Optimization of antimicrobial therapy based on target-site pharmacokinetics and combined pharmacodynamics

• Project/Area Number: 24590659
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Hiroshima University
• Principal Investigator: IKAWA Kazuro 広島大学, 医歯薬保健学研究院(薬), 准教授 (40363048)
• Co-Investigator(Kenkyū-buntansha): MORIKAWA Norifumi 広島大学, 医歯薬保健学研究院(薬), 教授 (30346481) ; IKEDA Kayo 広島大学, 医歯薬保健学研究院(薬), 助教 (30379911)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 臨床 / 感染症 / 薬物動態 / 薬力学

Outline of Final Research Achievements

This research project aimed to particularly optimize combination antimicrobial therapy for multidrug-resistant bacteria, with pharmacokinetic model analysis of drug concentrations in target organs or infection sites, and pharmacodynamic assessment of combined antimicrobial effects. The research project was able to evaluate combined effects of double and triple antimicrobial drugs in vitro against multidrug-resistant Pseudomonas aeruginosa clinical isolates. The research project also monitored concentrations of combination antimicrobial drugs in target sites of patients, and developed target-organ pharmacokinetic models. After computer tools were created for pharmacokinetic-pharmacodynamic modeling and simulation, the effective validity of combination colistin regimens, for infections with multidrug-resistant Pseudomonas aeruginosa, were quantitatively assessed.

Research Products

• [Journal Article] Clinical pharmacokinetics of meropenem in pancreatic juice and site-specific pharmacodynamic target attainment against Gram-negative bacteria: dosing considerations. (2014)
  • Author(s): Kondo N, Ikawa K, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Ohge H, Morikawa N, Sueda T.
  • Journal Title: Pancreatology Volume: 14 Issue: 2 Pages: 95-99
  • DOI: 10.1016/j.pan.2014.02.002
  • Peer Reviewed
• [Journal Article] Analysis of thrombocytopenic effects and population pharmacokinetics of linezolid: a dosage strategy according to the trough concentration target and renal function in adult patients. (2014)
  • Author(s): Matsumoto K, Shigemi A, Takeshita A, Watanabe E, Yokoyama Y, Ikawa K, Morikawa N, Takeda Y.
  • Journal Title: Int. J. Antimicrob. Agents Volume: 44 Issue: 3 Pages: 242-247
  • DOI: 10.1016/j.ijantimicag.2014.05.010
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamic target attainment of intravenous pazufloxacin in the bile of patients undergoing biliary pancreatic surgery. (2014)
  • Author(s): Uegami S, Ikawa K, Ohge H, Nakashima A, Shigemoto N, Morikawa N, Murakami Y, Sueda T.
  • Journal Title: J. Chemother. Volume: 26 Issue: 5 Pages: 287-292
  • DOI: 10.1179/1973947814y.0000000167
  • Peer Reviewed
• [Journal Article] Nephrotoxicity Induced by Piperacillin–Tazobactam in Late Elderly Japanese Patients with Nursing and Healthcare Associated Pneumonia (2014)
  • Author(s): Karino F, Nishimura N, Ishihara N, Moriyama H, Miura K, Hamaguchi S, Sutani A, Kuraki T, Ikawa K, Morikawa N, Naora K, Isobe T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 37 Issue: 12 Pages: 1971-1976
  • DOI: 10.1248/bpb.b14-00362
  • NAID: 130004693807
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Continuous ampicillin infusion as an alternative to intermittent infusion for adult inpatients: a case series. (2014)
  • Author(s): Ogawa T, Kasahara K, Ikawa K, Shigeta J, Komatsu Y, Kuruno N, Uno K, Maeda K, Mikasa K.
  • Journal Title: J. Infect. Chemother. Volume: 20 Issue: 10 Pages: 653-655
  • DOI: 10.1016/j.jiac.2014.05.006
  • Peer Reviewed
• [Journal Article] 臨床分離薬剤耐性緑膿菌に対する抗菌薬 in vitro 併用効果～colistin, arbekacin, aztreonam, rifampicin, piperacillin の 2 剤組合せを用いた比較検討～. (2014)
  • Author(s): 長岡里枝, 猪川和朗, 小野寺一, 木場由美子, 原稔典, 城市由美子, 横崎典哉, 大毛宏喜, 森川則文.
  • Journal Title: Jpn. J. Antibiot. Volume: 67 Pages: 167-174
  • NAID: 40020132098
  • Peer Reviewed
• [Journal Article] Pharmacokinetic modeling of serum and bronchial concentrations for clarithromycin and telithromycin, and site-specific pharmacodynamic simulation for their dosages. (2014)
  • Author(s): Ikawa K, Kikuchi E, Kikuchi J, Nishimura M, Derendorf H, Morikawa N.
  • Journal Title: J. Clin. Pharm. Ther. Volume: 39 Issue: 4 Pages: 411-417
  • DOI: 10.1111/jcpt.12157
  • Peer Reviewed
• [Journal Article] Penetration of meropenem into human pancreatic juice. (2013)
  • Author(s): Ikawa K, Kondo N, Nakashima A, Yoshizawa K, Morikawa N, Ikeda K, Murakami Y, Ohge H, Sueda T.
  • Journal Title: Scand. J. Infect. Dis. Volume: 45 Issue: 5 Pages: 404-406
  • DOI: 10.3109/00365548.2012.738936
  • Peer Reviewed
• [Journal Article] Population pharmacokinetic-pharmacodynamic target attainment analysis of imipenem plasma and urine data in neonates and children. (2013)
  • Author(s): Yoshizawa K, Ikawa K, Ikeda K, Ohge H, Morikawa N.
  • Journal Title: Pediatr. Infect. Dis. J. Volume: 32 Issue: 11 Pages: 1208-1216
  • DOI: 10.1097/inf.0b013e31829b5880
  • Peer Reviewed
• [Journal Article] Prostatic penetration of meropenem in humans, and dosage considerations for prostatitis based on a site-specific pharmacokinetic/pharmacodynamic evaluation. (2013)
  • Author(s): Nishikawa G, Ikawa K, Nakamura K, Yamada Y, Zennami K, Mitsui K, Narushima M, Ikeda K, Morikawa N, Sumitomo M.
  • Journal Title: Int. J. Antimicrob. Agents Volume: 41 Pages: 267-271
  • Peer Reviewed
• [Journal Article] 多剤耐性緑膿菌に対する抗菌薬3剤のin vitro併用効果 (2012)
  • Author(s): 木場由美子，猪川和朗，小野寺一，長岡里枝，原稔典，城市由美子，横崎典哉，大毛宏喜，森川則文
  • Journal Title: 日化療会誌 Volume: 60 Pages: 469-477
  • NAID: 10030787977
  • Peer Reviewed
• [Journal Article] Determination of doripenem penetration into human prostate tissue and assessment of dosing regimens for prostatitis based on site-specific pharmacokinetic-pharmacodynamic evaluation. (2012)
  • Author(s): Nakamura K, Ikawa K, Yamada Y, Arakawa M, Zennami K, Nishikawa G, Ikeda K, Morikawa N, Honda N.
  • Journal Title: J. Chemother. Volume: 24 Pages: 32-37
  • Peer Reviewed
• [Presentation] Prostatic penetration of pazufloxacin in humans, and dosage considerations for prostatitis based on a site-specific pharmacokinetic/pharmacodynamic evaluation. (2015)
  • Author(s): Nakamura K, Ikawa K, Nishikawa G, Kobayashi I, Zennami K, Kajikawa K, Yoshizawa T, Kato Y, Watanabe M, Narushima M, Kento K, Morikawa N, Sumitomo M.
  • Organizer: 30th Annual Congress of the European Association of Urology
  • Place of Presentation: Madrid, Spain
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] 薬剤耐性緑膿菌に対するコリスチン単剤・併用投与法の PK-PD 検討. (2014)
  • Author(s): 横山雄太, 猪川和朗, 長岡里枝, 小野寺一, 木場由美子, 原稔典, 横崎典哉, 大毛宏喜, 森川則文.
  • Organizer: 第 62 回日本化学療法学会西日本支部総会・第 57 回日本感染症学会中日本地方会学術集会・第 84 回日本感染症学会西日本地方会学術集会
  • Place of Presentation: 岡山市
  • Year and Date: 2014-10-23 – 2014-10-25
• [Presentation] Penetration of piperacillin-tazobactam into human prostate: dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics. (2014)
  • Author(s): Kobayashi I, Ikawa K, Nakamura K, Nishikawa G, Kajikawa K, Yoshizawa T, Watanabe M, Kato Y, Zennami K, Kanao K, Yamada Y, Mitsui K, Narushima M, Morikawa N, Sumitomo M.
  • Organizer: 34th Congress of the Societe Internationale d'Urologie
  • Place of Presentation: Glasgow, UK
  • Year and Date: 2014-10-12 – 2014-10-15
• [Presentation] 臨床ファーマコメトリクスに基づく voriconazole の個別化投薬～PGx-PK-PD 母集団モデルの構築とシミュレーションツールの開発～. (2014)
  • Author(s): 猪川和朗, 松元一明, 茂見茜里, 金澤直子, 渡辺英里香, 右川博明, 横山雄太, 森川則文, 武田泰生.
  • Organizer: 第 24 回日本医療薬学会年会
  • Place of Presentation: 名古屋市
  • Year and Date: 2014-09-27 – 2014-09-28
• [Presentation] PK-PD ツール構築による抗 MRSA 薬 (VCM、TEIC、ABK、LZD、DAP) の適正投与への取り組み～ガイドラインの実践支援～. (2014)
  • Author(s): 石原慎之, 西村信弘, 猪川和朗, 右川博明, 森川則文, 直良浩司.
  • Organizer: 第 31 回日本 TDM 学会学術大会
  • Place of Presentation: 東京都
  • Year and Date: 2014-05-31 – 2014-06-01
• [Presentation] Biliary pharmacokinetics and pharmacodynamic target attainment of intravenous pazufloxacin in surgery patients. (2013)
  • Author(s): Uegami S, Ohge H, Ikawa K, Shigemoto N, Nakashima A, Ikeda K, Morikawa N, Sueda T.
  • Organizer: 28th International Congress of Chemotherapy and Infection & 14th Asia-Pacific Congress of Clinical Microbiology and Infection
  • Place of Presentation: Yokohama, Japan
• [Presentation] Clinical pharmacokinetics of doripenem and meropenem in prostate tissue, and dosing considerations for prostatitis based on site-specific pharmacodynamic target attainment. (2013)
  • Author(s): Ikawa K, Nakamura K, Nishikawa G, Yamada Y, Zennami K, Mitsui K, Narushima M, Ikeda K, Morikawa N, Sumitomo M.
  • Organizer: 13th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Place of Presentation: Salt Lake City, USA
• [Presentation] Colistin の多剤耐性緑膿菌に対する in vitro 併用効果. (2013)
  • Author(s): 長岡里枝, 猪川和朗, 小野寺一, 木場由美子, 原稔典, 横崎典哉, 大毛宏喜, 森川則文.
  • Organizer: 第 61 回日本化学療法学会総会・第 87 回日本感染症学会学術講演会
  • Place of Presentation: 横浜
• [Presentation] Prostatic penetration of meropenem in humans, and dosage considerations for prostatitis based on site-specific pharmacokinetic-pharmacodynamic evaluation. (2013)
  • Author(s): Nishikawa G, Ikawa K, Nakamura K, Yamada Y, Zennami K, Ikeda K, Morikawa N, Sumitomo M.
  • Organizer: 28th Annual Congress of the European Association of Urology
  • Place of Presentation: Milan, Italy
• [Presentation] Pharmacokinetic modeling of cefepime concentration data in human lung and target-organ-specific pharmacodynamic simulation. (2012)
  • Author(s): Ikawa K, Iida S, Morikawa N.
  • Organizer: 1st World Conference on Pharmacometrics
  • Place of Presentation: Seoul, Korea
• [Presentation] Clinical pharmacokinetics and pharmacodynamics of clarithromycin and telithromycin in epithelial lining fluid of the bronchi. (2012)
  • Author(s): Ikawa K, Kikuchi E, Kikuchi J, Nishimura M, Derendorf H, Morikawa N.
  • Organizer: 41st Annual Meeting of the American College of Clinical Pharmacology
  • Place of Presentation: San Diego, USA