標的臓器における医薬品のPK/PD理論に基づいた治療最適化ソフトの構築と臨床応用

2010 年度 研究成果報告書

• 研究課題/領域番号: 20590146
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 医療系薬学
• 研究機関: 広島大学
• 研究代表者: 森川 則文 広島大学, 大学院・医歯薬学総合研究科, 教授 (30346481)
• 研究分担者: 猪川 和朗 広島大学, 大学院・医歯薬学総合研究科, 准教授 (40363048) ; 池田 佳代 広島大学, 大学院・医歯薬学総合研究科, 助教 (30379911)
• 研究期間 (年度): 2008 – 2010
• キーワード: 臨床 / 感染症 / 癌 / PK / PD

研究概要

我々は、研究協力病院において患者の血液および生体試料を収集する体制を構築した。送られた患者の生体試料中の薬物濃度を測定する方法を確立し、測定結果は、E-mailにて送付した。患者個々の薬物の薬物動態(PK)データと薬力学(PD)データを収集した。集めたPKデータから、母集団薬物動態パラメータ(PPK)を推定した。推定したPPKを用い、標的臓器における医薬品のPK/PD理論に基づいた治療最適化ソフトの構築と臨床応用を行った。

研究成果

• [雑誌論文] LC determination of total cefotiam concentration in human serum : application of ultrafiltration to a high protein-binding drug (2010)
  • 著者名/発表者名: Ikeda K, Ikawa K, Aoki S, Morikawa N, Takahashi S, Tsukamoto T
  • 雑誌名: Chromatographia 72 ページ: 157-162
  • 査読あり
• [雑誌論文] Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction (2010)
  • 著者名/発表者名: Matsumoto K, Takeshita A, Ikawa K, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Takeda Y, Yamada K
  • 雑誌名: Int.J.Antimicrob.Agents 36 ページ: 179-181
  • 査読あり
• [雑誌論文] Pharmacokinetic?pharmacodynamic target attainment analysis of meropenem in Japanese adult patients (2010)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ohge H, Ikeda K, Sueda T, Taniwaki M, Kurisu K
  • 雑誌名: J.Infect.Chemother. 16 ページ: 25-32
  • 査読あり
• [雑誌論文] Peritoneal pharmacokinetics and pharmacodynamic target attainment of meropenem in patients undergoing abdominal surgery (2010)
  • 著者名/発表者名: Soga Y, Ohge H, Ikawa K, Morikawa N, Ikeda K, Sueda T
  • 雑誌名: J.Chemother. 22 ページ: 98-102
  • 査読あり
• [雑誌論文] Penetration of doripenem into prostatic tissue after intravenous administration in prostatectomy patients (2010)
  • 著者名/発表者名: Yamada Y, Ikawa K, Nakamura K, Mitsui K, Narushima M, Hibi H, Ikeda K, Morikawa N, Honda N
  • 雑誌名: Int.J.Antimicrob.Agents 35 ページ: 504-506
  • 査読あり
• [雑誌論文] Population pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients (2010)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Miki M, Kobayashi M
  • 雑誌名: J.Infect.Chemother. 16 ページ: 139-143
  • 査読あり
• [雑誌論文] Determination of teicoplanin trough concentration target and appropriate total dose during the first 3 days : a retrospective study in patients with MRSA infections (2010)
  • 著者名/発表者名: Matsumoto K, Kanazawa N, Ikawa K, Fukamizu T, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Takeda Y, Yamada K
  • 雑誌名: J.Infect.Chemother. 16 ページ: 193-199
  • 査読あり
• [雑誌論文] HPLC method for measuring meropenem and biapenem concentrations in human peritoneal fluid and bile : application to comparative pharmacokinetic investigations (2010)
  • 著者名/発表者名: Kameda K, Ikawa K, Ikeda K, Morikawa N, Nakashima A, Ohge H, Sueda T
  • 雑誌名: J.Chromatogr.Sci. 48 ページ: 406-411
  • 査読あり
• [雑誌論文] Assessment of micafungin regimens by pharmacokineticpharmacodynamic analysis : a dosing strategy for Aspergillus infections (2010)
  • 著者名/発表者名: Ikawa K, Nomura K, Morikawa N, Ikeda K, Taniwaki M
  • 雑誌名: J.Antimicrob.Chemother. 64 ページ: 840-844
  • 査読あり
• [雑誌論文] Population pharmacokinetic modeling and pharmacodynamic assessment of cefozopran in pediatric patients (2010)
  • 著者名/発表者名: Ikawa K, Kozumi T, Ikeda K, Morikawa N, Kobayashi R
  • 雑誌名: Jpn.J.Antibiot. 62 ページ: 435-444
  • 査読あり
• [雑誌論文] Penetrability of intravenous biapenem into the peritoneal fluid of laparotomy patients and the peritoneal pharmacodynamics against Gram-negative bacteria (2009)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Sakashita M, Ohge H, Sueda T
  • 雑誌名: J.Appl.Res. 9 ページ: 107-112
  • 査読あり
• [雑誌論文] Pharmacokinetics and pharmacodynamics of once-daily arbekacin during continuous venovenous hemodiafiltration in critically ill patients (2009)
  • 著者名/発表者名: Ikawa K, Morikawa N, Suyama H, Ikeda K, Yamanoue T
  • 雑誌名: J.Infect.Chemother. 15 ページ: 420-423
  • 査読あり
• [雑誌論文] Pharmacokinetics and pharmacodynamics of biapenem in human cerebrospinal fluid (2009)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Katagiri M, Kiya K, Isobe N, Mizoue T, Kondo H, Takano M
  • 雑誌名: Int.J.Antimicrob.Agents 34 ページ: 184-185
  • 査読あり
• [雑誌論文] Determination of total cefozopran concentrations in human peritoneal fluid by HPLC with cefepime as an internal standard : comparative pharmacokinetics in the fluid and plasma (2009)
  • 著者名/発表者名: Ikeda K, Ikawa K, Morikawa N, Ohge H, Sueda T
  • 雑誌名: J.Pharm.Biomed.Anal. 49 ページ: 1075-1081
  • 査読あり
• [雑誌論文] Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes. (2009)
  • 著者名/発表者名: Matsumoto K, Ikawa K, Abematsu K, Fukunaga N, Nishida K, Fukamizu T, Shimodozono Y, Morikawa N, Takeda Y, Yamada K
  • 雑誌名: Int.J.Antimicrob.Agents 34 ページ: 91-94
  • 査読あり
• [雑誌論文] LC method for the determination of meropenem in cerebrospinal fluid : application to therapeutic drug monitoring (2009)
  • 著者名/発表者名: Matsuda T, Ikawa K, Ikeda K, Morikawa N, Tsumura R, Shibukawa M, Iida K, Kurisu K
  • 雑誌名: Chromatographia 69 ページ: 1031-1034
  • 査読あり
• [雑誌論文] Pharmacokinetic-pharmacodynamic target attainment analysis of doripenem in infected patients (2009)
  • 著者名/発表者名: Ikawa K, Morikawa N, Uehara S, Monden K, Yamada Y, Honda N, Kumon H
  • 雑誌名: Int.J.Antimicrob.Agents 33 ページ: 276-279
  • 査読あり
• [雑誌論文] Renal function as a predictor of linezolid-induced thrombocytopenia (2009)
  • 著者名/発表者名: Matsumoto K, Takeda Y, Ikawa K, Takeshita A, Fukunaga N, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Yamada K
  • 雑誌名: Int.J.Antimicrob.Agents 33 ページ: 98-99
  • 査読あり
• [雑誌論文] Pharmacokinetics and pharmacodynamics of biapenem in critically ill patients under continuous venovenous hemodiafiltration (2008)
  • 著者名/発表者名: Suyama H, Ikawa K, Morikawa N, Ikeda K, Fujiue Y, Morikawa S, Kaneko K, Kuwabara M, Yamanoue T
  • 雑誌名: Jpn.J.Antibiot. 61 ページ: 303-313
  • 査読あり
• [雑誌論文] Population pharmacokinetics of high-dose methotrexate in Japanese adult patients with malignancies : a concurrent analysis of the serum and urine concentration data (2008)
  • 著者名/発表者名: Fukuhara K, Ikawa K, Morikawa N, Kumagai K
  • 雑誌名: J.Clin.Pharm.Ther. 33 ページ: 677-684
  • 査読あり
• [雑誌論文] Is extended administration time and/or frequent administration of biapenem always effective? (2008)
  • 著者名/発表者名: Ikeda K, Ikawa K, Morikawa N, Doi M, Kuwabara M
  • 雑誌名: Jpn.J.Ther.Drug Monit. 25 ページ: 157-164
  • 査読あり
• [雑誌論文] Pharmacodynamic assessment of doripenem in peritoneal fluid against Gram-negative organisms : use of population pharmacokinetic modeling and Monte Carlo simulation (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • 雑誌名: Diagn.Microbiol.Infect.Dis. 62 ページ: 292-297
  • 査読あり
• [雑誌論文] Pharmacokinetic-pharmacodynamic target attainment analysis of biapenem in adult patients : a dosing strategy. (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T, Suyama H, Doi M, Kuwabara M
  • 雑誌名: Chemotherapy. 54 ページ: 386-394
  • 査読あり
• [雑誌論文] Pharmacodynamic evaluation of biapenem in peritoneal fluid using population pharmacokinetic modelling and Monte Carlo simulation (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • 雑誌名: Int.J.Antimicrob.Agents. 32 ページ: 339-343
  • 査読あり
• [雑誌論文] The pharmacokinetics and pharmacodynamic exposure of meropenem in the cerebrospinal fluid of neurosurgical patients (2008)
  • 著者名/発表者名: Tsumura R, Ikawa K, Morikawa N, Ikeda K, Shibukawa M, Iida K, Kurisu K
  • 雑誌名: J.Chemother. 20 ページ: 615-621
  • 査読あり
• [雑誌論文] Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • 雑誌名: J.Infect.Chemother. 14 ページ: 330-332
  • 査読あり
• [雑誌論文] Penetration and exposure of cefotiam into the peritoneal fluid of abdominal surgery patients after intravenous administration (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Fukuhara K, Hayato S, Ikeda K, Soga Y, Ohge H, Sueda T
  • 雑誌名: J.Chemother. 20 ページ: 319-323
  • 査読あり
• [雑誌論文] Considerations of meropenem dosage for bacterial meningitis based on pharmacodynamics in cerebrospinal fluid (2008)
  • 著者名/発表者名: Ikawa K, Tsumura R, Morikawa N, Ikeda K, Shibukawa M, Iida K, Kurisu K
  • 雑誌名: Int.J.Antimicrob.Agents 32 ページ: 96-98
  • 査読あり
• [雑誌論文] Quantification of doripenem in human plasma and peritoneal fluid by high-performance liquid chromatography with ultraviolet detection (2008)
  • 著者名/発表者名: Ikeda K, Ikawa K, Morikawa N, Kameda K, Urakawa N, Ohge H, Sueda T
  • 雑誌名: J.Chromatogr.B Analyt.Technol.Biomed.Life Sci. 867 ページ: 20-25
  • 査読あり
• [雑誌論文] Optimized dosage and frequency of cefozopran for patients with febrile neutropenia based on population pharmacokinetic and pharmacodynamic analysis (2008)
  • 著者名/発表者名: Nomura K, Morikawa N, Ikawa K, Ikeda K, Fujimoto Y, Shimizu D, Taniguchi K, Shimura K, Kanbayashi Y, Komori T, Matsumoto Y, Fujita N, Shimazaki C, Taniwaki M
  • 雑誌名: J.Antimicrob.Chemother. 61 ページ: 892-900
  • 査読あり
• [雑誌論文] Penetration into and exposure of cefozopran in pelvic retroperitoneal space exudate (2008)
  • 著者名/発表者名: Ikawa K, Mikamo H, Morikawa N, Ikeda K, Tamaya T
  • 雑誌名: J.Infect.Chemother. 14 ページ: 170-171
  • 査読あり
• [雑誌論文] Development of breakpoints of cephems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in the peritoneal fluid of patients (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • 雑誌名: J.Infect.Chemother. 14 ページ: 141-146
  • 査読あり
• [雑誌論文] Pharmacokinetic-pharmacodynamic target attainment analysis of cefozopran in Japanese adult patients (2008)
  • 著者名/発表者名: Ikawa K, Nomura K, Morikawa N, Ikeda K, Ohge H, Sueda T, Taniwaki M
  • 雑誌名: J.Infect.Chemother. 14 ページ: 130-136
  • 査読あり
• [雑誌論文] Peritoneal pharmacokinetics of cefepime in laparotomy patients with inflammatory bowel disease, and dosage considerations for surgical intra-abdominal infections based on pharmacodynamic assessment (2008)
  • 著者名/発表者名: Higuchi K, Ikawa K, Ikeda K, Ohge H, Sueda T, Houchi H, Morikawa N
  • 雑誌名: J.Infect.Chemother. 14 ページ: 110-116
  • 査読あり
• [雑誌論文] Population pharmacokinetics and pharmacodynamics of biapenem in paediatric patients (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Miki M, Nishimura S, Kobayashi M
  • 雑誌名: J.Clin.Pharm.Ther. 33 ページ: 203-210
  • 査読あり
• [雑誌論文] Pharmacokinetics and pharmacodynamic assessment of imipenem in the intraperitoneal fluid of abdominal surgery patients (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Sakamoto K, Ikeda K, Ohge H, Takesue Y, Sueda T
  • 雑誌名: Chemotherapy 54 ページ: 131-139
  • 査読あり
• [雑誌論文] Pharmacokinetic modeling and dosage adaptation of biapenem in Japanese patients during continuous venovenous hemodiafiltration (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Suyama H
  • 雑誌名: J.Infect.Chemother. 14 ページ: 35-39
  • 査読あり
• [学会発表] Clinical pharmacokinetics and pharmacodynamics of meropenem and biapenem in bile (2010)
  • 著者名/発表者名: Ikawa K, Nakashima A, Morikawa N, Ikeda K, Murakami Y, Ohge H, Derendorf H, Sueda T
  • 学会等名: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy
  • 発表場所: Boston, U.S.A
  • 年月日: 20100912-20100915
• [学会発表] Dexamethasone reduced voriconazole plasma level in a patient who carries CYP2C19 mutant (2009)
  • 著者名/発表者名: Matsumoto K, Kondo T, Kanazawa N, Yokoyama Y, Fukamizu T, Takeda Y, Mukai M, Arimura H, Nakazaki M, Ikawa K, Morikawa N, Tei C, Yamada K
  • 学会等名: Asian Federation for Pharmaceutical Sciences
  • 発表場所: Fukuoka, Japan
  • 年月日: 20091015-20091018
• [学会発表] Considerations of micafungin regimen for Candida and Aspergillus infections based on pharmacokineticpharmacodynamic target attainment analysis (2009)
  • 著者名/発表者名: Ikawa K, Nomura K, Morikawa N, Ikeda K, Taniwaki M
  • 学会等名: 49th Interscience Conference on Antimicrobial Agents and Chemotherapy
  • 発表場所: San Francisco, U.S.A
  • 年月日: 20090912-20090915
• [学会発表] Comparative pharmacokinetics and pharmacodynamics of meropenem, doripenem and imipenem in the peritoneal fluid and plasma of abdominal surgery patients (2008)
  • 著者名/発表者名: Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • 学会等名: 48th Interscience Conference on Antimicrobial Agents and Chemotherapy & 46th Annual Meeting of Infectious Diseases Society of America
  • 発表場所: Washington, DC, U.S.A
  • 年月日: 20081025-20081028
• [学会発表] Optimal administration method of cefepime for febrile neutropenia based on pharmacokinetic and pharmacodynamic findings (2008)
  • 著者名/発表者名: Nomura K, Fujimoto Y, Ohshiro M, Kanbayashi Y, Ikawa K, Morikawa N, Taniwaki M
  • 学会等名: 13th International Congress on Infectious Diseases
  • 発表場所: Kuala Lumpur, Malaysia
  • 年月日: 20080619-20090622