Making and clinical application of supporting software for the optimal administration method of drug based on the PK/PD theory on the target-organ

• Project/Area Number: 20590146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Hiroshima University
• Principal Investigator: MORIKAWA Norifumi Hiroshima University, 大学院・医歯薬学総合研究科, 教授 (30346481)
• Co-Investigator(Kenkyū-buntansha): IKAWA Kazurou 広島大学, 大学院・医歯薬学総合研究科, 准教授 (40363048) ; IKEDA Kayo 広島大学, 大学院・医歯薬学総合研究科, 助教 (30379911)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 臨床 / 感染症 / 癌 / PK / PD / PK/PD

Research Abstract

We made a new system which collected blood and biological samples in patient at our research collaboration hospitals. It established the drug concentration measurement methods of those delivered samples of patients. Those measured drug concentration results were sent to the research collaboration hospitals by e-mail. It collected the pharmacokinetic (PK) and the pharmacodynamics (PD) data of drug in each patient. It estimated the population pharmacokinetic parameter (PPK) from the gathered individual PK data. We made the supporting software for the optimal administration method of drug based on the PK/PD theory on the target-organ used by the estimated PPK.

Research Products

• [Journal Article] LC determination of total cefotiam concentration in human serum : application of ultrafiltration to a high protein-binding drug (2010)
  • Author(s): Ikeda K, Ikawa K, Aoki S, Morikawa N, Takahashi S, Tsukamoto T
  • Journal Title: Chromatographia 72 Pages: 157-162
  • Peer Reviewed
• [Journal Article] Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction (2010)
  • Author(s): Matsumoto K, Takeshita A, Ikawa K, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Takeda Y, Yamada K
  • Journal Title: Int.J.Antimicrob.Agents 36 Pages: 179-181
  • Peer Reviewed
• [Journal Article] Pharmacokinetic?pharmacodynamic target attainment analysis of meropenem in Japanese adult patients (2010)
  • Author(s): Ikawa K, Morikawa N, Ohge H, Ikeda K, Sueda T, Taniwaki M, Kurisu K
  • Journal Title: J.Infect.Chemother. 16 Pages: 25-32
  • NAID: 10027189210
  • Peer Reviewed
• [Journal Article] Peritoneal pharmacokinetics and pharmacodynamic target attainment of meropenem in patients undergoing abdominal surgery (2010)
  • Author(s): Soga Y, Ohge H, Ikawa K, Morikawa N, Ikeda K, Sueda T
  • Journal Title: J.Chemother. 22 Pages: 98-102
  • Peer Reviewed
• [Journal Article] Penetration of doripenem into prostatic tissue after intravenous administration in prostatectomy patients (2010)
  • Author(s): Yamada Y, Ikawa K, Nakamura K, Mitsui K, Narushima M, Hibi H, Ikeda K, Morikawa N, Honda N
  • Journal Title: Int.J.Antimicrob.Agents 35 Pages: 504-506
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics and pharmacodynamics of meropenem in Japanese pediatric patients (2010)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Miki M, Kobayashi M
  • Journal Title: J.Infect.Chemother. 16 Pages: 139-143
  • NAID: 10027189654
  • Peer Reviewed
• [Journal Article] Determination of teicoplanin trough concentration target and appropriate total dose during the first 3 days : a retrospective study in patients with MRSA infections (2010)
  • Author(s): Matsumoto K, Kanazawa N, Ikawa K, Fukamizu T, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Takeda Y, Yamada K
  • Journal Title: J.Infect.Chemother. 16 Pages: 193-199
  • NAID: 10027189903
  • Peer Reviewed
• [Journal Article] HPLC method for measuring meropenem and biapenem concentrations in human peritoneal fluid and bile : application to comparative pharmacokinetic investigations (2010)
  • Author(s): Kameda K, Ikawa K, Ikeda K, Morikawa N, Nakashima A, Ohge H, Sueda T
  • Journal Title: J.Chromatogr.Sci. 48 Pages: 406-411
  • Peer Reviewed
• [Journal Article] Assessment of micafungin regimens by pharmacokineticpharmacodynamic analysis : a dosing strategy for Aspergillus infections (2010)
  • Author(s): Ikawa K, Nomura K, Morikawa N, Ikeda K, Taniwaki M
  • Journal Title: J.Antimicrob.Chemother. 64 Pages: 840-844
  • Peer Reviewed
• [Journal Article] Population pharmacokinetic modeling and pharmacodynamic assessment of cefozopran in pediatric patients (2010)
  • Author(s): Ikawa K, Kozumi T, Ikeda K, Morikawa N, Kobayashi R
  • Journal Title: Jpn.J.Antibiot. 62 Pages: 435-444
  • NAID: 10026274988
  • Peer Reviewed
• [Journal Article] Peritoneal pharmacokinetics and pharmacodynamic target attainment of meropenem in patients undergoing abdominal surgery. (2010)
  • Author(s): Soga Y, Ohge H, Ikawa K, Morikawa N, Ikeda K, Sueda T.
  • Journal Title: J.Chemother. Volume: 22 Pages: 98-102
  • Peer Reviewed
• [Journal Article] Pharmacokinetic-pharmacodynamic target attainment analysis of meropenem in Japanese adult patients. (2010)
  • Author(s): Ikawa K, Morikawa N, Ohge H, Ikeda K, Sueda T, Taniwaki M, Kurisu K
  • Journal Title: J.Infect.Chemother. Volume: 16 Pages: 25-32
  • NAID: 10027189210
  • Peer Reviewed
• [Journal Article] Penetration of doripenem into prostatic tissue after intravenous administration in prostatectomy patients. (2010)
  • Author(s): Yamada Y, Ikawa K, Nakamura K, Mitsui K, Narushima M, Hibi H, Ikeda K, Morikawa N, Honda N.
  • Journal Title: Int.J.Antimicrob.Agents Volume: 35 Pages: 504-505
  • Peer Reviewed
• [Journal Article] Penetrability of intravenous biapenem into the peritoneal fluid of laparotomy patients and the peritoneal pharmacodynamics against Gram-negative bacteria (2009)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Sakashita M, Ohge H, Sueda T
  • Journal Title: J.Appl.Res. 9 Pages: 107-112
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of once-daily arbekacin during continuous venovenous hemodiafiltration in critically ill patients (2009)
  • Author(s): Ikawa K, Morikawa N, Suyama H, Ikeda K, Yamanoue T
  • Journal Title: J.Infect.Chemother. 15 Pages: 420-423
  • NAID: 10027189089
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of biapenem in human cerebrospinal fluid (2009)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Katagiri M, Kiya K, Isobe N, Mizoue T, Kondo H, Takano M
  • Journal Title: Int.J.Antimicrob.Agents 34 Pages: 184-185
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): Ikeda K, Ikawa K, Morikawa N, Ohge H, Sueda T
  • Journal Title: J.Pharm.Biomed.Anal. 49 Pages: 1075-1081
  • Peer Reviewed
• [Journal Article] Correlation between voriconazole trough plasma concentration and hepatotoxicity in patients with different CYP2C19 genotypes. (2009)
  • Author(s): Matsumoto K, Ikawa K, Abematsu K, Fukunaga N, Nishida K, Fukamizu T, Shimodozono Y, Morikawa N, Takeda Y, Yamada K
  • Journal Title: Int.J.Antimicrob.Agents 34 Pages: 91-94
  • Peer Reviewed
• [Journal Article] LC method for the determination of meropenem in cerebrospinal fluid : application to therapeutic drug monitoring (2009)
  • Author(s): Matsuda T, Ikawa K, Ikeda K, Morikawa N, Tsumura R, Shibukawa M, Iida K, Kurisu K
  • Journal Title: Chromatographia 69 Pages: 1031-1034
  • Peer Reviewed
• [Journal Article] Pharmacokinetic-pharmacodynamic target attainment analysis of doripenem in infected patients (2009)
  • Author(s): Ikawa K, Morikawa N, Uehara S, Monden K, Yamada Y, Honda N, Kumon H
  • Journal Title: Int.J.Antimicrob.Agents 33 Pages: 276-279
  • Peer Reviewed
• [Journal Article] Renal function as a predictor of linezolid-induced thrombocytopenia (2009)
  • Author(s): Matsumoto K, Takeda Y, Ikawa K, Takeshita A, Fukunaga N, Shigemi A, Yaji K, Shimodozono Y, Morikawa N, Yamada K
  • Journal Title: Int.J.Antimicrob.Agents 33 Pages: 98-99
  • Peer Reviewed
• [Journal Article] Assessment of micafungin regimens by pharmacokinetic-pharmacodynamic analysis : a dosing strategy for Aspergillus infections (2009)
  • Author(s): Ikawa K, Nomura K, Morikawa N, Ikeda K, Taniwaki M.
  • Journal Title: J Antimicrob Chemother 64(4) Pages: 840-844
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of biapenem in human cerebrospinal fluid (2009)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Katagiri M, Kiya K, Isobe N, Mizoue T, Kondo H, Takano M.
  • Journal Title: Int J Antimicrob Agents 34(2) Pages: 184-185
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of once-daily arbekacin during continuous venovenous hemodiafiltration in critically ill patients (2009)
  • Author(s): Ikawa K, Morikawa N, Suyama H, Ikeda K, Yamanoue T.
  • Journal Title: J Infect Chemother 15(6) Pages: 420-423
  • NAID: 10027189089
  • Peer Reviewed
• [Journal Article] Pharmacokinetic-pharmacodynamic target attainment analysis of doripenem in infected patients. (2009)
  • Author(s): Ikawa K, Morikawa N, Uehara S, Monden K, Yamada Y, Honda N, Kumon H.
  • Journal Title: Int. J. Antimicrob. Agents 33 Pages: 276-279
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of biapenem in critically ill patients under continuous venovenous hemodiafiltration (2008)
  • Author(s): Suyama H, Ikawa K, Morikawa N, Ikeda K, Fujiue Y, Morikawa S, Kaneko K, Kuwabara M, Yamanoue T
  • Journal Title: Jpn.J.Antibiot. 61 Pages: 303-313
  • NAID: 10024351503
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics of high-dose methotrexate in Japanese adult patients with malignancies : a concurrent analysis of the serum and urine concentration data (2008)
  • Author(s): Fukuhara K, Ikawa K, Morikawa N, Kumagai K
  • Journal Title: J.Clin.Pharm.Ther. 33 Pages: 677-684
  • Peer Reviewed
• [Journal Article] Is extended administration time and/or frequent administration of biapenem always effective? (2008)
  • Author(s): Ikeda K, Ikawa K, Morikawa N, Doi M, Kuwabara M
  • Journal Title: Jpn.J.Ther.Drug Monit. 25 Pages: 157-164
  • Peer Reviewed
• [Journal Article] Pharmacodynamic assessment of doripenem in peritoneal fluid against Gram-negative organisms : use of population pharmacokinetic modeling and Monte Carlo simulation (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • Journal Title: Diagn.Microbiol.Infect.Dis. 62 Pages: 292-297
  • Peer Reviewed
• [Journal Article] Pharmacokinetic-pharmacodynamic target attainment analysis of biapenem in adult patients : a dosing strategy. (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T, Suyama H, Doi M, Kuwabara M
  • Journal Title: Chemotherapy. 54 Pages: 386-394
  • Peer Reviewed
• [Journal Article] Pharmacodynamic evaluation of biapenem in peritoneal fluid using population pharmacokinetic modelling and Monte Carlo simulation (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • Journal Title: Int.J.Antimicrob.Agents. 32 Pages: 339-343
  • Peer Reviewed
• [Journal Article] The pharmacokinetics and pharmacodynamic exposure of meropenem in the cerebrospinal fluid of neurosurgical patients (2008)
  • Author(s): Tsumura R, Ikawa K, Morikawa N, Ikeda K, Shibukawa M, Iida K, Kurisu K
  • Journal Title: J.Chemother. 20 Pages: 615-621
  • Peer Reviewed
• [Journal Article] Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • Journal Title: J.Infect.Chemother. 14 Pages: 330-332
  • NAID: 10022595586
  • Peer Reviewed
• [Journal Article] Penetration and exposure of cefotiam into the peritoneal fluid of abdominal surgery patients after intravenous administration (2008)
  • Author(s): Ikawa K, Morikawa N, Fukuhara K, Hayato S, Ikeda K, Soga Y, Ohge H, Sueda T
  • Journal Title: J.Chemother. 20 Pages: 319-323
  • Peer Reviewed
• [Journal Article] Considerations of meropenem dosage for bacterial meningitis based on pharmacodynamics in cerebrospinal fluid (2008)
  • Author(s): Ikawa K, Tsumura R, Morikawa N, Ikeda K, Shibukawa M, Iida K, Kurisu K
  • Journal Title: Int.J.Antimicrob.Agents 32 Pages: 96-98
  • Peer Reviewed
• [Journal Article] Quantification of doripenem in human plasma and peritoneal fluid by high-performance liquid chromatography with ultraviolet detection (2008)
  • Author(s): Ikeda K, Ikawa K, Morikawa N, Kameda K, Urakawa N, Ohge H, Sueda T
  • Journal Title: J.Chromatogr.B Analyt.Technol.Biomed.Life Sci. 867 Pages: 20-25
  • NAID: 10028000189
  • Peer Reviewed
• [Journal Article] Optimized dosage and frequency of cefozopran for patients with febrile neutropenia based on population pharmacokinetic and pharmacodynamic analysis (2008)
  • Author(s): 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
  • Journal Title: J.Antimicrob.Chemother. 61 Pages: 892-900
  • Peer Reviewed
• [Journal Article] Penetration into and exposure of cefozopran in pelvic retroperitoneal space exudate (2008)
  • Author(s): Ikawa K, Mikamo H, Morikawa N, Ikeda K, Tamaya T
  • Journal Title: J.Infect.Chemother. 14 Pages: 170-171
  • NAID: 10021193889
  • Peer Reviewed
• [Journal Article] Development of breakpoints of cephems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in the peritoneal fluid of patients (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • Journal Title: J.Infect.Chemother. 14 Pages: 141-146
  • NAID: 10021193776
  • Peer Reviewed
• [Journal Article] Pharmacokinetic-pharmacodynamic target attainment analysis of cefozopran in Japanese adult patients (2008)
  • Author(s): Ikawa K, Nomura K, Morikawa N, Ikeda K, Ohge H, Sueda T, Taniwaki M
  • Journal Title: J.Infect.Chemother. 14 Pages: 130-136
  • NAID: 10021193738
  • Peer Reviewed
• [Journal Article] Peritoneal pharmacokinetics of cefepime in laparotomy patients with inflammatory bowel disease, and dosage considerations for surgical intra-abdominal infections based on pharmacodynamic assessment (2008)
  • Author(s): Higuchi K, Ikawa K, Ikeda K, Ohge H, Sueda T, Houchi H, Morikawa N
  • Journal Title: J.Infect.Chemother. 14 Pages: 110-116
  • NAID: 10021193668
  • Peer Reviewed
• [Journal Article] Population pharmacokinetics and pharmacodynamics of biapenem in paediatric patients (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Miki M, Nishimura S, Kobayashi M
  • Journal Title: J.Clin.Pharm.Ther. 33 Pages: 203-210
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamic assessment of imipenem in the intraperitoneal fluid of abdominal surgery patients (2008)
  • Author(s): Ikawa K, Morikawa N, Sakamoto K, Ikeda K, Ohge H, Takesue Y, Sueda T
  • Journal Title: Chemotherapy 54 Pages: 131-139
  • Peer Reviewed
• [Journal Article] Pharmacokinetic modeling and dosage adaptation of biapenem in Japanese patients during continuous venovenous hemodiafiltration (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Suyama H
  • Journal Title: J.Infect.Chemother. 14 Pages: 35-39
  • NAID: 10021193195
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and pharmacodynamics of biapenem in critically ill patients under continuous venovenous hemodiafiltration. (2008)
  • Author(s): Suyama H, Ikawa K, Morikawa N, Ikeda K, Fujiue Y, Morikawa S, Kaneko K, Kuwabara M, Yamanoue T.
  • Journal Title: Jpn. J. Antibiot. 61 Pages: 303-313
  • NAID: 10024351503
  • Peer Reviewed
• [Journal Article] Pharmacokinetic-pharmacodynamic target attainment analysis of biapenem in adult patients : a dosing strategy. (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T, Suyama H, Doi M, Kuwabara M.
  • Journal Title: Chemotherapy. 54 Pages: 386-394
  • Peer Reviewed
• [Presentation] Clinical pharmacokinetics and pharmacodynamics of meropenem and biapenem in bile (2010)
  • Author(s): Ikawa K, Nakashima A, Morikawa N, Ikeda K, Murakami Y, Ohge H, Derendorf H, Sueda T
  • Organizer: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy
  • Place of Presentation: Boston, U.S.A
• [Presentation] Dexamethasone reduced voriconazole plasma level in a patient who carries CYP2C19 mutant (2009)
  • Author(s): 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
  • Organizer: Asian Federation for Pharmaceutical Sciences
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Considerations of micafungin regimen for Candida and Aspergillus infections based on pharmacokineticpharmacodynamic target attainment analysis (2009)
  • Author(s): Ikawa K, Nomura K, Morikawa N, Ikeda K, Taniwaki M
  • Organizer: 49th Interscience Conference on Antimicrobial Agents and Chemotherapy
  • Place of Presentation: San Francisco, U.S.A
• [Presentation] Comparative pharmacokinetics and pharmacodynamics of meropenem, doripenem and imipenem in the peritoneal fluid and plasma of abdominal surgery patients (2008)
  • Author(s): Ikawa K, Morikawa N, Ikeda K, Ohge H, Sueda T
  • Organizer: 48th Interscience Conference on Antimicrobial Agents and Chemotherapy & 46th Annual Meeting of Infectious Diseases Society of America
  • Place of Presentation: Washington, DC, U.S.A
• [Presentation] Optimal administration method of cefepime for febrile neutropenia based on pharmacokinetic and pharmacodynamic findings (2008)
  • Author(s): Nomura K, Fujimoto Y, Ohshiro M, Kanbayashi Y, Ikawa K, Morikawa N, Taniwaki M
  • Organizer: 13th International Congress on Infectious Diseases
  • Place of Presentation: Kuala Lumpur, Malaysia