教員プロフィール

桒原 隆

桒原 隆

桒原 隆

Kuwabara Takashi

臨床薬学科/薬物動態学研究室[バイオ医薬品評価部門](教授)

最終学歴

京都大学薬学研究科博士前期過程(修士)

取得学位
薬学博士(東京大学)
所属学会

日本薬物動態学会(代議員)、日本薬学会

現在の専門分野

薬物動態学、薬物代謝学、医薬品開発論

現在の研究課題
  • タンパク質医薬品の薬物動態、開発論
主要研究業績
  • G-CSF誘導体ノイアップ(ナルトグラスチム)の薬物動態における受容体介在性クリアランスの影響
  • α1酸性糖タンパク質への強固な結合が薬物動態に及ぼす影響
  • アレロック錠(オロパタジン)の薬物動態
最近の研究業績 (2000年以降の原著論文)
  1. J. Hosogi, R. Ohashi , H. Maeda, K.Fujita, J. Ushiki, T. Kuwabara, Y. Yamamoto and T.Imamura., An iminium ion metabolite hampers the production of the pharmacologically active metabolite of a multikinase inhibitor KW-2449 in primates: irreversible inhibition of aldehyde oxidase and covalent binding with endogenous proteins., Biopharm Drug Dispos. 2018 Mar;39(3):164-174.
  2. J. Hosogi, R. Ohashi, H. Maeda, S. Tashiro, E. Fuse, Y. Yamamoto and T. Kuwabara., Monoamine oxidase B oxidizes a novel multikinase inhibitor KW-2449 to its iminium ion and aldehyde oxidase further converts it to the oxo-piperazine form in human.,Drug Metab Pharmacokinet. 2017 Oct;32(5):255-264.
  3. J. Hosogi, H. Tanaka, K. Fujita, T. Kuwabara, S. Ikegawa, N. Kobayashi, N. Mano and J. Goto, LC-MS/MS coupled with immunoaffinity extraction for determination of estrone, 17β-estradiol and estrone 3-sulfate in human plasma, J. Chromatogr. B 878, 222-227, 2010
  4. N. Mimura, Y. Nagata, T. Kuwabara and E. Fuse; P-glycoprotein limits the brain penetration of olopatadine hydrochloride, H1-receptor antagonist, Drug Metab. Pharmacokin., 23, 106-114, 2008
  5. K. Iwashita, H. Kawasaki, M. Sawada, M. In, Y. Mataki and T.Kuwabara, Shortening of the induction period of allergic asthma in cynomolgus monkeys by ascaris suum and house dust mite, J. Pharmacol. Sci., 106, 92-99, 2008
  6. K. Fujita, H. Kodaira, T. Kuwabara and H. Kobayashi, Pharmacokinetics and metabolism of KW-4490, a selective phosphodiesterase 4 inhibitor: difference in excretion of KW-4490 and acylglucuronide metabolites between rats and cynomolgus monkeys, Xenobiotica, 37, 1-16,2007
  7. Y. Sugiyama, N. Mimura, T. Kuwabara, H. Kobayashi, J. Ushiki and E. Fuse, effect of benidipine on simvastatin metabolism in human liver microsomes, Drug Metab. Pharmaokinet., 22, 199-205, 2007
  8. R. Tanaka, A. Rubio, N.K. Harn, D. Gernert, T.A. Grese, J. Eishima, M. Hara, N. Yoda, R. Ohashi, T. Kuwabara, S. Soga, S. Nara and Y. Kanda; Design and syanthesis of piperidine farnesyl transferase inhibitors with reduced glucuronidation potential, Bioorg. Med. Chem., 15, 1363-1382, 2007
  9. E. Fuse, T. Kuwabara, A. Sparreboom, E.A. Sauseville, W.D. Figg, Review of UCN-01 Development: A lesson in the importance of clinical pharmacology, J. Clin. Pharmacol., 45, 394-403, 2005
  10. T. Saeki, K. Eguchi, S. Takashima, T. Sugiura, T. Hida, N. Horikoshi, K. Aiba, T. Kuwabara and M. Ogawa: Phase I and pharmacokinetic study of KW-2170, a novel pyrazoloacridone compound, in patients with malignant tumors, Cancer Chemother. Phamacol., 54,459-468, 2004
  11. J. Kajita, E. Fuse T. Kuwabara and H. Kobayashi; The contribution of cytochrome P450 to the metabolism of tegafur in human liver, Drug Metab. Pharmacokin., 18, 303-309, 2003
  12. J. Kajita, K. Inano, E. Fuse T. Kuwabara and H. Kobayashi; Effects of olopatadine, a new antiallergic agent, on human liver microsomal cytochrome P450 activities., Drug Metab. Dispos., 30, 1504-1511, 2002
  13. T. Kuramitsu, K. Takai, R. Ohashi and T. Kuwabara: Determination of the anticancer drug KW-2170, a pyrazoloacridone derivative, and its metabolites in human and dog plasma by high-performance liquid chromatogarphy using an electrochemical detector, J. Chromato., 768, 231-237, 2002
  14. E.A. Sausville, S.G. Arbuck, R. Messmann, D. Headlee, K.S. Bauer, R.M. Lush, A. Murgo, W.D. Figg, T. Lahusen, S. Jaken, X. Jing, M. Roberge, E. Fuse, T. Kuwabara and A.M. Sendrowicz; Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory Neoplasmas, J. Clin. Oncol., 19:2319-2333, 2001
  15. K. Yasoshima, T. Kuwabara, E. Fuse, T. Kuramitsu, N. Kurata, H. Nishiie, T. Oishi, H. Kobayashi and S. Kobayashi: Phamacokinetics, distribution, metabolism and excretion of 3H-UCN-01 in rats and dogs after intravenous administration, Cancer Chemother. Phamacol., 47, 106-112, 2001
  16. Y. Kato, T. Kuwabara, T. Itoh, M. Hiura, A. Hatori, A. Shigematsu and T. Hara, A possible relationship between abortions and placental embolism in pregnant rabbits given human granulocyte colony-stimulating factor, J. Toxcol. Sci., 26, 39-50, 2001
  17. E. Fuse, A. Hashimoto, N. Sato, H. Tanii, T. Kuwabara, S. Kobayashi and Y. Sugiyama: Physiological modeling of altered pharmacokinetics of a novel anticancer drug, UCN-01(7-hydoxystaurosporine), caused by slow dissociation of UCN-01 from human a1-acid glycoprotein, Pharm. Res.. 17: 553-564, 2000
  18. N. Kurata, S. Imabeppu, M. Nitoh, H. Kobayashi, T. Kuwabara and S. Kobayashi: The effect of different dosing scgedules of UCN-01 on its pharmacokinetics and cardiohaemodynamics in dogs, J. Pharm. Pharmacol., 52, 1427-1335, 2000
  19. J. Kajita, T. Kuwabara, H. Kobayashi and S. Kobayashi; CYP3A4 is mainly responsible for the metabolism of a new vinca alkaloid, vinorelbine, in human liver microsomes. Drug Metab. Dispos., 28, 1121-1127, 2000
著書 (2000年以降)
  1. 桒原 隆、山崎基生、G-CSFの性状、15-29、コロニー刺激因子(CSF)の臨床、現状と未来、元吉和夫、浦部晶夫編、日本医学館、2001
招待講演 (2000年以降)
  1. 桒原 隆、ヒト化抗CCR4抗体モガムリズマブおよびそのコンパニオン診断薬の開発、日本薬剤学会年会、学術シンポジウム、2015
  2. 桒原 隆、抗体医薬品のpharmacokinetic/pharmacodynamics、薬物動態談話会年会、2014
  3. 桒原 隆、ヒト化抗CCR4抗体モガムリズマブおよびそのコンパニオン診断薬の開発、探索臨床研究会、2014
  4. 桒原 隆、 G-CSF誘導体ナルトグラスチムの開発、バイオロジクスフォーラム、2005
  5. Takashi Kuwabara;Clinical pharmacokinetics of a novel anticancerdrug, UCN-01: high affinity binding to humanα1-acid glycoprotein governs its pharmacokinetics、International symposium on serum albumin and α1-acid glycoprotein, 2000