Population pharmacokinetics and pharmacodynamics and individualized therapy in patients with refractory epilepsy

• Project/Area Number: 21590156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: YANO Ikuko 京都大学, 大学院・薬学研究科, 准教授 (50273446)
• Co-Investigator(Renkei-kenkyūsha): FUKUDO Masahide 京都大学, 大学院・医学研究科, 助教 (60437233)
• Research Collaborator: IKEDA Akio 京都大学, 大学院・医学研究科, 准教授 (90212761) ; MASUDA Satohiro 京都大学, 大学院・医学研究科, 講師 (90303825)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オーダーメイド医療 / 臨床薬物動態学 / 遺伝子 / 脳神経疾患 / 薬学 / 薬剤反応性 / 薬物動態学 / 薬物動態 / 薬力学 / P-糖タンパク質 / 遺伝学 / 母集団解析

Research Abstract

We quantitatively evaluated the effects of CYP2C19 genotype and co-administered antiepileptics on clobazam and N-desmethylclobazam pharmacokinetics. The high N-desmethylclobazam concentration in CYP2C19 poor metabolizers suggested a higher possibility of response to low-dose clobazam, and genotyping of CYP2C19 might be useful in individualized therapy with this drug.

Research Products

• [Journal Article] Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring (2012)
  • Author(s): Shibata M, Hashi S, Nakanishi H, Masuda S, Katsura T, Yano I
  • Journal Title: Biomed Chromatogr Volume: (in press) Issue: 12 Pages: 1519-1528
  • DOI: 10.1002/bmc.2726
  • Peer Reviewed
• [Journal Article] Significance of trough monitoring for tacrolimus blood concentration and calcineurin activity in adult patients undergoing primary living-donor liver transplantation (2012)
  • Author(s): Yano I, Masuda S, Egawa H, Sugimoto Y, Fukudo M, Yoshida Y, Hashi S, Yoshizawa A, Ogura Y, Ogawa K, Mori A, Kaido T, Uemoto S, Inui K
  • Journal Title: Eur J Clin Pharmacol Volume: 68(3) Issue: 3 Pages: 259-266
  • DOI: 10.1007/s00228-011-1129-x
  • NAID: 120003988188
  • Peer Reviewed
• [Journal Article] Degree of freezing does not affect efficacy of frozen gloves for prevention of docetaxel-induced nail toxicity in breast cancer patients (2012)
  • Author(s): Yano I, Ishiguro H, et al
  • Journal Title: Supportive Care in Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Degree of freezing does not affect efficacy of frozen gloves for prevention of do cetaxel-induced nail toxicity in breast cancer patients (2011)
  • Author(s): Ishiguro H(1番目), Yano I, Yanagihara K, et al
  • Journal Title: Support Care Cancer Volume: (in press) Issue: 9 Pages: 2017-2024
  • DOI: 10.1007/s00520-011-1308-4
  • NAID: 120004873705
  • Peer Reviewed
• [Journal Article] Heterozygous variants of multidrug and toxin extrusions(MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic patients (2010)
  • Author(s): Toyama K, Yonezawa A, Tsuda M, Masuda S, Yano I, Terada T, Osawa R, Katsura T, Hosokawa M, Fujimoto S, Inagaki N, Inui K
  • Journal Title: Pharmacogenet. Genomics Volume: 20(2) Issue: 2 Pages: 135-138
  • DOI: 10.1097/fpc.0b013e328335639f
  • Peer Reviewed
• [Journal Article] A transient increase of calcineurin phosphatase activity in living-donor kidney transplant recipients with acute rejection (2010)
  • Author(s): Fukudo M, Yano I, Katsura T, Ito N, Yamamoto S, Kamoto T, Ogawa O, Inui K
  • Journal Title: Drug Metab Pharmacokinet Volume: 25(5) Pages: 411-417
  • NAID: 10027583568
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of vancomycin after intravenous administration in 3 patients implanted with vancomycin-loaded cement beads. (2010)
  • Author(s): Shinsako, K., et al.
  • Journal Title: Jpn.J.Pharm.Care Sci. Volume: 36 Pages: 826-831
  • Peer Reviewed
• [Journal Article] A transient increase of calcineurin phosphatase activity in living-donor kidney transplant recipients with acute rejection. (2010)
  • Author(s): Fukudo, M., et al.
  • Journal Title: Drug Metab.Pharmacokinet. Volume: 25 Pages: 411-417
  • NAID: 10027583568
  • Peer Reviewed
• [Journal Article] Heterozygous variants of multidrug and toxin extrusions(MATE1 and MATE2-K)have little influence on the disposition of metformin in diabetic patients. (2010)
  • Author(s): Toyama K., et al.
  • Journal Title: Pharmacogenet. Genomics 20 Pages: 135-138
  • Peer Reviewed
• [Journal Article] Prospective evaluation of the Bayesian method for individualizing tacrolimus dose early after living-donor liver transplantation (2009)
  • Author(s): Fukudo M, Yano I, Shinsako K, Katsura T, Takada Y, Uemoto S, Inui K
  • Journal Title: J Clin Phamacol Volume: 49(7) Issue: 11 Pages: 789-797
  • DOI: 10.1002/jps.21731
  • Peer Reviewed
• [Journal Article] Effect of itraconazole on the pharmacokinetics of everolimus administered by different routes in rats (2009)
  • Author(s): Yokomasu A, Yano I, Sato E, Masuda S, Katsura T, Inui K
  • Journal Title: Biopharm Drug Disp Volume: 30(9) Issue: 9 Pages: 517-523
  • DOI: 10.1002/bdd.687
  • Peer Reviewed
• [Journal Article] Effect of itraconazole on the pharmacokinetics of everolimus administered by different routes in rats. (2009)
  • Author(s): Yokomasu, A., et al.
  • Journal Title: Biopharm. Drug Disp. 30 Pages: 517-523
  • Peer Reviewed
• [Journal Article] Population analysis of myelosuppression profiles using routine clinical data after combination cancer chemotherapy. (2009)
  • Author(s): Yano, Y., et al.
  • Journal Title: J.Pharm,Sci. 98 Pages: 4402-4412
  • Peer Reviewed
• [Journal Article] 薬物トランスポーター活用ライブラリー 機能・輸送基質から創薬・臨床応用まで(羊土社) (2009)
  • Author(s): 矢野育子
  • Journal Title: 羊土社 Pages: 169-171
• [Presentation] 難治性てんかん患者のクロバザム治療におけるCYP2C19遺伝子多型の寄与 (2011)
  • Author(s): 柴田茉衣、端幸代、増田智先、桂敏也、池田昭夫、松本理器、高橋良輔、矢野育子
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: アクトシティ浜松(静岡県)
  • Year and Date: 2011-12-01
• [Presentation] 抗てんかん薬の脳移行に及ぼす薬物排出トランスポータの影響 (2011)
  • Author(s): 中西晴香、柴田茉衣、桂敏也、矢野育子
  • Organizer: 第61回日本薬学会近畿支部総会
  • Place of Presentation: 大会、神戸学院大学(兵庫県)
  • Year and Date: 2011-10-22
• [Presentation] 抗てんかん薬の脳移行に及ぼす薬物排出トランスポータの影響 (2011)
  • Author(s): 矢野育子、中西晴香, ほか
  • Organizer: 第61回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸学院大学(兵庫県)
  • Year and Date: 2011-10-22
• [Presentation] Significance of trough monitoring of tacrolimus blood concentration and calcineurin activity in living-donor liver transplant patients (2011)
  • Author(s): Yano I, Masuda S, Egawa H, Sugimoto M, Fukudo M, Yoshida Y, Yasuda Y, Kaido T, Uemoto S, Inui K
  • Organizer: 12th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Place of Presentation: Stuttgart,(Germany)
  • Year and Date: 2011-10-05
• [Presentation] 新規抗てんかん薬ラモトリギンの血中濃度測定と相互作用に関する検討 (2011)
  • Author(s): 端幸代、矢野育子、増田智先、柴田茉衣、中西晴香、桂敏也、松本理器、池田昭夫、高橋良輔
  • Organizer: 第28回日本TDM学会・学術大会
  • Place of Presentation: 広島国際会議場(広島県)
  • Year and Date: 2011-06-18
• [Presentation] UPLC/MS/MS法を用いた抗てんかん薬一斉測定法の構築 (2010)
  • Author(s): 柴田茉衣、矢野育子、安田幸代、増田智先、桂敏也
  • Organizer: 第31回日本臨床薬理学会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2010-12-01
• [Presentation] UPLC/MS/MS法を用いた抗てんかん薬-斉測定法の構築 (2010)
  • Author(s): 柴田茉衣, ほか
  • Organizer: 第20回日本臨床薬理学会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2010-12-01
• [Presentation] Population pharmacokinetics and pharmacogenetics of clobazam and its active metabolite in Japanese adults with refractory epilepsy (2010)
  • Author(s): Yano I, Shibata M, Yasuda S, Yokomasu A, Hosohata K, Masuda S, Ikeda A, Takahashi R, Inui K
  • Organizer: WORLDPHARMA
  • Place of Presentation: Copenhagen,(Dan mark)
  • Year and Date: 2010-07-22
• [Presentation] Population pharmacokinetics and pharmacogenetics of clobazam and its active metabolite in Japanese adults with refractory epilepsy. (2010)
  • Author(s): Yano, I., et al.
  • Organizer: World Pharma 2010
  • Place of Presentation: Bella Center(Copenhagen)
  • Year and Date: 2010-07-22
• [Presentation] 抗てんかん薬クロバザム及び活性代謝物N-デスメチルクロバザム体内動態の母集団解析とファーマコゲノミクス (2009)
  • Author(s): 柴田茉衣, 矢野育子, 安田幸代, 横増晃, 細畑圭子, 増田智先, 池田昭夫, 高橋良輔, 乾賢一
  • Organizer: 第30回日本臨床薬理学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-03
• [Presentation] 成人難治性てんかん患者における低用量クロバザムの体内動態と臨床効果に与えるCYP2C19およびCYP3A5遺伝子多型の影響 (2009)
  • Author(s): 安田幸代、矢野育子、細畑圭子、増田智先、池田昭夫、高橋良輔、乾賢一
  • Organizer: 第26回日本TDM学会・学術大会
  • Place of Presentation: 朱鷺メッセ(新潟県)
  • Year and Date: 2009-06-14
• [Book] 最新薬剤学第10版 (2012)
  • Author(s): 矢野育子(分担執筆)
  • Total Pages: 605
  • Publisher: 廣川書店
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/