Clinical pharmacokinetic trials using limited sampling design and robust data analysis

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: University of Toyama
• Principal Investigator: HASHIMOTO Yukiya 富山大学, 大学院・医学薬学研究部(薬学), 教授 (90228429)
• Co-Investigator(Kenkyū-buntansha): NOZAWA Takashi 富山大学, 大学院・医学薬学研究部(医学), 准教授 (00180737) ; ICHIDA Fukiko 富山大学, 大学院・医学薬学研究部(医学), 准教授 (30223100) ; TAGUCHI Masato 富山大学, 大学院・医学薬学研究部(医学), 准教授 (20324056) ; ISHIDA Kazuya 富山大学, 大学院・医学薬学研究部(医学), 助教 (90550509)
• Project Period (FY): 2009 – 2011
• Keywords: 採血デザイン / 臨床薬物動態試験

Research Abstract

Evaluation of the relationship between pharmacological effect and blood concentration of the drug and investigation of the mechanisms for interindividual variability of the pharmacokinetics of the drug are needed to optimize the drug therapy for patients. Recently, we have clarified that the 3 step analysis is useful method to analyze the limited number of patients and/or data in the exploratory clinical trials. In the present study, we verified whether 3 step data analysis is useful to evaluate the pharmacokinetics of the drug in small or medium scale clinical trials

Research Products

• [Journal Article] Population pharmacokinetics of mizoribine in pediatric recipients of renal transplantation. (2012)
  • Author(s): Ishida K, Motoyama O, Shishido S, Tsuzuki K, and Hashimoto Y
  • Journal Title: Clin Exp. Nephrol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics of mizoribine in adult recipients of renal transplantation. (2011)
  • Author(s): Ishida K, Okamoto M, Ishibashi M, and Hashimoto Y
  • Journal Title: Clin Exp. Nephrol. Volume: 15 Pages: 900-906
  • Peer Reviewed
• [Journal Article] Effect of genetic polymorphisms of SLC28A1, ABCG2, and ABCC4 on bioavailability of mizoribine in healthy Japanese males (2011)
  • Author(s): Fukao M, Ishida K, Sakamoto T, Taguchi M, Matsukura H, Miyawaki T, and Hashimoto Y
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 26 Pages: 538-543
  • Peer Reviewed
• [Journal Article] Mechanisms for membrane transport of metformin in human intestinal epithelial Caco-2 cells (2011)
  • Author(s): Horie A, Sakata J, Nishimura M, Ishida K, Taguchi M, and Hashimoto Y
  • Journal Title: Biopharm. Drug Dispos. Volume: 32 Pages: 253-260
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of bosentan in routinely treated Japanese pediatric patients with pulmonary arterial hypertension (2011)
  • Author(s): Taguchi M, Ichida F, Hirono K, Miyawaki T, Yoshimura N, Nakamura T, Akita C, Nakayama T, Saji T, Kato Y, Horiuchi I, and Hashimoto Y
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 26 Pages: 280-27
  • Peer Reviewed
• [Journal Article] Effect of the VKORC1 genotype on warfarin dose requirements in Japanese pediatric patients (2011)
  • Author(s): Kato Y, Ichida F, Saito K, Watanabe K, Hirono K, Miyawaki T, Yoshimura N, Horiuchi I, Taguchi M, and Hashimoto Y
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 26 Pages: 295-299
  • Peer Reviewed
• [Journal Article] Membrane transport mechanisms of quinidine and procainamide in renal LLC-PK_1 and intestinal LS180 cells (2010)
  • Author(s): Masago M, Takaai M, Sakata J, Horie A, Ito T, Ishida K, Taguchi M, and Hashimoto Y
  • Journal Title: Biol. Pharm. Bull. Volume: 33 Pages: 1407-1412
  • Peer Reviewed
• [Journal Article] Inhibitory and stimulative effects of amiodarone on metabolism of carvedilol in human liver microsomes (2010)
  • Author(s): Horiuchi I, Kato Y, Nakamura A, Ishida K, Taguchi M, and Hashimoto Y
  • Journal Title: Biol. Pharm. Bull. Volume: 33 Pages: 717-720
  • Peer Reviewed
• [Journal Article] Temperature-dependent specific transport of levofloxacin in human intestinal epithelial LS180 cells (2009)
  • Author(s): Fukumori S, Masago M, Ishida K, Kayano Y, Taguchi M, and Hashimoto Y
  • Journal Title: Biopharm. Drug Dispos. Volume: 30 Pages: 448-456
  • Peer Reviewed
• [Journal Article] A simulation study to evaluate limited sampling strategies to estimate area under the curve of drug concentration versus time following repetitive oral dosing : limited sampling model versus naive trapezoidal method (2009)
  • Author(s): Kayano Y, Horiuchi I, Mori YI, Ishida K, Saito T, Taguchi M, and Hashimoto Y
  • Journal Title: Biol. Pharm. Bull. Volume: 32 Pages: 1486-1490
  • Peer Reviewed
• [Journal Article] Mechanisms responsible for the altered pharmacokinetics of bosentan : analysis utilizing rats with bile duct ligation-induced liver dysfunction (2009)
  • Author(s): Horiuchi I, Mori YI, Taguchi M, Ichida F, Miyawaki T, and Hashimoto Y
  • Journal Title: Biopharm. Drug Dispos. Volume: 30 Pages: 326-333
  • Peer Reviewed
• [Journal Article] Membrane transport mechanisms of mizoribine in the rat intestine and human epithelial LS180 cells (2009)
  • Author(s): Ishida K, Takaai M, Yotsutani A, Taguchi M, and Hashimoto Y
  • Journal Title: Biol. Pharm. Bull. Volume: 32 Pages: 741-745
  • Peer Reviewed
• [Journal Article] Involvement of the CYP1A subfamily in stereoselective metabolism of carvedilol inβ-naphthoflavone-treated Caco-2 cells (2009)
  • Author(s): Ishida K, Taguchi M, Akao T, and Hashimoto Y
  • Journal Title: Biol. Pharm. Bull. Volume: 32 Pages: 513-516
  • Peer Reviewed
• [Presentation] Effect of Genetic Polymorphisms of SLC28A1, ABCG2, and ABCC4 on Bioavailability of Mizoribine in Healthy Japanese Males (2011)
  • Author(s): Ishida K, Fukao M, Watanabe H, Taguchi M, Matsukura H, Miyawaki T, and Hashimoto Y
  • Organizer: 2011 American Association of Pharmaceutical Scientists Annual Meeting
  • Place of Presentation: Washington, D. C.
  • Year and Date: 20111123-27
• [Presentation] Effect of genetic polymorphisms of nucleoside and efflux transporters on bioavailability of mizoribine (2011)
  • Author(s): Fukao M, Ishida K, Taguchi M, Matsukura H, Miyawaki T, and Hashimoto Y
  • Organizer: 日本薬物動態学会第26年会
  • Place of Presentation: 広島
  • Year and Date: 20111116-18
• [Presentation] 培養ヒト腸上皮Caco-2細胞におけるメトホルミンの膜輸送機構 (2011)
  • Author(s): 堀江明日佳,西邑麻希,石田和也,坂田淳平,田口雅登,橋本征也
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: 東京
  • Year and Date: 20110529-31
• [Presentation] 培養ヒト腸上皮細胞を用いたミゾリビンの消化管吸収機構解析 (2011)
  • Author(s): 横田篤,森川真圭,石田和也,田口雅登,橋本征也
  • Organizer: 日本薬学会北陸支部第123回例会
  • Place of Presentation: 金沢
  • Year and Date: 2011-11-27
• [Presentation] 健常成人のミゾリビンの消化管吸収に対する遺伝と食塩摂取の影響 (2011)
  • Author(s): 深尾美紀,渡邉ひとみ,石田和也,田口雅登,橋本征也,松倉裕喜,宮脇利男
  • Organizer: 日本薬学会北陸支部第123回例会
  • Place of Presentation: 金沢
  • Year and Date: 2011-11-27
• [Presentation] 日本人小児患者のワルファリン投与量に及ぼすVKORC1遺伝子多型の影響 (2011)
  • Author(s): 田口雅登,市田蕗子,齋藤和由,渡邉一洋,芳村直樹,橋本征也
  • Organizer: 第12回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2011-06-17
• [Presentation] Optimal limited sampling designs to estimate maximal concentration and area under the curve of mizoribine in pediatric patients with renal disease (2010)
  • Author(s): Ishida K, Takaai M, Uemura O, Nagai T, Satomura K, Kaneda H, Ohta K, Fujieda M, Wada N, Goto Y, Morooka M, and Hashimoto Y
  • Organizer: Pharmaceutical Sciences World Congress 2010
  • Place of Presentation: New Orleans
  • Year and Date: 20101114-18
• [Presentation] Inhibitory and stimulative effects of amiodarone on stereoselective metabolism of carvedilol in human and rat liver microsomes (2010)
  • Author(s): Horiuchi I, Kato Y, Nakamura A, Ishida K, Taguchi M, and Hashimoto Y
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮
  • Year and Date: 20101007-09
• [Presentation] 小児腎疾患患者におけるミゾリビンの最適少数採血デザインの評価 (2010)
  • Author(s): 石田和也,鷹合麻里,上村治,永井琢人,里村憲一,金田尚,太田和秀,藤枝幹也,和田尚弘,後藤芳充,諸岡正史,橋本征也
  • Organizer: 医療薬学フォーラム2010
  • Place of Presentation: 広島
  • Year and Date: 20100710-11
• [Presentation] 小児腎疾患患者におけるミゾリビンのAUCとC_<max>予測のための最適少数採血デザインの評価 (2010)
  • Author(s): 石田和也,鷹合麻里,上村治,永井琢人,里村憲一,金田尚,太田和秀,藤枝幹也,和田尚弘,後藤芳充,諸岡正史,橋本征也
  • Organizer: 第45回日本小児腎臓病学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20100702-03
• [Presentation] 腸上皮LS180細胞を用いたプロカインアミドの膜輸送特性解析 (2010)
  • Author(s): 石田和也,真砂美希,坂田淳平,鷹合麻里,堀江明日佳,伊藤俊和,田口雅登、橋本征也
  • Organizer: 日本薬剤学会第25年会
  • Place of Presentation: 徳島
  • Year and Date: 20100512-14
• [Presentation] 腎上皮LLC-PK_1および腸上皮LS180細胞におけるプロカインアミドの膜輸送機構解析 (2010)
  • Author(s): 真砂美希,坂田淳平,西條早紀,鷹合麻里,堀江明日佳,伊藤俊和,石田和也,田口雅登,橋本征也
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 20100328-30
• [Presentation] ミゾリビンのバイオアベイラビリティの個体間変動機構 (2009)
  • Author(s): 四谷綾乃,鷹合麻里,坂本卓也,横田篤,堀内威佐男,石田和也,田口雅登,橋本征也,松倉裕喜
  • Organizer: 第30回臨床薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091203-05
• [Presentation] カルベジロールの立体選択的代謝に及ぼすアミオダロンの影響 (2009)
  • Author(s): 堀内威佐男,加藤悠也,中村有沙,石田和也,田口雅登,橋本征也
  • Organizer: 第30回臨床薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20091203-05
• [Presentation] Absorption mechanisms of mizoribine and ribavirin in rat intestine and human epithelial LS180 cells (2009)
  • Author(s): Ishida K, Yotsutani A, Sakamoto T, Takaai M, Taguchi M, and Hashimoto Y
  • Organizer: 日本薬物動態学会第24回年会
  • Place of Presentation: 京都
  • Year and Date: 20091127-29
• [Presentation] 胆管結紮誘発肝障害モデルラットを用いたボセンタンの体内動態変動機構解析 (2009)
  • Author(s): 田口雅登,堀内威佐男,森ゆんい,市田蕗子,宮脇利男,橋本征也
  • Organizer: 第19回日本医療薬学会
  • Place of Presentation: 長崎
  • Year and Date: 20091024-25
• [Presentation] 連投薬物のAUC推定におけるLimited sampling modelの有用性評価 (2009)
  • Author(s): 田口雅登,堀内威佐男,森ゆんい,萱野勇一郎,石田和也,橋本征也
  • Organizer: 医療薬学フォーラム
  • Place of Presentation: 京都
  • Year and Date: 20090711-12
• [Presentation] Limited sampling modelによる薬物連投時のAUC推定に対するシミュレーション評価 (2009)
  • Author(s): 堀内威佐男,森ゆんい,石田和也,萱野勇一郎,田口雅登,橋本征也
  • Organizer: 第26回日本TDM学会・学術大会
  • Place of Presentation: 新潟
  • Year and Date: 20090613-14
• [Presentation] 培養ヒト腸上皮Caco-2細胞を用いたメトトレキサートの消化管吸収機構解析 (2009)
  • Author(s): 鷹合麻里,坂田淳平,田和也,田口雅登,橋本征也
  • Organizer: 日本薬剤学会第24年会
  • Place of Presentation: 静岡
  • Year and Date: 20090521-23
• [Presentation] 薬物連投時のAUC推定におけるLimited Sampling Modelの精度評価 (2009)
  • Author(s): 堀内威佐男,森ゆんい,石田和也,萱野勇一郎,田口雅登,橋本征也
  • Organizer: 日本薬剤学会第24年会
  • Place of Presentation: 静岡
  • Year and Date: 20090521-23
• [Presentation] Caco-2細胞におけるカルベジロールの立体選択的代謝機構 (2009)
  • Author(s): 石田和也,田口雅登,赤尾光昭,橋本征也
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 20090326-28
• [Presentation] ラット小腸および培養ヒト腸上皮LS180細胞におけるミゾリビン膜輸送の特性解析 (2009)
  • Author(s): 鷹合麻里,石田和也,四谷綾乃,田口雅登,橋本征也
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 20090326-28
• [Presentation] LS180細胞を用いたミゾリビン小腸吸収の変動機構解析 (2009)
  • Author(s): 四谷綾乃,鷹合麻里,坂本卓也,横田篤,堀内威佐男,石田和也,田口雅登,松倉裕喜,橋本征也
  • Organizer: 日本薬学会北陸支部第121回例会
  • Place of Presentation: 富山
  • Year and Date: 2009-12-06
• [Presentation] 小児肺高血圧患者におけるボセンタンの体内動態変動性評価 (2009)
  • Author(s): 田口雅登,加藤悠也,堀内威佐男,橋本征也,廣野恵一,伊吹圭二郎,市田蕗子,芳村直樹,秋田千里,中村常之,中山智孝,佐地勉
  • Organizer: 第37回北陸小児肺循環研究会
  • Place of Presentation: 金沢
  • Year and Date: 2009-09-19
• [Presentation] 培養ヒト腸上皮Caco-2におけるメトトレキサートの経細胞輸送機構 (2009)
  • Author(s): 鷹合麻里,坂田淳平,石田和也,田口雅登,橋本征也
  • Organizer: 日本薬学会北陸支部第120回例会
  • Place of Presentation: 金沢
  • Year and Date: 2009-07-11
• [Presentation] 小児肺高血圧患者におけるボセンタンの体内動態解析 (2009)
  • Author(s): 田口雅登,森ゆんい,堀内威佐男,橋本征也,廣野恵一,上勢敬一郎,市田蕗子,芳村直樹,北岡千佳,中村常之,高月晋一,中山智孝,佐地勉
  • Organizer: 第15回日本小児肺循環研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-07