, Ieiri I, Sugiyama Y, Kusuhara H. Effect of OATP1B1 genotypes on plasma concentrations of endogenous OATP1B1 substrates and drugs, and their association in healthy volunteers. Drug Metab Pharmacokinet. 34(1):78-86 (2019).


50.   Takehara I, Yoshikado T, Ishigame K, Mori D, Furihata KI, Watanabe N, Ando O, Maeda K, Kusuhara H, Sugiyama Y. Correction to: Comparative Study of the Dose-Dependence of OATP1B Inhibition by Rifampicin Using Probe Drugs and Endogenous Substrates in Healthy Volunteers. Pharm Res. 36(4):55 (2019).


51.   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. 8(6):396-406 (2019).


52.   Maeda K, Ohnishi A, Sasaki M, Ikari Y, Aita K, Watanabe Y, Kusuhara H, Sugiyama Y, Senda M. Quantitative investigation of hepatobiliary transport of [11C]telmisartan in humans by PET imaging. Drug Metab Pharmacokinet. 34(5):293-299 (2019).


53.   Asaumi R, Menzel K, Lee W, Nunoya KI, Imawaka H, Kusuhara H, Sugiyama Y. Expanded Physiologically-Based Pharmacokinetic Model of Rifampicin for Predicting Interactions With Drugs and an Endogenous Biomarker via Complex Mechanisms Including Organic Anion Transporting Polypeptide 1B Induction. CPT Pharmacometrics Syst Pharmacol. 8(11):845-857 (2019).


54.   Lee N, Maeda K, Fukizawa S, Ieiri I, Tomaru A, Akao H, Takeda K, Iwadare M, Niwa O, Masauji T, Yamane N, Kajinami K, Kusuhara H, Sugiyama Y. Microdosing clinical study to clarify pharmacokinetic and pharmacogenetic characteristics of atorvastatin in Japanese hypercholesterolemic patients.Drug Metab Pharmacokinet. 34(6):387-395 (2019).


55.   Mori D, Kimoto E, Rago B, Kondo Y, King-Ahmad A, Ramanathan R, Wood LS, Johnson JG, Le VH, Vourvahis M, Rodrigues AD, Muto C, Furihata K, Sugiyama Y, Kusuhara H. Dose-Dependent Inhibition of OATP1B by Rifampicin in Healthy Volunteers: Comprehensive Evaluation of Candidate Biomarkers and OATP1B Probe Drugs. Clin Pharmacol Ther. 107(4):1004-1013 (2020).


56.   Nakaoka T, Uetake Y, Kaneko KI, Niwa T, Ochiai H, Irie S, Suezaki Y, Otsuka N, Hayashinaka E, Wada Y, Cui Y, Maeda K, Kusuhara H, Sugiyama Y, Hosoya T, Watanabe Y. Practical Synthesis of [18F]Pitavastatin and Evaluation of Hepatobiliary Transport Activity in Rats by Positron Emission Tomography. nabe Y. Mol Pharm. 17(6):1884-1898. (2020).


57.   Lee W, Koyama S, Morita K, Kiriake A, Kikuchi R, Chu X, Lee N, Scialis RJ, Shen H, Kimoto E, Tremaine L, Ishiguro N, Lotz R, Maeda K, Kusuhara H, Sugiyama Y.  Cell-to-Medium Concentration Ratio Overshoot in the Uptake of Statins by Human Hepatocytes in Suspension, but Not in Monolayer: Kinetic Analysis Suggesting a Partial Loss of Functional OATP1Bs. AAPS J. 22(6):133 (2020).

58. Aoki Y, Hayami K, Toshimoto K, Sugiyama Y. Cluster Gauss–Newton method; An algorithm for finding multiple approximate minimisers of nonlinear least squares problems with applications to parameter estimation of pharmacokinetic models. Optimization and Engineering (2020)  https://doi.org/10.1007/s11081-020-09571-2


59.   Miyake T, Kimoto E, Luo L, Mathialagan S, Horlbogen LM, Ramanathan R, Wood LS, Johnson JG, Le VH, Vourvahis M, Rodrigues AD, Muto C, Furihata K, Sugiyama Y, Kusuhara H. Identification of appropriate endogenous biomarker for risk assessment of multidrug and toxin extrusion protein-mediated drug-drug interactions in healthy volunteers. Clin Pharmacol Ther. 109(2):507-516 (2021).


60.   Park JE, Shitara Y, Lee W, Morita S, Sahi J, Toshimoto K, Sugiyama Y. Improved prediction of the drug-drug interactions of pemafibrate caused by cyclosporine A and rifampicin via PBPK modeling: Consideration of the albumin-mediated hepatic uptake of pemafibrate and inhibition constants with preincubation against OATP1B. J Pharm Sci. 110(1):517-528 (2021).


61.   Yoshikado T, Lee W, Toshimoto K, Morita K, Kiriake A, Chu X, Lee N, Kimoto E, Varma MVS, Kikuchi R, Scialis RJ, Shen H, Ishiguro N, Lotz R, Li AP, Kazuya M, Kusuhara H, Sugiyama Y. Evaluation of Hepatic Uptake of OATP1B Substrates by Short Term-Cultured Plated Human Hepatocytes: Comparison With Isolated Suspended Hepatocytes. J Pharm Sci.110(1):376-387 (2021).


62.   Tomaru A, Toshimoto K, Lee W, Ishigame K, Sugiyama Y. A Simple Decision Tree Suited for Identification of Early Oral Drug Candidates With Likely Pharmacokinetic Nonlinearity by Intestinal CYP3A Saturation. J Pharm Sci.110(1):510-516 (2021).


63.   Ito S, Lee W, Park JE, Yasunaga M, Mori A, Ohtsuki S, Sugiyama Y. Transient, Tunable Expression of NTCP and BSEP in MDCKII Cells for Kinetic Delineation of the Rate-Determining Process and Inhibitory Effects of Rifampicin in Hepatobiliary Transport of Taurocholate. J Pharm Sci. 110(1):365-375 (2021).


64.   Koyama S, Toshimoto K, Lee W, Aoki Y, Sugiyama Y. Revisiting nonlinear bosentan pharmacokinetics by PBPK modeling: Target binding, albeit not a major contributor to nonlinearity, can offer prediction of target occupancy. Drug Metab Dispos. 49(4):298-304 (2021).


65.   Asaumi R,  Nunoya KI, Yamaura Y, Taskar KS, Sugiyama Y. Robust physiologically based pharmacokinetic model of rifampicin for predicting drug–drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney   CPT Pharmacometrics Syst Pharmacol.;11:919–933 (2022)


66. Izumi S, Nozaki Y, Lee W, Sugiyama Y  Experimental and modeling evidence supporting the trans-inhibition mechanism for preincubation time-dependent, long-lasting inhibition of organic anion transporting polypeptide (OATP) 1B1 by cyclosporin A   Drug Metab Dispos  50: 541-551 (2022)


67.   Yoshikado T, Yasunori Aoki, Y,  Mochizuki T, Rodrigues D, Chiba K,Kusuhara H, Sugiyama Y:  Cluster Gauss-Newton method analyses of PBPK model parameter combinations of coproporphyrin-I  based on OATP1B-mediated rifampicin interaction  Studies.  CPT Pharmacometrics Syst Pharmacol.11:1341-1357(2022)


68.   Mochizuki T, Aoki Y,  Yoshikado T, Yoshida K,   Lai Y, Hirabayashi H, Yamaura Y, Rockich K, Taskar K, Takashima T, Chu X, Zamek-Gliszczynski MJ, Jialin Mao J, Maeda K, Furihata K, Sugiyama Y, Kusuhara H:  Physiologically-based pharmacokinetic model-based translation of OATP1B-mediated drug–drug  interactions from coproporphyrin I to probe drugs

Clin Transl Sci. 15:1519–1531 (2022).


69.   Mochizuki T, Zamek-Gliszczynski MJ, Yoshida K, Mao J, Taskar K, Hirabayashi H, Chu X, Lai Y, Takashima T, Rockich K, Yamaura Y, Fujiwara K, Mizuno T, Maeda K, Furihata K, Sugiyama Y, Kusuhara H Effect of Cyclosporin A and Impact of Dose Staggering on OATP1B1/1B3 Endogenous Substrates and Drug Probes for Assessing Clinical Drug Interactions. 

Clin Pharmacol Ther. 111(6):1315-1323 (2022)


70.   Nakaoka T, Kaneko KI, Irie S, Mawatari A, Igesaka A, Uetake Y, Ochiai H, Niwa T, Yamano E, Wada Y, Tanaka M, Kotani K, Kawahata H, Kawabe J, Miki Y, Doi H, Hosoya T, Kazuya M, Kusuhara H, Sugiyama Y, Watanabe Y  Clinical evaluation of [18F]pitavastatin for quantitative analysis of hepatobiliary transporter activity.

Drug Metab Pharmacokinet. 44: 100449 (2022)


71.   Maeda K, Takikawa H, Aiso M, Tsuji K, Kagawa T, Watanabe M, Sato K, Sakisaka S, Hiasa Y, Takei Y, Ohira H, Hashimoto E, Ayada M, Ikegami T, Arakawa N, Kusuhara H, Saito Y, Sugiyama Y. Frequency of null genotypes of glutathione S-transferase M1 and T1 in Japanese patients with drug-induced liver injury. Hepatol Res. 52(10):882-887 (2022)


72.    Cluster Gauss–Newton method An algorithm for fnding multiple approximate minimisers of nonlinear least squares problems with applications to parameter estimation of pharmacokinetic models Aoki Y, Hayami K, Toshimoto,  Sugiyama Y.  Optimization and Engineering 23:169–199 (2022)  https://doi.org/10.1007/s11081-020-09571-2


 Lee WI, Kim MS, Kim J, Aoki Y, Sugiyama Y  Predicting  in vivo Target Occupancy (TO) Profiles via PBPK-TO Modeling of Warfarin Pharmacokinetics in Blood: Importance of Low Dose Data and Prediction of Stereoselective Target Interactions https://doi.org/10.1124/dmd.122.000968



(B)   Review Articles

1         Y. Tanaka, Y. Kitamura, K. Maeda, Y. Sugiyama.Explication of Definitional Description and Empirical Use of Fraction of Orally Administered Drugs Absorbed From the Intestine (Fa) and Intestinal Availability (Fg): Effect of P-glycoprotein and CYP3A on Fa and Fg. J Pharm Sci. 105(2):431-42 (2016).


2         T. Burt, K. Yoshid, G. Lappin, L. Vuong, C. John, SN. de Wildt, Y. Sugiyama, M. Rowland. Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development. Clin Transl Sci. 9(2):74-88 (2016).


3         Y. Hayakawa, M. Kawada, H. Nishikawa, T. Ochiya, H. Saya, H. Seimiya, R. Yao, M. Hayashi, C. Kai, A. Matsuda, T. Naoe, A. Ohtsu, T. Okazaki, H. Saji, M. Sata, H. Sugimura, Y. Sugiyama, M. Toi, and T. Irimura. Report on the Use of Non-Clinical Studies in the Regulatory Evaluation of Oncology Drugs. Cancer Sci 107: 189-202. (2016).


4         Shitara Y, Sugiyama Y. Preincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions. Pharmacol Ther.177:67-80(2017).


5         Yahata M, Chiba K, Watanabe T, Sugiyama Y. Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma Concentration of Unbound Drugs, and Their Profiles for Substrates of Transporters. J Pharm Sci. 106(9):2345-2356 (2017).


6         Rodrigues AD, Taskar KS, Kusuhara H, Sugiyama Y. Endogenous Probes for Drug Transporters: Balancing Vision With Reality. Clin Pharmacol Ther.106(9):2345-2356 (2018).


7         Yee SW, Brackman DJ, Ennis EA, Sugiyama Y, Kamdem LK, Blanchard R, Galetin A, Zhang L, Giacomini KM. Influence of Transporter Polymorphisms on Drug Disposition and Response: A Perspective From the International Transporter Consortium. Clin Pharmacol Ther. 104(5):803-817 (2018).


8         Guo Y, Chu X, Parrott NJ, Brouwer KLR, Hsu V, Nagar S, Matsson P, Sharma P, Snoeys J, Sugiyama Y, Tatosian D, Unadkat JD, Huang SM, Galetin A; International Transporter Consortium. Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches.Clin Pharmacol Ther. 104(5):865-889. (2018).


9         Chu X, Liao M, Shen H, Yoshida K, Zur AA, Arya V, Galetin A, Giacomini KM, Hanna I, Kusuhara H, Lai Y, Rodrigues D, Sugiyama Y, Zamek-Gliszczynski MJ, Zhang L; International Transporter Consortium. Clinical Probes and Endogenous Biomarkers as Substrates for Transporter Drug-Drug Interaction Evaluation: Perspectives From the International Transporter Consortium. Clin Pharmacol Ther. 104(5):836-864 (2018).


10     Burt T, Vuong LT, Baker E, Young GC, McCartt AD, Bergstrom M, Sugiyama Y, Combes R. Phase 0, including microdosing approaches: Applying the Three Rs and increasing the efficiency of human drug development. Altern Lab Anim. 46(6):335-346 (2018).


11     Iwaki Y, Lee W, Sugiyama Y. Comparative and quantitative assessment on statin efficacy and safety: insights into inter-statin and inter-individual variability via dose- and exposure-response relationships.Expert Opin Drug Metab Toxicol. 15(11):897-911 (2019).


12     Yee SW, Do TP, Huang SM, Krauss RM, Kusuhara H, Sugiyama Y, Unadkat JD, Giacomini KM.Expanding Precompetitive Multisector Collaborations to Advance Drug Development and Pharmacogenomics.Clin Pharmacol Ther. 107(1):96-101 (2020).


13     Taskar KS, Pilla Reddy V, Burt H, Posada MM, Varma M, Zheng M, Ullah M, Emami Riedmaier A, Umehara KI, Snoeys J, Nakakariya M, Chu X, Beneton M, Chen Y, Huth F, Narayanan R, Mukherjee D, Dixit V, Sugiyama Y, Neuhoff S. Physiologically-Based Pharmacokinetic Models for Evaluating Membrane Transporter Mediated Drug-Drug Interactions: Current Capabilities, Case Studies, Future Opportunities, and Recommendations. Clin Pharmacol Ther. 107(5):1082-1115. (2020).


14     Zamek-Gliszczynski MJ, Patel M, Yang X, Lutz JD, Chu X, Brouwer KLR, Lai Y, Lee CA, Neuhoff S, Paine MF, Sugiyama Y, Taskar KS, Galetin A. Intestinal P-gp and Putative Hepatic OATP1B Induction: International Transporter Consortium Perspective on Drug Development Implications. Clin Pharmacol Ther. 109(1):55-64 (2021)


15     Lee W, Ha JM, Sugiyama Y.  Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion transporting polypeptides.

 J Biol Chem. 295(50):17349-17364 (2020).


16     Burt T, Young G, Lee W, Kusuhara H, Langer O, Rowland M, Sugiyama Y.  Phase 0/microdosing approaches: time for mainstream application in drug development?

Nat Rev Drug Discov. 19(11):801-818 (2020).


17     Zamek-Gliszczynski MJ, Patel M, Yang X, Lutz JD, Chu X, Brouwer KLR, Lai Y, Lee CA, Neuhoff S, Paine MF, Sugiyama Y, Taskar KS, Galetin A  Intestinal P-gp and Putative Hepatic OATP1B Induction: International Transporter Consortium Perspective on Drug Development Implications. Clin Pharmacol Ther. 2021 109(1):55-64 (2021)


18      Miyauchi S, Kim SJ, Lee W, Sugiyama Y. Consideration of albumin-mediated

    hepatic uptake for highly protein-bound anionic drugs: Bridging the gap of hepatic uptake clearance between in vitro and in vivo.Pharmacol Ther. Jun 24;107938. (2022).


19      Taskar KS, Yang X, Neuhoff S, Patel M, Yoshida K, Paine MF, Brouwer KLR, Chu X, Sugiyama Y, Cook J, Polli JW, Hanna I, Lai Y, Zamek-Gliszczynski M; ITCClinical Relevance of Hepatic and Renal P-gp/BCRP Inhibition of Drugs: An International Transporter Consortium Perspective.Clin Pharmacol Ther 112(3):573-592 (2022)


20     Zamek-Gliszczynski MJ, Sangha V, Shen H, Feng B, Wittwer MB, Varma MVS, Liang X, Sugiyama Y, Zhang L, Bendayan R; ITC  Transporters in Drug Development: International Transporter Consortium Update on Emerging Transporters of Clinical Importance.Clin Pharmacol Ther. 112(3):485-500 (2022) .



1.  Kazuya Maeda,Yuichi Sugiyama. Drug Transporters: Molecular Characterization and Role in Drug Disposition, Chapter 22, IN VITRO–IN VIVO SCALE-UP OF DRUG TRANSPORT ACTIVITIES,  Guofeng You and Marilyn E.Morris Eds  Wiley & Sons,Inc  https://doi.org/10.1002/9781119739883.ch22  (2022)

2. Giacomini KM and Sugiyama Y. Membrane transporters and drug response, Section 1, Chapter 4, in Goodman & Gilmans The Pharmacological Basis of Therapeutics, 14th Edition (Laurence L. Brunton, Bjorn C. Knollmann, Randa Hilal-Dandan eds) McGraw-Hill Companies, New York , pp. 79-100 (2023)



  • 1. Establishment of Evolutional Drug development with the Use of Microdosing Clinical Trial: Based on the Quantitative Prediction Technology of ADME, New Energy and Industrial Technology Development Organization, Japan, Project Leader (2008-2011)
  • 2. Mutitiplicity and Functional Analysis of Drug Transporters and Its Role in Drug Induced Side Effects, Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare for the Research on Advanced Medical Technology., Japan, Project Leader (2002-2004)
  • 3. Analysis of interindividual differences in drug response based on detoxification - and signal transduction systems in a research program for the establishment of personalized medicine, Advanced and Innovational Research Program in Life Sciences from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government, Project Leader (2002-2006)
  • 4. Strategic Approach to Drug Discovery and Development in Pharmaceutical Sciences, The 21st Century COE , Ministry of Education, Culture, Sports, Science and Technology, the Japanese GovernmentProgram, , Program Leader (2002-2006)
  • 5. Host Defense Mechanism - “Molecular Basis for the Xenobiotic Detoxification System, The Core Research for the Evolutional Science and Technology Program (CREST), Program Leader (1998-2002)


  • 1. 2020, Zuihochu Award “The Order of the Sacred Treasure, Gold Rays with Neck Ribbon.” given by the Government of Japan
  • 2. 2013, Honorary Doctor of Pharmacy, Uppsala Universitet
  • 3. 2013, Honorary Doctor of Science, honoris causa degree from the University of Florida.
  • 4. 2013, The ISSX R.T. Williams Distinguished Scientific Achievement Award
  • 5. 2012, B. Brodie Award from ASPET
  • 6. 2010, Medal with Purple Ribbon given by the Government of Japan
  • 7. 2009, FIP Host-Madsen Gold Medal
  • 8. 2008, ISSX Asian Pacific Scientific Achievement Award
  • 9. 2007, PSWC (Pharmaceutical Sciences World Conference) Research Achievement Award in 2007
  • 10. 2003, AAPS (American Association Pharmaceutical Scientists) Distinguished Pharmaceutical Scientist Award
  • 11. 2003, AAPS (American Association Pharmaceutical Scientists) Distinguished Pharmaceutical Scientist Award
  • 12. 2003, AAPS (American Association Pharmaceutical Scientists) Distinguished Pharmaceutical Scientist Award
  • 13. 2003, AAPS (American Association Pharmaceutical Scientists) Distinguished Pharmaceutical Scientist Award

Group Member

  • Name:Toshiaki Tsuchitani
    Position:Post-doctoral fellow
    Duration:July 2022~

Group Photo