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 guidelines for exploratory new drug studies (eIND), microdose (MD) clinical studies and molecular imaging clinical studies

Original Articles(2012~Present)

  1. Kanamitsu K, Nozaki Y, Nagaya Y, Sugiyama Y, Kusuhara H. Corrigendum to "Quantitative prediction of histamine H1 receptor occupancy by the sedative and non-sedative antagonists in the human central nervous system based on systemic exposure and preclinical data" Drug Metab Pharmacokinet (2017) In Press
  2. Sugiyama Y. Importance of Reverse Translational Research (rTR). Yakugaku Zasshi. 137(6):673-679 (2017)
  3. Rodrigues AD, Taskar KS, Kusuhara H, Sugiyama Y. Endogenous Probes for Drug Transporters: Balancing Vision with Reality. Clin Pharmacol Ther. (2017) In Press

  4. 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 (2017) In Press
  5. Yahata M, Chiba K, Watanabe T, Sugiyama Y. Possibility of predicting SERT occupancy from the in vitro inhibition constant for SERT, the clinically relevant plasma concentration of unbound drugs, and their profiles for substrates of transporters. J Pharm Sci (2017) In Press

  6. 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 (2017) In Press

  7. Yoshikado T, Kazuya M, 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 (2017) In Press

  8. 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 (2017) In Press

  9. 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 (2017) In Press

  10. Sugiyama Y, Kazuya M, 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 (2017) In Press

  11. 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 (2017) In Press

  12. 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 (2017) In Press

  13. 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 (2017) In Press
  14. 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 (2017) In Press
  15. 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 5 Probes for OATP2B1 and BCRP. J Pharm Sci (2017) In Press
    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 (2017) In Press
  16. 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 (2017) In Press
  17. Kanamitsu K, Nozaki Y, Nagaya Y, Sugiyama Y, Kusuhara H. Quantitative prediction of histamine H1 receptor occupancy by the sedative and non-sedative antagonists in the human central nervous system based on systemic exposure and preclinical data.  Drug Metab Pharmacokinet 32:135-144 (2017)
  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. AAPSJ19:286-97(2017)
  19. Kanamitsu K, Arakawa R, Sugiyama Y, Suhara T, Kusuhara H. Prediction of CNS occupancy of dopamine D2 receptor based on systemic exposure and in vitro experiments. Drug Metab Pharmacokinet 6:395-404(2016) 
  20. 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: 513-523 (2016)
  21. Y. Tsuruya, K. Kato, Y. Sano, Y. Imamura, K. Maeda, Y. Kumagai, Y. Sugiyama, and H. Kusuhara. 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 1925-33 (2016).
  22. Y. Tanaka, Y. Kitamura, K. Maeda, and 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: 431-42 (2016)
  23. 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)
  24. A. Ose, K. Toshimoto, K. Ikeda, K. Maeda, S. Yoshida, F. Yamashita, M. Hashida, T. Ishida, Y. Akiyama, and Y. Sugiyama. 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)
  25. W. Kishimoto, N. Ishiguro, E. Ludwig-Schwellinger, T. Ebner, K. Maeda, and Y. Sugiyama. Usefulness of a Model-Based Approach for Estimating in Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay. J Pharm Sci:105 891-6 (2016)
  26. H. Kimura, Y. Yagi, K. Arimitsu, K. Maeda, K. Ikejiri, J. I. Takano, H. Kusuhara, S. Kagawa, M. Ono, Y. Sugiyama, and H. Saji. 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:59 565-75 (2016).
  27. 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)
  28. S. Izumi, Y. Nozaki, T. Komori, O. Takenaka, K. Maeda, H. Kusuhara, and Y. Sugiyama, 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)
  29. K. Haraya, M. Kato, K. Chiba, and Y. Sugiyama. Prediction of Inter-Individual Variability on the Pharmacokinetics of Cyp1a2 Substrates in Non-Smoking Healthy Volunteers. Drug Metab Pharmacokinet 31: 276-84 (2016).
  30. Yagi Y, Kimura H, Arimitsu K, Ono M, Maeda K, Kusuhara H, Kajimoto T, Sugiyama Y and Saji H. The synthesis of [(18)F]pitavastatin as a tracer for hOATP using the Suzuki coupling. Org Biomol Chem 13(4):1113-21 (2015).
  31. 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).
  32. Liu, H., N. Yu, S. Lu, S. Ito, X. Zhang, B. Prasad, E. He, X. Lu, Y. Li, F. Wang, H. Xu, G. An, J. D. Unadkat, H. Kusuhara, Y. Sugiyama and J. Sahi. 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).
  33. Fujita, K., E. Yoshino, K. Kawara, K. Maeda, H. Kusuhara, Y. Sugiyama, T. Yokoyama, T. Kaneta, H. Ishida and Y. Sasaki. A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer. Cancer Chemother Pharmacol 76(4): 793-801 (2015).
  34. 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).
  35.  Y. Mano, Y. Sugiyama, and K. Ito. Use of a Physiologically Based Pharmacokinetic Model for Quantitative Prediction of Drug-Drug Interactions Via Cyp3a4 and Estimation of the Intestinal Availability of Cyp3a4 Substrates. J Pharm Sci 104(9):3183-93(2015).
  36. 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).

  37. K. Kato, C. Moriyama, N. Ito, X. Zhang, K. Hachiuma, N. Hagima, K. Iwata, J. Yamaguchi, K. Maeda, K. Ito, H. Suzuki, Y. Sugiyama, and H. Kusuhara. Involvement of Organic Cation Transporters in the Clearance and Milk Secretion of Thiamine in Mice. Pharm Res 32:2192-204 (2015) 

  38. 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).
  39. A. Tomaru, M. Takeda-Morishita, K. Maeda, H. Banba, K. Takayama, Y. Kumagai, H. Kusuhara, and Y. Sugiyama. 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). 
  40. Yagi Y, Kimura H, Arimitsu K, Ono M, Maeda K, Kusuhara H, Kajimoto T, Sugiyama Y and Saji H. The synthesis of [(18)F]pitavastatin as a tracer for hOATP using the Suzuki coupling. Org Biomol Chem 13:1113-1121 (2015).
  41. Ware JA, Urquhart BL, Sugiyama Y and Zamek-Gliszczynski MJ. Breast cancer resistance protein substrate and inhibition evaluation: why, when, and how? Drug Metab Dispos 42:1979-1980 (2014).
  42. Seki C, Oh-Nishi A, Nagai Y, Minamimoto T, Obayashi S, Higuchi M, Takei M, Furutsuka K, Ito T, Zhang MR, Ito H, Ito M, Ito S, Kusuhara H, Sugiyama Y and Suhara T. Evaluation of [(11)C]oseltamivir uptake into the brain during immune activation by systemic polyinosine-polycytidylic acid injection: a quantitative PET study using juvenile monkey models of viral infection. EJNMMI Res 4:24 (2014).
  43. Kitamura Y, Yoshida K, Kusama M and Sugiyama Y. A proposal of a pharmacokinetic/pharmacodynamic (PK/PD) index map for selecting an optimal PK/PD index from conventional indices (AUC/MIC, Cmax/MIC, and TAM) for antibiotics. Drug Metab Pharmacokinet (2014).
  44. Yi S, An H, Lee H, Lee S, Ieiri I, Lee Y, Cho JY, Hirota T, Fukae M, Yoshida K, Nagatsuka S, Kimura M, Irie S, Sugiyama Y, Shin DW, Lim KS, Chung JY, Yu KS and Jang IJ. Korean, Japanese, and Chinese populations featured similar genes encoding drug-metabolizing enzymes and transporters: a DMET Plus microarray assessment. Pharmacogenet Genomics 24:477-485 (2014).
  45. Chiba K, Shimizu K, Kato M, Nishibayashi T, Terada K, Izumo N and Sugiyama Y. Prediction of inter-individual variability in the pharmacokinetics of CYP2C19 substrates in humans. Drug Metab Pharmacokinet 29:379-386 (2014).
  46. 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).
  47. 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).
  48. Naoi S, Hayashi H, Inoue T, Tanikawa K, Igarashi K, Nagasaka H, Kage M, Takikawa H, Sugiyama Y, Inui A, Nagai T and Kusuhara H. Improved liver function and relieved pruritus after 4-phenylbutyrate therapy in a patient with progressive familial intrahepatic cholestasis type 2. J Pediatr 164:1219-1227.e1213 (2014).
  49. Imamura Y, Tsuruya Y, Damme K, Heer D, Kumagai Y, Maeda K, Murayama N, Okudaira N, Kurihara A, Izumi T, Sugiyama Y and Kusuhara H. 6beta-Hydroxycortisol is an endogenous probe for evaluation of drug-drug interactions involving a multispecific renal organic anion transporter, OAT3/SLC22A8, in healthy subjects. Drug Metab Dispos 42:685-694 (2014).
  50. Aida K, Hayashi H, Inamura K, Mizuno T and Sugiyama Y. Differential roles of ubiquitination in the degradation mechanism of cell surface-resident bile salt export pump and multidrug resistance-associated protein 2. Mol Pharmacol 85:482-491 (2014).
  51. 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).
  52. Yoshida S, Yamashita F, Ose A, Maeda K, Sugiyama Y and Hashida M. Automated extraction of information on chemical-P-glycoprotein interactions from the literature. J Chem Inf Model 53:2506-2510 (2013).
  53. Yoshida K, Takano J, Ishizu Y, Lezhava A, Ieiri I, Maeda K, Hayashizaki Y and Sugiyama Y. Direct and rapid genotyping of SLCO1B1 388A>G and 521T>C in human blood specimens using the SmartAmp-2 method. Aaps j 15:618-622 (2013).
  54. Yamane N, Igarashi A, Kusama M, Maeda K, Ikeda T and Sugiyama Y. Cost-effectiveness analysis of microdose clinical trials in drug development. Drug Metab Pharmacokinet 28:187-195 (2013).
  55. Yamada T, Watanabe Y, Kusama M, Sugiyama Y and Ono S. Factors associated with spontaneous reporting of adverse drug reactions in Japan. Pharmacoepidemiol Drug Saf 22:468-476 (2013).
  56. Watanabe T, Maeda K, Nakai C and Sugiyama Y. Investigation of the effect of the uneven distribution of CYP3A4 and P-glycoprotein in the intestine on the barrier function against xenobiotics: a simulation study. J Pharm Sci 102:3196-3204 (2013).
  57. Toyoshima J, Kusuhara H, Wempe MF, Endou H and Sugiyama Y. Investigation of the role of transporters on the hepatic elimination of an LAT1 selective inhibitor JPH203. J Pharm Sci 102:3228-3238 (2013).
  58. Tomaru A, Morimoto N, Morishita M, Takayama K, Fujita T, Maeda K, Kusuhara H and Sugiyama Y. Studies on the intestinal absorption characteristics of sulfasalazine, a breast cancer resistance protein (BCRP) substrate. Drug Metab Pharmacokinet 28:71-74 (2013).
  59. Takashima T, Wu C, Takashima-Hirano M, Katayama Y, Wada Y, Suzuki M, Kusuhara H, Sugiyama Y and Watanabe Y. Evaluation of breast cancer resistance protein function in hepatobiliary and renal excretion using PET with 11C-SC-62807. J Nucl Med 54:267-276 (2013).
  60. Takashima T, Shingaki T, Katayama Y, Hayashinaka E, Wada Y, Kataoka M, Ozaki D, Doi H, Suzuki M, Ishida S, Hatanaka K, Sugiyama Y, Akai S, Oku N, Yamashita S and Watanabe Y. Dynamic analysis of fluid distribution in the gastrointestinal tract in rats: positron emission tomography imaging after oral administration of nonabsorbable marker, [(18)F]Deoxyfluoropoly(ethylene glycol). Mol Pharm 10:2261-2269 (2013).
  61. Takahara N, Saga T, Inubushi M, Kusuhara H, Seki C, Ito S, Oyama N, Yokoyama O, Sugiyama Y and Fujibayashi Y. Drugs interacting with organic anion transporter-1 affect uptake of Tc-99m-mercaptoacetyl-triglycine (MAG3) in the human kidney: therapeutic drug interaction in Tc-99m-MAG3 diagnosis of renal function and possible application of Tc-99m-MAG3 for drug development. Nucl Med Biol 40:643-650 (2013).
  62. Shingaki T, Takashima T, Ijuin R, Zhang X, Onoue T, Katayama Y, Okauchi T, Hayashinaka E, Cui Y, Wada Y, Suzuki M, Maeda K, Kusuhara H, Sugiyama Y and Watanabe Y. Evaluation of Oatp and Mrp2 activities in hepatobiliary excretion using newly developed positron emission tomography tracer [11C]dehydropravastatin in rats. J Pharmacol Exp Ther 347:193-202 (2013).
  63. Nakamichi N, Shima H, Asano S, Ishimoto T, Sugiura T, Matsubara K, Kusuhara H, Sugiyama Y, Sai Y, Miyamoto K, Tsuji A and Kato Y. Involvement of carnitine/organic cation transporter OCTN1/SLC22A4 in gastrointestinal absorption of metformin. J Pharm Sci 102:3407-3417 (2013).
  64. Miyajima M, Kusuhara H, Takahashi K, Takashima T, Hosoya T, Watanabe Y and Sugiyama Y. Investigation of the effect of active efflux at the blood-brain barrier on the distribution of nonsteroidal aromatase inhibitors in the central nervous system. J Pharm Sci 102:3309-3319 (2013).
  65. Kusuhara H, Miura M, Yasui-Furukori N, Yoshida K, Akamine Y, Yokochi M, Fukizawa S, Ikejiri K, Kanamitsu K, Uno T and Sugiyama Y. Effect of coadministration of single and multiple doses of rifampicin on the pharmacokinetics of fexofenadine enantiomers in healthy subjects. Drug Metab Dispos 41:206-213 (2013).
  66. Kudo T, Hisaka A, Sugiyama Y and Ito K. Analysis of the repaglinide concentration increase produced by gemfibrozil and itraconazole based on the inhibition of the hepatic uptake transporter and metabolic enzymes. Drug Metab Dispos 41:362-371 (2013).
  67. 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).
  68. Ito S, Ando H, Ose A, Kitamura Y, Ando T, Kusuhara H and Sugiyama Y. Relationship between the urinary excretion mechanisms of drugs and their physicochemical properties. J Pharm Sci 102:3294-3301 (2013).
  69. Imamura Y, Murayama N, Okudaira N, Kurihara A, Inoue K, Yuasa H, Izumi T, Kusuhara H and Sugiyama Y. Effect of the fluoroquinolone antibacterial agent DX-619 on the apparent formation and renal clearances of 6beta-hydroxycortisol, an endogenous probe for CYP3A4 inhibition, in healthy subjects. Pharm Res 30:447-457 (2013).
  70. Imai S, Kikuchi R, Tsuruya Y, Naoi S, Nishida S, Kusuhara H and Sugiyama Y. Epigenetic regulation of organic anion transporting polypeptide 1B3 in cancer cell lines. Pharm Res 30:2880-2890 (2013).
  71. Imai S, Kikuchi R, Kusuhara H and Sugiyama Y. DNA methylation and histone modification profiles of mouse organic anion transporting polypeptides. Drug Metab Dispos 41:72-78 (2013).
  72. Ikeda T, Aoyama S, Tozuka Z, Nozawa K, Hamabe Y, Matsui T, Kainuma M, Hasegawa S, Maeda K and Sugiyama Y. Microdose pharmacogenetic study of 14C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9 *3 on its pharmacokinetics and metabolism. Eur J Pharm Sci 49:642-648 (2013).
  73. Ieiri I, Tsunemitsu S, Maeda K, Ando Y, Izumi N, Kimura M, Yamane N, Okuzono T, Morishita M, Kotani N, Kanda E, Deguchi M, Matsuguma K, Matsuki S, Hirota T, Irie S, Kusuhara H and Sugiyama Y. Mechanisms of pharmacokinetic enhancement between ritonavir and saquinavir; micro/small dosing tests using midazolam (CYP3A4), fexofenadine (p-glycoprotein), and pravastatin (OATP1B1) as probe drugs. J Clin Pharmacol 53:654-661 (2013).
  74. Hume WE, Shingaki T, Takashima T, Hashizume Y, Okauchi T, Katayama Y, Hayashinaka E, Wada Y, Kusuhara H, Sugiyama Y and Watanabe Y. The synthesis and biodistribution of [(11)C]metformin as a PET probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1) in vivo. Bioorg Med Chem 21:7584-7590 (2013).
  75. Hayashi H and Sugiyama Y. Bile salt export pump (BSEPABCB11): trafficking and sorting disturbances. Curr Mol Pharmacol 6:95-103 (2013).
  76. Godoy P, Hewitt NJ, Albrecht U, Andersen ME, Ansari N, Bhattacharya S, Bode JG, Bolleyn J, Borner C, Bottger J, Braeuning A, Budinsky RA, Burkhardt B, Cameron NR, Camussi G, Cho CS, Choi YJ, Craig Rowlands J, Dahmen U, Damm G, Dirsch O, Donato MT, Dong J, Dooley S, Drasdo D, Eakins R, Ferreira KS, Fonsato V, Fraczek J, Gebhardt R, Gibson A, Glanemann M, Goldring CE, Gomez-Lechon MJ, Groothuis GM, Gustavsson L, Guyot C, Hallifax D, Hammad S, Hayward A, Haussinger D, Hellerbrand C, Hewitt P, Hoehme S, Holzhutter HG, Houston JB, Hrach J, Ito K, Jaeschke H, Keitel V, Kelm JM, Kevin Park B, Kordes C, Kullak-Ublick GA, LeCluyse EL, Lu P, Luebke-Wheeler J, Lutz A, Maltman DJ, Matz-Soja M, McMullen P, Merfort I, Messner S, Meyer C, Mwinyi J, Naisbitt DJ, Nussler AK, Olinga P, Pampaloni F, Pi J, Pluta L, Przyborski SA, Ramachandran A, Rogiers V, Rowe C, Schelcher C, Schmich K, Schwarz M, Singh B, Stelzer EH, Stieger B, Stober R, Sugiyama Y, Tetta C, Thasler WE, Vanhaecke T, Vinken M, Weiss TS, Widera A, Woods CG, Xu JJ, Yarborough KM and Hengstler JG. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87:1315-1530 (2013).
  77. Chang CH, Kusama M, Ono S, Sugiyama Y, Orii T and Akazawa M. Assessment of statin-associated muscle toxicity in Japan: a cohort study conducted using claims database and laboratory information. BMJ Open 3:(2013).
  78. Zhao P, Vieira Mde L, Grillo JA, Song P, Wu TC, Zheng JH, Arya V, Berglund EG, Atkinson AJ, Jr., Sugiyama Y, Pang KS, Reynolds KS, Abernethy DR, Zhang L, Lesko LJ and Huang SM. Evaluation of exposure change of nonrenally eliminated drugs in patients with chronic kidney disease using physiologically based pharmacokinetic modeling and simulation. J Clin Pharmacol 52:91s-108s (2012).
  79. Yoshikado T and Sugiyama Y. [Transporters and molecular-targeted drugs]. Nihon Rinsho 70 Suppl 8:688-694 (2012).
  80. Wempe MF, Rice PJ, Lightner JW, Jutabha P, Hayashi M, Anzai N, Wakui S, Kusuhara H, Sugiyama Y and Endou H. Metabolism and pharmacokinetic studies of JPH203, an L-amino acid transporter 1 (LAT1) selective compound. Drug Metab Pharmacokinet 27:155-161 (2012).
  81. Takashima T, Kitamura S, Wada Y, Tanaka M, Shigihara Y, Ishii H, Ijuin R, Shiomi S, Nakae T, Watanabe Y, Cui Y, Doi H, Suzuki M, Maeda K, Kusuhara H, Sugiyama Y and Watanabe Y. PET imaging-based evaluation of hepatobiliary transport in humans with (15R)-11C-TIC-Me. J Nucl Med 53:741-748 (2012).
  82. Tachibana T, Kato M and Sugiyama Y. Prediction of nonlinear intestinal absorption of CYP3A4 and P-glycoprotein substrates from their in vitro Km values. Pharm Res 29:651-668 (2012).
  83. Sugiyama Y. An interview with Yuichi Sugiyama. Trends Pharmacol Sci 33:466-467 (2012).
  84. Shitara Y, Takeuchi K, Nagamatsu Y, Wada S, Sugiyama Y and Horie T. Long-lasting inhibitory effects of cyclosporin A, but not tacrolimus, on OATP1B1- and OATP1B3-mediated uptake. Drug Metab Pharmacokinet 27:368-378 (2012).
  85. Shimizu K, Takashima T, Yamane T, Sasaki M, Kageyama H, Hashizume Y, Maeda K, Sugiyama Y, Watanabe Y and Senda M. Whole-body distribution and radiation dosimetry of [11C]telmisartan as a biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3. Nucl Med Biol 39:847-853 (2012).
  86. Nakakariya M, Ono M, Amano N, Moriwaki T, Maeda K and Sugiyama Y. In vivo biliary clearance should be predicted by intrinsic biliary clearance in sandwich-cultured hepatocytes. Drug Metab Dispos 40:602-609 (2012).
  87. Misawa T, Hayashi H, Sugiyama Y and Hashimoto Y. Discovery and structural development of small molecules that enhance transport activity of bile salt export pump mutant associated with progressive familial intrahepatic cholestasis type 2. Bioorg Med Chem 20:2940-2949 (2012).
  88. Misawa T, Hayashi H, Makishima M, Sugiyama Y and Hashimoto Y. E297G mutated bile salt export pump (BSEP) function enhancers derived from GW4064: structural development study and separation from farnesoid X receptor-agonistic activity. Bioorg Med Chem Lett 22:3962-3966 (2012).
  89. Kusuhara H, Furuie H, Inano A, Sunagawa A, Yamada S, Wu C, Fukizawa S, Morimoto N, Ieiri I, Morishita M, Sumita K, Mayahara H, Fujita T, Maeda K and Sugiyama Y. Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP. Br J Pharmacol 166:1793-1803 (2012).
  90. Kotani N, Maeda K, Debori Y, Camus S, Li R, Chesne C and Sugiyama Y. Expression and Transport Function of Drug Uptake Transporters in Differentiated HepaRG Cells. Mol Pharm (2012).
  91. Kimoto E, Yoshida K, Balogh LM, Bi YA, Maeda K, El-Kattan A, Sugiyama Y and Lai Y. Characterization of Organic Anion Transporting Polypeptide (OATP) Expression and Its Functional Contribution to the Uptake of Substrates in Human Hepatocytes. Mol Pharm (2012).
  92.  Kato K, Kusuhara H, Kumagai Y, Ieiri I, Mori H, Ito S, Nakai Y, Maeda K and Sugiyama Y. Association of multidrug resistance-associated protein 2 single nucleotide polymorphism rs12762549 with the basal plasma levels of phase II metabolites of isoflavonoids in healthy Japanese individuals. Pharmacogenet Genomics 22:344-354 (2012).
  93. Kataoka M, Takashima T, Shingaki T, Hashidzume Y, Katayama Y, Wada Y, Oh H, Masaoka Y, Sakuma S, Sugiyama Y, Yamashita S and Watanabe Y. Dynamic analysis of GI absorption and hepatic distribution processes of telmisartan in rats using positron emission tomography. Pharm Res 29:2419-2431 (2012).
  94. Jin L, Kikuchi R, Saji T, Kusuhara H and Sugiyama Y. Regulation of tissue-specific expression of renal organic anion transporters by hepatocyte nuclear factor 1 alpha/beta and DNA methylation. J Pharmacol Exp Ther 340:648-655 (2012).
  95. Ito S, Kusuhara H, Yokochi M, Toyoshima J, Inoue K, Yuasa H and Sugiyama Y. Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. J Pharmacol Exp Ther 340:393-403 (2012).
  96. Ito S, Kusuhara H, Kumagai Y, Moriyama Y, Inoue K, Kondo T, Nakayama H, Horita S, Tanabe K, Yuasa H and Sugiyama Y. N-methylnicotinamide is an endogenous probe for evaluation of drug-drug interactions involving multidrug and toxin extrusions (MATE1 and MATE2-K). Clin Pharmacol Ther 92:635-641 (2012).
  97. Imawaka H, Kusama M, Ito K, Ono S and Sugiyama Y. Inclusion of human intravenous study data in new drug applications-impact of the Japanese guidance. J Pharm Sci 101:2557-2563 (2012).
  98. Ijuin R, Takashima T, Watanabe Y, Sugiyama Y and Suzuki M. Synthesis of [(11)C]dehydropravastatin, a PET probe potentially useful for studying OATP1B1 and MRP2 transporters in the liver. Bioorg Med Chem 20:3703-3709 (2012).
  99. Ieiri I, Fukae M, Maeda K, Ando Y, Kimura M, Hirota T, Nakamura T, Iwasaki K, Matsuki S, Matsuguma K, Kanda E, Deguchi M, Irie S and Sugiyama Y. Pharmacogenomic/pharmacokinetic assessment of a four-probe cocktail for CYPs and OATPs following oral microdosing. Int J Clin Pharmacol Ther 50:689-700 (2012).
  100. Ieiri I, Doi Y, Maeda K, Sasaki T, Kimura M, Hirota T, Chiyoda T, Miyagawa M, Irie S, Iwasaki K and Sugiyama Y. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose. J Clin Pharmacol 52:1078-1089 (2012).
  101. Hirai Y, Yamanaka Y, Kusama M, Ishibashi T, Sugiyama Y and Ono S. Analysis of the success rates of new drug development in Japan and the lag behind the US. Health Policy 104:241-246 (2012).
  102. Hayashi H, Naoi S, Nakagawa T, Nishikawa T, Fukuda H, Imajoh-Ohmi S, Kondo A, Kubo K, Yabuki T, Hattori A, Hirouchi M and Sugiyama Y. Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4) and mediates internalization of MRP4. J Biol Chem 287:15054-15065 (2012).
  103. Hayashi H, Mizuno T, Horikawa R, Nagasaka H, Yabuki T, Takikawa H and Sugiyama Y. 4-Phenylbutyrate modulates ubiquitination of hepatocanalicular MRP2 and reduces serum total bilirubin concentration. J Hepatol 56:1136-1144 (2012).
  104. Hayashi H, Inamura K, Aida K, Naoi S, Horikawa R, Nagasaka H, Takatani T, Fukushima T, Hattori A, Yabuki T, Horii I and Sugiyama Y. AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function. Hepatology 55:1889-1900 (2012).
  105. Endo S, Fukahori A, Tokuhiro S, Shinagawa A, Walker J, Yoshihara K, Ishizuka H, Ieiri I and Sugiyama Y. Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure. J Hum Genet 57:531-544 (2012).
  106. Chiba K, Kato M, Ito T, Suwa T and Sugiyama Y. Inter-individual variability of in vivo CYP2D6 activity in different genotypes. Drug Metab Pharmacokinet 27:405-413 (2012).


Review Articles(English, 2012~Present)

  1. Hayashi, H. and Y. Sugiyama. "Bile salt export pump (BSEP/ABCB11): trafficking and sorting disturbances." Curr Mol Pharmacol 6(2): 95-103 (2013)
  2. Godoy, P., N. J. Hewitt, U. Albrecht, M. E. Andersen, N. Ansari, S. Bhattacharya, J. G. Bode, J. Bolleyn, C. Borner, J. Bottger, A. Braeuning, R. A. Budinsky, B. Burkhardt, N. R. Cameron, G. Camussi, C. S. Cho, Y. J. Choi, J. Craig Rowlands, U. Dahmen, G. Damm, O. Dirsch, M. T. Donato, J. Dong, S. Dooley, D. Drasdo, R. Eakins, K. S. Ferreira, V. Fonsato, J. Fraczek, R. Gebhardt, A. Gibson, M. Glanemann, C. E. Goldring, M. J. Gomez-Lechon, G. M. Groothuis, L. Gustavsson, C. Guyot, D. Hallifax, S. Hammad, A. Hayward, D. Haussinger, C. Hellerbrand, P. Hewitt, S. Hoehme, H. G. Holzhutter, J. B. Houston, J. Hrach, K. Ito, H. Jaeschke, V. Keitel, J. M. Kelm, B. Kevin Park, C. Kordes, G. A. Kullak-Ublick, E. L. LeCluyse, P. Lu, J. Luebke-Wheeler, A. Lutz, D. J. Maltman, M. Matz-Soja, P. McMullen, I. Merfort, S. Messner, C. Meyer, J. Mwinyi, D. J. Naisbitt, A. K. Nussler, P. Olinga, F. Pampaloni, J. Pi, L. Pluta, S. A. Przyborski, A. Ramachandran, V. Rogiers, C. Rowe, C. Schelcher, K. Schmich, M. Schwarz, B. Singh, E. H. Stelzer, B. Stieger, R. Stober, Y. Sugiyama, C. Tetta, W. E. Thasler, T. Vanhaecke, M. Vinken, T. S. Weiss, A. Widera, C. G. Woods, J. J. Xu, K. M. Yarborough and J. G. Hengstler. "Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME." Arch Toxicol 87(8): 1315-1530 (2013)
  3. 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).
  4. Tomita Y, Maeda K, Sugiyama Y. Ethnic Variability in the Plasma Exposures of OATP1B1 Substrates Such as HMG-CoA Reductase Inhibitors: A Kinetic Consideration of Its Mechanism. Clin Pharmacol Ther 94:37-51 (2013).
  5. Shitara Y, Maeda K, Ikejiri K, Yoshida K, Horie T and Sugiyama Y. Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption. Biopharm Drug Dispos 34:45-78 (2013).
  6. Maeda K and Sugiyama Y. Transporter biology in drug approval: regulatory aspects. Mol Aspects Med 34:711-718 (2013).
  7. Giacomini KM, Balimane PV, Cho SK, Eadon M, Edeki T, Hillgren KM, Huang SM, Sugiyama Y, Weitz D, Wen Y, Xia CQ, Yee SW, Zimdahl H and Niemi M. International Transporter Consortium commentary on clinically important transporter polymorphisms. Clin Pharmacol Ther 94:23-26 (2013).
  8. Chu X, Korzekwa K, Elsby R, Fenner K, Galetin A, Lai Y, Matsson P, Moss A, Nagar S, Rosania GR, Bai JP, Polli JW, Sugiyama Y and Brouwer KL. Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver. Clin Pharmacol Ther 94:126-141 (2013).

Book Chapters and Proceedings (English, 2012~)

  1. Giacomini KM and Sugiyama Y. Membrane transporters and drug response, Chapter 5, in Goodman & Gilmans The Pharmacological Basis of Therapeutics , 13th Edition (Brunton LL, Chabner BA, Knollman B  eds)  McGraw-Hill Companies, New York, in press (2017)
  2. Maeda, K., and Sugiyama, Y. 13. Excretion systems In: "Encyclopedia of Drug Metabolism and Interactions" ed. by Lyubimov A.V., John Wiley & Sons, Inc., New York, pp. 1-32 (2012)
  3. Kusuhara H, Maeda K and Sugiyama Y “Impact of Drug Transporters in the Pharmacological and Adverse Reactions of Drugs” pp563-598 (2012) In New Horizons in Predictive Toxicology: Current Status and Application, Ed. by Wilson AGE, in press