Welcome to MSS Web Site









The Division of Medicinal Safety Science (MSS) was established on April 1, 2002 and is engaged in the basic research of medicinal products. The major activities are focused on medical safety control and experimental studies to determine the appropriate usage of medicine. The former activity is a comprehensive strategy of safety control action against adverse events of post-marketing medicines, especially to avoid serious adverse effects. The latter research addresses the mechanism(s) of adverse events in susceptible individuals, using pharmacoepidemiological approaches including population pharmacokinetics, pharmacogenomics, etc.

The major research objectives of the MSS are addressed by the following four sections:

 

First Section
The development of a comprehensive methodology for the collection, analysis and evaluation of drug safety information, and the study of medicinal safety control action.

Second Section
The identification of potential genetic markers that may predispose an individual to a drug-induced adverse event from approved medicinal products.

 

Third Section
The elucidation of factors that may affect the pharmacokinetics of drugs in patients predisposed to the manifestation of drug-induced adverse effects using population pharmacokinetic procedures.

 

Fourth Section

Mainly, we are conducting research on adverse effects of medicines using computer such as fragment molecular orbital method and maintain the NIHS network.

 

 




Publications

2011

  1. Sato Y, Yamamoto N, Kunitoh H, Ohe Y, Minami H, Laird NM, Katori N, Saito Y, Ohnami S, Sakamoto H, Sawada JI, Saijo N, Yoshida T, Tamura T.: Genome-Wide Association Study on Overall Survival of Advanced Non-small Cell Lung Cancer Patients Treated with Carboplatin and Paclitaxel., J Thorac Oncol., in press.
  2. Saito Y, Yamamoto N, Katori N, Maekawa K, Fukushima-Uesaka H, Sugimoto D, Kurose K, Sai K, Kaniwa N, Sawada JI, Kunitoh H, Ohe Y, Yoshida T, Matsumura Y, Saijo N, Okuda H, Tamura T.: Genetic polymorphisms and haplotypes of POR encoding cytochrome P450 oxidoreductase in a Japanese population. Drug Metab. Pharmacokinet., in press.
  3. aeki M, Kurose K, Hasegawa R, Tohkin M.: Functional analysis of genetic variations in the 5'-flanking region of the human MDR1 gene. Mol. Genet. Metab., in press.
  4. Hanioka N, Matsumoto K,Saito Y and Narimatsu S: Influence of CYP2C8*13 and CYP2C8*14 Alleles on Amiodarone N-Deethylation. Basic Clin. Pharmacol. Toxicol., in press.

2010

  1. Sai K, Saito Y, Maekawa K, Kim SR, Kaniwa N, Nishimaki-Mogami T, Sawada J, Shirao K, Hamaguchi T, Yamamoto N, Kunitoh H, Ohe Y, Yamada Y, Tamura T, Yoshida T, Matsumura Y, Ohtsu A, Saijo N, Minami H.: Additive effects of drug transporter genetic polymorphisms on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients. Cancer Chemother Pharmacol. 66: 95-105 (2010).
  2. Matsubara J, Ono M, Honda K, Negishi A, Ueno H, Okusaka T, Furuse J, Furuta K, Sugiyama E, Saito Y, Kaniwa N, Sawada J, Shoji A, Sakuma T, Chiba T, Saijo N, Hirohashi S, Yamada T.: Survival prediction for pancreatic cancer patients receiving gemcitabine treatment. Mol Cell Proteomics. 9: 695-704 (2010).
  3. Ikeda H., Takahashi Y., Yamazaki E., Fujiwara T., Kaniwa N., Saito Y., Aihara M., Kashiwagi M. and Muramatsu M.: HLA-class ? markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia, 51: 297-300 (2010).
  4. Sugiyama E., Kaniwa N., Kim S.R., Hasegawa R.,Saito Y., Ueno H.COkusaka T., Ikeda M., Morizane C., Kondo S., Yamamoto N., Tamura T., Furuse J., Ishii H., Yoshida T., Saijo N. and Sawada J.: Population pharmacokinetics of gemcitabine and its metabolite in Japanese cancer patients: Impact of genetic polymorphisms. Clin. Pharmacokinet., 49: 549-558 (2010).
  5. anioka N., Matsumoto K.,Saito Y. and Narimatsu S.: Functional characterization of CYP2C8.13 and CYP2C8.14: catalytic activities toward paclitaxel.  Basic Clin. Pharmacol. Toxicol., 107: 565-569 (2010).
  6. Sai K.,Saito Y., Tatewaki N., Hosokawa M., Kaniwa N., Nishimaki-Mogami T., Naito M., Sawada J., Shirao K., Hamaguchi T., Yamamoto N., Kunitoh H., Tamura T., Yamada Y., Ohe Y., Yoshida T., Minami H., Ohtsu A., Matsumura Y., Saijo N., Okuda H.: Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in Japanese cancer patients. Br. J. Clin. Pharmacol., 70: 222-233 (2010).
  7. aekawa K., Harakawa N., Yoshimura T., Kim S.R., Fujimura Y., Aohara F., Sai K., Katori N., Tohkin M., Naito M., Hasegawa R., Okuda H., Sawada J., Niwa T. and Saito Y.: CYP3A4*16 and CYP3A4*18 Alleles Found in East Asians Exhibit Differential Catalytic Activities for Seven CYP3A4 Substrate Drugs. Drug metab. Dispos., 38: 2100-2104 (2010).
  8. Tohkin M, Ishiguro A, Kaniwa N, Saito Y, Kurose K, Hasegawa R.: Prediction of severe adverse drug reactions using pharmacogenetic biomarkers. Drug Metab. Pharmacokinet., 25: 122-133 (2010).
  9. Ishii-Watabe A, Saito Y, Suzuki T, Tada M, Ukaji M, Maekawa K, Kurose K, Kaniwa N, Sawada JI, Kawasaki N, Yamaguchi T, Eguchi Nakajima T, Kato K, Yamada Y, Shimada Y, Yoshida T, Ura T, Saito M, Muro K, Doi T, Fuse N, Yoshino T, Ohtsu A, Saijo N, Hamaguchi T, Okuda H, Matsumura Y.: Genetic polymorphisms of FCGRT encoding FcRn in a Japanese population and their functional analysis. Drug Metab. Pharmacokinet., 25: in press (2010).
  10. K. Yamagishi, K. Yamamoto, Y. Mochizuki, T. Nakano, S. Yamada, H. Tokiwa, "Flexible ligand recognition of peroxisome proliferator-activated receptor-g (PPARg)", Bioorg. Med. Chem. Lett. 20, 3344 (2010).
  11. Y. Okiyama, T. Nakano, K. Yamashita, Y. Mochizuki, N. Taguchi, S. Tanaka, "Acceleration of fragment molecular orbital calculations with Cholesky decomposition approach", Chem. Phys. Lett. 490, 84-89 (2010).
  12. Y. Mochizuki, K. Yamashita, K. Fukuzawa, K. Takematsu, H. Watanabe, N. Taguchi, Y. Okiyama, M. Tsuboi, T. Nakano, S. Tanaka, "Large-scale FMO-MP3 calculations on the surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA)", Chem. Phys. Lett. 493, 346-352 (2010).
  13. H. Watanabe, Y. Okiyama, T. Nakano, S. Tanaka, gIncorporation of solvation effects into the fragment molecular orbital calculations with the PoissonBoltzmann equationh, Chem. Phys. Lett. 500, 116-119 (2010).
  14. I. Kurisaki, K. Fukuzawa, T. Nakano, Y. Mochizuki, H. Watanabe, S. Tanaka, gFragment molecular orbital (FMO) study on stabilization mechanism of neuro-oncological ventral antigen (NOVA)RNA complex systemh, J. Mol. Struct. (THEOCHEM) 962, 45-55 (2010).
  15. M. Sato, H. Yamataka, Y. Komeiji, Y. Mochizuki, T. Nakano, gDoes Amination of Formaldehyde Proceed Through a Zwitterionic Intermediate in Water? Fragment Molecular Orbital Molecular Dynamics Simulations by Using Constraint Dynamicsh, Chemistry A European Journal, 16, 6430-6433 (2010).
  16. T. Ogawa, T. Nakano, gThe Extended Universal Force Field (XUFF): Theory and Applicationsh, Chem-Bio. Info. J. 10, 111-133 (2010).

2009

  1. Ueno H, Kaniwa N, Okusaka T, Ikeda M, Morizane C, Kondo S, Sugiyama E, Kim SR, Hasegawa R, Saito Y, Yoshida T, Saijo N, Sawada J.: Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients. Br J Cancer, 100: 870-873 (2009).
  2. Matsubara J, Ono M, Negishi A, Ueno H, Okusaka T, Furuse J, Furuta K, Sugiyama E, Saito Y, Kaniwa N, Sawada J, Honda K, Sakuma T, Chiba T, Saijo N, Hirohashi S, Yamada T.: Identification of a predictive biomarker for hematologic toxicities of gemcitabine. J Clin Oncol, 27: 2261-2268 (2009).
  3. Maekawa K, Yoshimura T, Saito Y, Fujimura Y, Aohara F, Emoto C, Iwasaki K, Hanioka N, Narimatsu S, Niwa T, Sawada J.: Functional characterization of CYP3A4.16: catalytic activities toward midazolam and carbamazepine. Xenobiotica, 39: 140-147 (2009).
  4. Tatewaki N, Maekawa K, Katori N, Kurose K, Kaniwa N, Yamamoto N, Kunitoh H, Ohe Y, Nokihara H, Sekine I, Tamura T, Yoshida T, Saijo N, Saito Y, Sawada J.: Genetic variations and haplotype structures of the glutathione S-transferase genes, GSTT1 and GSTM1, in a Japanese patient population. Drug Metab Pharmacokinet., 24: 118-126 (2009).
  5. Sato Y, Laird NM, Nagashima K, Kato R, Hamano T, Yafune A, Kaniwa N, Saito Y, Sugiyama E, Kim SR, Furuse J, Ishii H, Ueno H, Okusaka T, Saijo N, Sawada JI, Yoshida T.: A new statistical screening approach for finding pharmacokinetics-related genes in genome-wide studies. Pharmacogenomics J. 9: 137-146 (2009)
  6. Saito Y, Sai K, Maekawa K, Kaniwa N, Shirao K, Hamaguchi T, Yamamoto N, Kunitoh H, Ohe Y, Yamada Y, Tamura T, Yoshida T, Minami H, Ohtsu A, Matsumura Y, Saijo N, Sawada J.: Close association of UGT1A9 IVS1+399C>T with UGT1A1*28, *6, or *60 haplotype and its apparent influence on 7-ethyl-10-hydroxycamptothecin (SN-38) glucuronidation in Japanese. Drug Metab Dispos., 37: 272-276 (2009).
  7. Sai K., Minami H., Saito Y. and Sawada J.: Impact of UDP-glucuronosyltransferase 1A haplotypes on irinotecan treatment.  Pharmacogenomics, Anticancer Drug Discovery, and Response (ed. F. Innocenti), Human Press, Totawa NJ, 2009, pp. 267-286.
  8. Sugiyama E, Lee SJ, Lee SS, Kim WY, Kim SR, Tohkin M, Hasegawa R, Okuda H, Kawamoto M, Kamatani N, Sawada J, Kaniwa N, Saito Y, Shin JG.: Ethnic differences of two non-synonymous single nucleotide polymorphisms in CDA gene. Drug Metab Pharmacokinet. 24: 553-556 (2009).
  9. Fukushima-Uesaka H, Saito Y, Maekawa K, Kurose K, Sugiyama E, Katori N, Kaniwa N, Hasegawa R, Hamaguchi T, Eguchi-Nakajima T, Kato K, Yamada Y, Shimada Y, Yoshida T, Yamamoto N, Nokihara H, Kunitoh H, Ohe Y, Tamura T, Ura T, Saito M, Muro K, Doi T, Fuse N, Yoshino T, Ohtsu A, Saijo N, Matsumura Y, Okuda H, Sawada J.: Genetic polymorphisms of copper- and platinum drug-efflux transporters ATP7A and ATP7B in Japanese cancer patients. Drug Metab Pharmacokinet. 24: 565-574 (2009).
  10. Y. Komeiji, T. Ishikawa, Y. Mochizuki, H. Yamataka, T. Nakano, gFragment Molecular Orbital method-based Molecular Dynamics (FMO-MD) as a simulator for chemical reactions in explicit solvationh, J. Comput. Chem. 30, 40-50 (2009).
  11. Y. Komeiji, Y. Mochizuki, T. Nakano, and D. G. Fedorov, gFragment Molecular Orbital-based Molecular Dynamics (FMO-MD), a quantum simulation tool for large molecular systemsh, J. Mol. Struct. (Theochem), 898, 2-7 (2009).
  12. T. Fujita, K. Fukuzawa, Y. Mochizuki, T. Nakano, S. Tanaka, "Accuracy of fragmentation in ab initio calculations of hydrated sodium cation", Chem. Phys. Lett. 478 295-300 (2009).
  13. T. Watanabe, Y. Inadomi, H. Umeda, K. Fukuzawa, S. Tanaka, T. Nakano, U. Nagashima, "Fragment Molecular Orbital (FMO) and FMO-MO Calculations of DNA: Accuracy Validation of Energy and Interfragment Interaction Energy", J. Comp. Theor. Nanosci. 6, 1328-1337 (2009).
  14. K. Takematsu, K. Fukuzawa, K. Omagari, S. Nakajima, K. Nakajima, Y. Mochizuki, T. Nakano, H. Watanabe, S. Tanaka, "Possibility of mutation prediction of influenza hemagglutinin by combination of hemadsorption experiment and quantum chemical calculation for antibody binding", J. Phys. Chem. B 113, 4991-4994 (2009).
  15. N. Taguchi, Y. Mochizuki, T. Nakano, S. Amari, K. Fukuzawa, T. Ishikawa, M. Sakurai, S. Tanaka, "Fragment Molecular Orbital Calculations on Red Fluorescent Proteins (DsRed and mFruits)", J. Phys. Chem. B 113, 1153-1161 (2009).
  16. Y. Okiyama, H. Watanabe, K. Fukuzawa, T. Nakano, Y. Mochizuki, T. Ishikawa, K. Ebina, S. Tanaka, "Application of the fragment molecular orbital method for determination of atomic charges on polypeptides. II. Towards an improvement of force fields used for classical molecular dynamics simulations", Chem. Phys. Lett. 467, 417-423 (2009).

2008

  1. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, Sawada J, Furuya H, Takahashi Y, Muramatsu M, Kinoshita S, Abe M, Ikeda H, Kashiwagi M, Song Y, Ueta M, Sotozono C, Ikezawa Z, Hasegawa R; JSAR research group.: HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics, 9: 1617-1622 (2008).
  2. Kim SR, Saito Y, Maekawa K, Sugiyama E, Kaniwa N, Ueno H, Okusaka T, Ikeda M, Morizane C, Yamamoto N, Yoshida T, Kamatani N, Furuse J, Ishii H, Saijo N, Ozawa S, Sawada J.: Twenty novel genetic variations and haplotype structures of the DCK gene encoding human deoxycytidine kinase (dCK). Drug Metab Pharmacokinet., 23:379-384 (2008).
  3. Sai K., Saito Y., Itoda M., Fukushima-Uesaka H., Ozawa S., Kurose K., Kaniwa N.,  Kawamoto M., Kamatani N., Shirao K., Yamamoto N., Hamaguchi T., Kunitoh H., Ohe Y., Yamada Y., Tamura T., Yoshida T., Minami H., Matsumura Y., Ohtsu A., Saijo  N., J. Sawada: Genetic variations and haplotypes of ABCC2 encoding MRP2 in a Japanese population. Drug. Metab. Pharmacokinet., 23: 139-147 (2008).
  4. Sai K., Saito Y., Fukushima-Uesaka H., Kurose K., Kaniwa N., Kamatani N., Shirao K., Yamamoto N., Hamaguchi T., Kunitoh H., Ohe Y., Tamura T., Yamada Y., Minami H., Ohtsu A., Yoshida T., Saijo N., Sawada J.: Impact of CYP3A4 haplotypes on irinotecan pharmacokinetics in Japanese cancer patients. Cancer Chemother. Pharmacol., 62: 529-537 (2008).
  5. Saeki M, Kurose K, Tohkin M, Hasegawa R.: Identification of the functional vitamin D response elements in the human MDR1 gene. Biochem. Pharmacol., 76: 531-542 (2008). 
  6. Kurose K, Saeki M, Tohkin M, Hasegawa R.: Thyroid hormone receptor mediates human MDR1 gene expression-Identification of the response region essential for gene expression. Arch Biochem Biophys., 474: 82-90 (2008).
  7. M. Ito, K. Fukuzawa, Y. Mochizuki, T. Nakano, S. Tanaka, gAb Initio Fragment Molecular Orbital Study of Molecular Interactions between Liganded Retinoid X Receptor and Its Coactivator; Part II: Influence of Mutations in Transcriptional Activation Function 2 Activating Domain Core on the Molecular Interactionsh, J. Phys. Chem. A 112, 1986-1998 (2008).
  8. M. Sato, H. Yamataka, Y. Komeiji, Y. Mochizuki, T. Ishikawa, T. Nakano, gHow Does an SN2 Reaction Take Place in Solution? Full Ab Initio MD Simulations for the Hydrolysis of the Methyl Diazonium Ionh, J. Am. Chem. Soc. 130, 2396-2397 (2008).
  9. K. Koyano and T. Nakano, gInteraction of HIV-1 aspartic protease with its inhibitor, by molecular dynamics and ab initio fragment molecular orbital methodh, J. Synchrotron Rad. 15, 239242 (2008).
  10. Y. Mochizuki, K. Yamashita, T. Murase, T. Nakano, K. Fukuzawa, K. Takematsu, H. Watanabe, S. Tanaka, gLarge scale FMO-MP2 calculations on a massively parallel-vector computerh, Chem. Phys. Lett. 457,  396-403 (2008).
  11. T. Harada, K. Yamagishi, T. Nakano, K. Kitaura, H. Tokiwa, "Ab initio fragment molecular orbital study of ligand binding to human progesterone receptor ligand-binding domain", Naunyn-Schmiedeberg's Arch. Pharmac. 377, 607-615 (2008).
  12. M. Ito, K. Fukuzawa, T. Ishikawa, Y. Mochizuki, T. Nakano, and S. Tanaka, gAb Initio Fragment Molecular Orbital Study of Molecular Interactions in Liganded Retinoid X Receptor: Specification of Residues Associated with Ligand Inducible Information Transmissionh, J. Phys. Chem. B, 112, 12081-12094 (2008).
  13. T. Ishikawa, Y. Mochizuki, S. Amari, T. Nakano, S. Tanaka, K. Tanaka, gAn application of fragment interaction analysis based on local MP2h, Chem. Phys. Lett. 463, 189-194 (2008).

2007

1.      Saeki M, Saito Y, Sai K, Maekawa K, Kaniwa N, Sawada J, Kawamoto M, Saito A, Kamatani N (2007) A combinatorial haplotype of the UDP-glucuronosyltransferase 1A1 gene (#60-#IB) increases total bilirubin concentrations in Japanese volunteers. Clin Chem. 2007, 53, 356-358.

2.      Hasegawa R, Hirata-Koizumi M, Dourson M, Parker A, Hirose A, Nakai S, Kamata E, Ema M (2007) Pediatric susceptibility to 18 industrial chemicals: A comparative analysis of newborn with young animals. Regul Toxicol Pharmacol, 47, 296-307.

3.      Sugiyama E, Kaniwa N, Kim SR, Kikura-Hanajiri R, Hasegawa R, Maekawa K, Saito Y, Ozawa S, Sawada J, Kamatani N, Furuse J, Ishii H, Yoshida T, Ueno H, Okusaka T, Saijo N (2007) Pharcokinetics of gemcitabine in Japanese cancer patients: the impact of a cytidine deaminase polymorphism. J Clin Oncol, 25, 32-42.

4.      Fukushima-Uesaka H, Saito Y, Tohkin M, Maekawa K, Hasegawa R, Kawamoto M, Kamatani N, Suzuki K, Yanagawa T, Kajio H, Kuzuya N, Yasuda K, Sawada J (2007) Genetic Variations and Haplotype Structures of the ABC Transporter Gene ABCC1 in a Japanese Population. Drug Metab Pharmacokinet, 22, 48-60.

5.      Hirata-Koizumi M, Saito M, Miyake S, Hasegawa R (2007) Adverse events caused by drug interactions involving glucuronoconjugates of zidovudine, valproic acid and lamotrigine, and analysis of how such potential events are discussed in package inserts of Japan, UK and USA. J Clin Pharm Ther, 32, 177-185.

6.      Hasegawa R, Saito M (2007) Domestic aspect of drugs withdrawn from foreign market. Nihon Yakurigaku Zasshi, 129, 227. Japanese

7.      Saito M, Hirata M, Urano T, Miyake S, Hasegawa (2007) Comparative analysis of clinical and non-clinical pharmacokinetic interaction of statins with other drugs. Jpn J Pharm Health Care Sci, 33, 291-300. Japanese

8.      Choi DH, Katakura Y, Matsuda R, Hayashi Y, Hirobe M, Goda Y, Ninomiya K, Shioya S (2007) Validation of a method for predicting the precision, limit of detection and range of quantitation in competitive ELISA, Anal Sci, 23, 215-218.

9.      Tanaka H, Hayashi Y, Yajima T (2007) How can we use the information of pharmacies? 1. Feature, expression and interpretation of pharmacy information. J Recipe, 6, 73-76. Japanese

10.  Iwaki K, Takeuchi N, Hayashi Y, Yajima T (2007) Vigilance of people's health. 2. Route and speed of influenza infection in and around Tokyo . J Pract Pharm, 58, 113-116. Japanese

11.  Hayashi Y, Takeuchi N, Iwaki K, Yajima T (2007) Vigilance of people's health. 3. Would you challenge correlation coefficient and cross-correlation function? J Pract Pharm, 58, 493-498. Japanese

12.  Mochizuki Y, Tanaka K, Yamashita K, Ishikawa T, Nakano T, Amari S, Segawa K, Murase T, Tokiwa H, Sakurai M (2007) Parallelized integral-direct CIS(D) calculations with multilayer fragment molecular orbital scheme, Theor Chem Acc, 117, 541-553.

13.  Mochizuki Y, Nakano T, Amari S, Ishikawa T, Tanaka K, Sakurai M, Tanaka S (2007) Fragment molecular orbital calculations on red fluorescent protein (DsRed), Chem Phys Lett, 433, 360-367.

14.  Mochizuki Y, Komeiji Y, Ishikawa T, Nakano T, Yamataka H (2007) A fully quantum mechanical simulation study on the lowest n?p* state of hydrated formaldehyde, Chem Phys Lett, 437, 66-72.

15.  Ito M, Fukuzawa K, Mochizuki Y, Nakano T, Tanaka S (2007) Ab Initio Fragment Molecular Orbital Study of Molecular Interactions between Liganded Retinoid X Receptor and Its Coactivator: Roles of Helix 12 in the Coactivator Binding Mechanism, J Phys Chem B, 111, 3525-3533.

16.  Maeda K, Schug A, Watanabe H, Fukuzawa K, Mochizuki Y, Nakano T, Tanaka S (2007) Effects of point mutations on the binding energies of estrogen receptor with estradiol, J Comput Chem Jpn, 6, 33-46. Japanese

2006

1. Ueno H, Kaniwa N (2006) Pharmacogenomics gemcitabine ? Genetic polymorphisms of citidine deaminase. Gann Bunnshi Hyouteki Chiryou, 4, 47-51. Japanese

2. Kurose K, Ikeda S, Koyano S, Tohkin M, Hasegawa R, Sawada J (2006) Identification of regulatory sites in the human PXR (NR1I2) promoter region. Mol Cell Biochem, 281, 35-43.

3. Hamamura M, Hirose A, Kamata E, Katoku K, Kuwasaki E, Oshikawa T, Nakahara Y, Ema M, Hasegawa R (2006) Semi-quantitative immunohistochemical analysis of male rat-specific a2u-globulin accumulation for chemical toxicity evaluation. J Toxicol Sci, 31, 35-47.

4. Takahashi M, Hirata-Koizumi M, Nishimura N, Ito Y, Sunaga M, Fujii S, Kamata E, Hasegawa R, Ema M (2006) Susceptibility of newborn rats to 3-ethylphenol and 4-ethylphenol compared with that of young rats. Congenit Anom, 46, 26-33.

5. Saeki M, Saito Y, Jinno H, Sai K, Ozawa S, Kurose K, Kaniwa N, Komamura K, Kotake T, Morishita H, Kamakura S, Kitakaze M, Tomoike H, Shirao K, Tamura T, Yamamoto N, Kunitoh H, Hamaguchi T, Yoshida T, Kubota K, Ohtsu A, Muto M, Minami H, Saijo N, Kamatani N, Sawada J (2006) Haplotype structures of the UGT1A gene complex in a Japanese population. Pharmacogenomics J, 6, 63-75.

6. Suzuki K, Yanagawa T, Shibasaki T, Kaniwa N, Hasegawa R, Tohkin M (2006) Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepiride in subjects with type 2 diabetes. Diabetes Res Clin Pract, 72, 148-154.

7. Maekawa K, Itoda M, Sai K, Saito Y, Kaniwa N, Shirao K, Hamaguchi T, Kunitoh H, Yamamoto N, Tamura T, Minami H, Kubota K, Ohtsu A, Yoshida T, Saijo N, Kamatani N, Ozawa S, Sawada J (2006) Genetic variation and haplotype structure of the ABC transporter gene ABCG2 in a Japanese population. Drug Metab Pharmacokinet, 21, 109-121.

8. Maekawa K, Fukushima-Uesaka H, Tohkin M, Hasegawa R, Kajio H, Kuzuya N, Yasuda K, Kawamoto M, Kamatani N, Suzuki K, Yanagawa T , Saito Y, Sawada J (2006) Four novel defective alleles and comprehensive haplotype analysis of CYP2C9 in Japanese. Pharmacogenet Genomics, 16, 497-514

9. Kim SR, Saito Y, Maekawa K, Sugiyama E, Kaniwa N, Ueno H, Okusaka T, Morizane C, Yamamoto N, Ikeda M, Yoshida T, Minami H, Furuse J, Ishii H, Saijo N, Kamatani N, Ozawa S, Sawada J (2006) Thirty novel genetic variations in the SLC29A1 gene encoding human equilibrative nucleoside transporter 1 (hENT1). Drug Metab Pharmacokinet, 21, 248-256.

10. Matsumoto M, Takahashi M, Hirata M, Hirose A, Kamata E, Hasegawa R, Ema M (2006) OECD High Production Volume Chemicals Programme: Summary of 1st to 18th SIDS Initial Assessment Meetings, ChemoBio Integrated Management, 2, 104-134. Japanese

11. Hasegawa R (2006) Pharmacokinetic interaction involved in drug adverse events. PharmStage, 6(6), 43-48. Japanese

12. Nakajima Y, Yoshitani T, Fukushima-Uesaka H, Saito Y, Kaniwa N, Kurose K, Ozawa S, Aoyagi N, Kamatani N, Yamamoto N, Kunitoh H, Ohe Y, Tamura T, Yoshida T, Minami H, Saijo N, Katori N, Sawada J (2006) Impact of the haplotype CYP3A4*16B harboring the Thr185Ser substitution on paclitaxel metabolism in Japanese patients with cancer. Clin Pharmacol Ther, 80, 179-191.

13. Sai K, Itoda M, Saito Y, Kurose K, Katori N, Kaniwa N, Komamura K, Kotake T, Morishita H, Tomoike H, Kamakura S, Kitakaze M, Tamura T, Yamamoto N, Kunitoh H, Yamada Y, Ohe Y, Shimada Y, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Kamatani N, Ozawa S, Sawada J (2006) Genetic variations and haplotype structures of the ABCB1 gene in a Japanese population: an expanded haplotype block covering the distal promoter region, and associated ethnic differences. Ann Hum Genet, 70(Pt 5), 605-622.

14. Kim SR, Ozawa S, Saito Y, Kurose K, Kaniwa N, Kamatani N, Hamaguchi T, Shirao K, Muto M, Ohtsu A, Yoshida T, Matsumura Y, Saijo N, Sawada J (2006) Fourteen novel genetic variations and haplotype structures of the TYMS gene encoding human thymidylate synthase (TS). Drug Metab Pharmacokinet, 21, 509-516

15. Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R (2006) Investigation on new molecular entities of drugs approved during 2005 in three regions, Japan, US and EU, and common and preceding approvals in current 4 years. Bull Natl Inst Health Sci, 124, 80-82. Japanese

16. Hirata-Koizumi M, Saito M, Miyake S, Hasegawa R (2006) Study on environmental risk assessment of drugs: excreted forms to environment. Bull Natl Inst Health Sci, 124, 83-86. Japanese

17. Tohkin M (2006) Bile acids regulate the physiological functions through farnesoid X receptor. Rinsho Kagaku, 35, 136-143. Japanese

2005

1. Saito M, Hirata-Koizumi M, Urano T, Miyake S, Hasegawa R (2005) A literature search on pharmacokinetic drug interactions of statins and analysis of how this is reflected in package inserts of Japan. J Clin Pharm Ther, 30, 21-37.

2. Takahashi M, Hirata M, Matsumoto M, Hirose A, Kamata E, Hasegawa R, Ema M (2005) Progress of OECD Chemical Program (No. 6) The 14th Initial Assessment Meeting of OECD High Production Volume Chemicals (Paris, 2002), ChemoBio Integrated Management, 1, 46-55. (Japanese)

3. Kaniwa N, Kurose K, Jinno H, Tanaka-Kagawa T, Saito Y, Saeki M, Sawada J, Tohkin M, Hasegawa R (2005) Racial variability in haplotype frequencies of UGT1A1 and glucuronidation activity of a novel single nucleotide polymorphism 686C>T (P229L) found in an Africa-American. Drug Metab Dispos, 33, 458-465.

4. Hirata-Koizumi M, Kusuoka O, Nishimura N, Wada H, Ogata H, Fukuda N, Ito Y, Kamata E, Ema M, Hasegawa R (2005) Susceptibility of newborn rats to hepatotoxicity of 1,3-dibromopropane and 1,1,2,2-tetrabromomethane, compared with young rats. J Toxicol Sci, 30, 29-42.

5. Nakajima Y, Saito Y, Shiseki K, Fukushima-Uesaka H, Hasegawa R, Ozawa S, Sugai K, Katoh M, Saitoh O, Ohnuma T, Kawai M, Ohtsuki T, Suzuki C, Minami N, Kimura H, Goto Y, Kamatani N, Kaniwa N, Sawada J (2005) Haplotype structures of EPHX1 and their effects on the metabolism of carbamazepine-10,11-epoxide in Japanese epileptic patients. Eur J Clin Pharmacol, 60, 25-34.

6. Kurose K, Tohkin M, Hasegawa R (2005) Transcription factor NF2d9 (LBP-1a) interacts with the positive regulatory element for the xenobiotic responsive element. Biochim Biophys Acta, 1727, 141-144.

7. Saeki M, Saito Y, Jinno H, Sai K, Kaniwa N, S. Ozawa S, Kawamoto M, Kotake T, Morishita H, Kamakura S, Kitakaze M, Tomoike H, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Kamatani N, Sawada J (2005) Genetic polymorphisms of UGT1A6 in a Japanese population. Drug Metab Pharmacokinet, 20, 85-90.

8. Koyano S, Saito Y, Sai K, Kurose K, Ozawa S, Nakajima T, Matsumoto K, Saito H, Shirao K, Yoshida T, Minami H, Ohtsu A, Saijo N, Sawada J (2005) Novel genetic polymorphisms in the NR3C1 (glucocorticoid receptor) gene in a Japanese population. Drug Metab Pharmacokinet, 20, 79-84.

9. Yonemori K, Ueno H, Okusaka T, Yamamoto N, Ikeda M, Saijo N, Yoshida T, Ishii H, Furuse J, Sugiyama E, Kim SR, Kikura-Hanajiri R, Hasegawa R, Saito Y, Ozawa S, Kaniwa N, Sawada J (2005) Severe drug toxicity associated with a single-nucleotide polymorphism of the cytidine deaminase gene in a Japanese cancer patient treated with gemcitabine plus cisplatin. Clin Cancer Res, 11, 2620-2624.

10. Kurose K, Koyano S, Ikeda S, Tohkin M, Hasegawa R, Sawada J (2005) 5f diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site. Mol Cell Biochem, 273, 79-85.

2004

1. Koyano S, Kurose K, Saito Y, Ozawa S, Hasegawa R, Komamura K, Ueno K, Kamakura S, Kitakaze M, Nakajima T, Matsumoto K, Akasawa A, Saito H, Sawada J (2004) Functional characterization of four naturally occurring variants of human pregnane X receptor (PXR): one variant causes dramatic loss of both DNA binding activity and the transactivation of the CYP3A4 promoter/enhancer region. Drug Metab Dispos, 32, 149-154.

2. Fukushima-Uesaka H, Saito Y, Watanabe H, Shiseki K, Saeki M, Nakamura T Kurose, K, Sai K, Komamura K, Ueno K, Kamakura S, Kitakaze M, Hanai S, Nakajima T, Matsumoto K, Saito H, Goto Y, Kimura H, Katoh M, Sugai K, Minami N, Shirao K, Tamura T, Yamamoto N, Minami H, Ohtsu A, Yoshida T, Saijo N, Kitamura Y, Kamatani N, Ozawa S, Sawada J (2004) Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population, Hum Mut, 23, 100.

3. Fukuda N, Ito Y, Yamaguchi M, Mitsumori K, Koizumi M, Hasegawa R, Kamata E, Ema M (2004) Unexpected nephrotoxicity induced by tetrabromobisphenol A in newborn rats. Toxicol Lett, 150, 145-155.

4. Kaniwa N, Aoyagi N (2004) Bioequivalence testing guideline for genetic drugs of topical application products. Iyakuhin Kenkyu, 35, 212-222. (Japanese)

5. Umemura T, Kitamura Y, Kanki K, Maruyama S, Okazaki K, Imazawa T, Nishimura T, Hasegawa R, Nishikawa A, Hirose M (2004) Dose-related changes of oxidative stress and cell proliferation in kidneys of male and female F344 rats exposed to potassium bromate. Cancer Sci, 95, 393-398.

6. Hasegawa R (2004) Fundamental research on proper use of medicine. Iyakuhin Kenkyu, 35, 265-279. (Japanese)

7. Sai K, Saeki M, Saito Y, Ozawa S, Katori N, Jinno H, Hasegawa R, Kaniwa N, Sawada J, Komamura K, Ueno K, Kamakura K, Kitakaze M, Kitamura Y, Kamatani N , Minami H, Ohtsu A, Shirao K, Yoshida T, Saijo N (2004) UGT1A1 haplotypes associated with reduced glucuronidation and increased serum bilirubin in irinotecan-administered Japanese patients with cancer. Clin Pharmacol Ther, 75, 501-515.

8. Hasegawa R, Koizumi M, Hirose A (2004) Principles of risk assessment for determining the safety of chemicals: Recent assessment of residual solvents in drugs and di(2-ethylhexyl) phthalate. Congenit Anom ( Kyoto ), 44, 51-59.

9. Urano T, Koizumi M, Saito M, Hasegawa R (2004) Investigation on drugs withdrawn from the market for safety reasons in foreign countries and the safety control action against these drugs in Japan. Pharmaceut Regul Sci, 35, 453-460. (Japanese)

10. Takahashi M, Hirata M, Matsumoto M, Hirose A, Kamata E, Hasegawa R, Ema M (2004) Progress of OECD chemicals programme. Bull Natl Inst Health Sci, 122, 37-42. (Japanese)

11. Takahashi M, Ogata H, Izumi H, Yamashita K, Takechi M, Hirata-Koizumi M, Kamata E, Hasegawa R, Ema M (2004) Comparative study of toxicity of 2,4,6-trinitrophenol (picric acid) in newborn and young rats. Congenit Anom ( Kyoto ), 44, 204-214.

12. Hirose A, Hasegawa R, Takahashi M, Nishikawa A, Ema M (2004) Revision and establishment of Japanese drinking water quality guidelines for di(ethylhexyl) phthalate, toluene and vinyl chloride - Differences from the latest WHO guideline drafts -. J Toxicol Sci, 29, 535-553.

2003

1. Hasegawa R (2003) Current risk assessment of chemicals for human health. Jpn Hyg PVC Assoc, 142, 5-18. (Japanese)

2. Connelly J, Osterberg RE, Tucker ML, Hasegawa R (2003) ICH Guideline Residual Solvents: Update. Pharmeuropa, 15, 365-372.

3. Koizumi M, Noda A, Ito Y, Furukawa M, Fujii M, Kamata E, Ema M, Hasegawa R (2003) Higher susceptibility of newborn than young rats to 3-methylphenol. J Toxicol Sci, 28, 59-70.

4. Hirose A, Ema M, Kamata A, Koizumi M, Hasegawa R (2003) Human Health Risk Assessment for the Endocrine Disruption Effects of Bisphenol A. Jpn J Food Chem, 10, 1-12.(Japanese)

5. Umemura T, Kai S, Hasegawa R, Kanki K, Kitamura Y, Nishikawa A, Hirose M (2003) Prevention of dual promoting effects of pentachlorophenol, an environmental pollutant, on diethylnitrosamine-induced hepato- and cholangio-carcinogenesis in mice by green tea infusion. Carcinogenesis, 24, 1105-1109.

6. Sai K, Kaniwa N, Itoda M, Saito Y, Hasegawa R, Komamura K, Ueno K, Kamakura S, Kitakaze M, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Kitamura Y, Kamatani N, Ozawa S, Sawada J (2003) Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan. Pharmacogenetics, 13, 741-754.

7. Oka T, Adati N, Shinkai T, Sakuma K, Nishimura T, Kurose K (2003) Bisphenol A Induces Apoptosis in Central Neural Cells During Early Development of Xenopus laevis. Biochem Biophys Res Commun, 312, 877-882.

8. Saeki M, Saito Y, Jinno H, Tohkin M, Kurose K, Kaniwa N, Komamura K, Ueno K, Kamakura S, Kitakaze M, Ozawa S, Sawada J (2003) Comprehensive UGT1A1 genotyping in a Japanese population by pyrosequencing. Clin Chem, 49, 1182-1185.

9. Ikeda S, Kurose K, Ozawa S, Sai K, Hasegawa R, Komamura K, Ueno K, Kamakura S, Kitakaze M, Tomoike H, Nakajima T, Matsumoto K, Saito H, Goto Y, Kimura H, Katoh M, Sugai K, Minami N, Shirao K, Tamura T, Yamamoto N, Minami H, Ohtsu A, Yoshida T, Saijo N, Saito Y, Sawada J (2003) Twenty-six novel single nucleotide polymorphisms and their frequencies of the NR1I3 (CAR) gene in a Japanese population. Drug Metab Pharmacokinet, 18, 413-418.

2002

1. Kojima S, Shimada H, Hashimoto M, Naeshiro I, Nakajima Y, Kadota T, Miyake Y, Morita T, Wakata A, Takeuchi M, Sakai K, Suzuki S, Matsuzawa T, Okuda H, Inoue T, Hayashi M, Hasegawa R, Okuda H, Takada K (2002) Questions and Answers on the Qualification of Impurities in Drug Substances and Drug Products. Iyakuhin Kenkyu, 33, 17-27. (Japanese)

2. Hirose A, Nishikawa A, Ema M, Kurebayashi H, Yamada M, Hasegawa R (2002) Toxicological Properties on Methyl tertiary-butyl Ether (MTBE). J Japan Soc Water Environ, 25, 491-496. (Japanese)

3. Koizumi M, Ohno Y, Hirose M, Ema M, Inoue T, Hasegawa R (2002) Toxicity evaluation of DINP and estimation of the tolerable daily intake. Jpn. J. Food Chem., 9, 39-45. (Japanese)

4. Koizumi M, Nishimura N, Enami T, Sunaga M, Horikawa H, Kamata E, Hasegawa R (2002) Comparative toxicity study of 3-aminophenol in newborn and young rats. J Toxicol Sci, 27, 411-421.

5. Koyano S, Kurose K, Ozawa S, Saeki M, Nakajima Y, Hasegawa R, Komamura K, Ueno K, Kamakura S, Nakajima T, Saito H, Kimura H, Goto Y, Saitoh O, Katoh M, Ohnuma T, Kawai M, Sugai K, Ohtsuki T, Suzuki C, Minami N, Saito Y, Sawada J (2002) Eleven novel single nucleotide polymorphisms in the NR112 (PXR) gene, four of which induce non-synonymous amino acid alterations. Drug Metabol Pharmacokinet, 17, SNP27 (561)-SNP31 (565).

6. Kaniwa N (2002) Variable factors and eligibility evaluation of dissolution test. Pharm Tech Japan , 18, 1865-1871. (Japanese)

7. Morihara M, Aoyagi N, Kaniwa N, Katori N, Kojim S. (2002) Hydrodynamic flows around tablets in different pharmacopeial dissolution tests. Drug Dev Ind Pharm, 28, 655-662.

8. Kaniwa N (2002) Japanese Perspectives on Pharmaceutical Product Release Rate Testing. Drug Inform J, 36, 407-415.

9. Sai K, Kaniwa N, Ozawa S, Sawada J (2002) An Analytical Method for Irinotecan (CPT-11) and its Metabolites using a High-performance Liquid Chromatography: Parallel Detection with Fluorescence and Mass Spectrometry. Biomed Chromat, 16, 209-218.

10. Tohkin M (2002) Regulation of Lipid Metabolism by LXR and FXR. Molecular Medicine, 39, 294-300. (Japanese)

11. Tohkin M, Sinal C, Miyata M, Gonzalez F (2002) Transcriptional Regulation of Cyp7a by Nuclear Receptor, FXR/BAR. Seikagaku, 73, 1489. (Japanese)