Welcome to
Sugiyama Laboratory
論文
最近７年間の主要な成果を、研究項目①~⑥に分類して示す
①：代謝・輸送過程の両方が関与する複雑な薬物間相互作用 (DDI),
動態の個体間変動 (PGx) の予測；拡張クリアランス理論およびPBPKモデルによる予測
2021年
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 (Review)
Clin Pharmacol Ther. 109(1):55-64 (2021).
2020年
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 (Review)
J Biol Chem. 295(50):17349-17364 (2020).
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).
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 (Review)
Clin Pharmacol Ther. 107(1):96-101 (2020).
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
2019年
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).
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).
2018年
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).
2017年
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)
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)
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).
2016年
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：内因性バイオマーカーを用いたより精度の高いDDI予測法の確立
2021年
2020年
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).
2019年
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).
2018年
Rodrigues, A. D., Taskar, K. S., Kusuhara, H. & Sugiyama, Y. Endogenous Probes for Drug Transporters: Balancing Vision With Reality.
Clin. Pharmacol. Ther. 103, 434–448 (2018).
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).
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).
➂：In vitro試験の結果を統合的に組み込んだIVIVE方法論の確立
（特に血漿タンパク結合の強い化合物）
2021年
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 (Review).
Pharmacol Ther. Jun 24;107938. (2021). Online ahead of print.
2020年
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).
2019年
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).
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).
2018年
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).
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).
2017年
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).
④：ヒトにおける薬物動態の個体間変動、病態時変動、年齢による変動 を予測可能にするvirtual clinical study に関する方法論の実施および検証
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)
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).
M. Ito, H. Kusuhara, A. Ose, T. Kondo, K. Tanabe, H. Nakayama, S. Horita, T. Fujita, Y. Sugiyama. 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)
S. J. Kim, T. Yoshikado, I. Ieiri, K. Maeda, M. Kimura, S. Irie, H. Kusuhara, and Y. Sugiyama. 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)
⑤：分子標的結合依存的な薬物体内動態（TMDD）の解析
⑥：探索的臨床試験、マイクロドース試験の必要性についての判断基準の確立
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).
J. Takano, K. Maeda, M. B. Bolger, and Y. Sugiyama. 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 44:1808-18:(2016)
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)