Ocular Pharmacokinetic/Pharmacodynamic Modeling for Multiple Anti-glaucoma Drugs

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概要

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• We have constructed a new ocular pharmacokinetic pharmacodynamic (PK/PD) model for anti-glaucomadrugs to describe ocular hypotensive effects on intraocular pressure (IOP) after instillation of a combination ofan a1-adrenergic antagonist, bunazosin, and a b -adrenergic antagonist, timolol, into rabbits. This model wasconstructed by the combination of two ocular PK/PD models for bunazosin and timolol by including aqueoushumor dynamics based on both action mechanisms. We also verified the reliability of this model by confirmingthe drug concentrations in aqueous humor and ocular hypotensive effects after instillation of the drug combination.The aqueous humor concentrations of timolol and bunazosin were determined by an HPLC, and ocular hypotensiveeffect-time profiles were measured using a telemetry system, which was able to record automaticallydetailed effects. The combined model could simulate the aqueous humor concentrations of both drugs and theadditive IOP-lowering effect after instillation of the combination using the MULTI (RUNGE) program andPK/PD parameters which were obtained from ocular hypotensive effects after instillation of bunazosin alone ortimolol alone. The theoretical concentration curves of both drugs in the aqueous humor and the theoretical ocularhypotensive effect curves almost agreed with both the observed concentrations and ocular hypotensive effectsafter instillation of the drug combination. These results indicate the reliability and usefulness of PK/PD modelingconsidering aqueous humor dynamics to predict IOP in multidrug therapy. This is the first study to develop aPK/PD model for multidrug therapy for the eye.

• 社団法人日本薬学会の論文
• 2008-08-01

著者

• Kawabata S

  Second Dep. Of Internal Medicine Nagasaki Univ. School Of Medicine

• Kohno Shigeru

  長崎大学 医学部第二内科

• 中島 幹夫

  佐賀大学医学部附属病院 手術部

• 中島 幹夫

  佐賀医科大学手術部

• Kamihira Shimeru

  長崎大学 医歯薬学総合研究科臨床検査医学講座

• 上平 憲

  長崎大学臨床検査医学

• Sugahara Kazuyuki

  Dep. Of Lab. Medicine Nagasaki Univ. Graduate School Of Biomedical Sciences Nagasaki Univ. Hospital

• Sugahara Kazuyuki

  長崎大学 医歯薬学総合研究科臨床検査医学講座

• Kawakami S

  Santen Pharmaceutical Co. Ltd. Nara Research And Development Center:department Of Hospital Pharmacy

• Kawakami Shigeru

  京都大学 薬学研究科

• Kawakami Shigeru

  Dep. Of Drug Delivery Res. Graduate School Of Pharmaceutical Sciences Kyoto Univ.

• Kohno Shigeru

  長崎大学医学部歯学部附属病院 薬剤部

• Kohno Shigeru

  Nagasaki University

• Kawakami S

  Department Of Laboratory Medicine Nagasaki University Graduate School Of Biomedical Sciences

• Sugahara Yazuyuki

  長崎大学 医歯薬学総合研究科臨床検査医学講座

• 中村 純三

  Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.

• Sugahara Yazuyuki

  Dep. Of Lab. Medicine Nagasaki Univ. Graduate School Of Biomedical Sciences Nagasaki Univ. Hospital

• Kohno Shigeru

  長崎大学 第二内科

• Kanazawa Shigeo

  公立みつぎ総合病院

• SASAKI Hitoshi

  Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry

• Nakamura J

  Faculty Of Pharmaceutical Sciences Nagasaki University

• Nakamura Junzo

  長崎大学 薬

• Nakamura Junzo

  School Of Pharmaceutical Sciences Nagasaki University

• Nishida K

  Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.

• Nakashima M

  Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.

• Nakashima M

  Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry

• Hara Shintaro

  長崎大学 医学部第二内科

• Kawabata S

  Santen Pharmaceutical Co. Ltd. Nara Research And Development Center:department Of Hospital Pharmacy

• Sasaki H

  Dep. Of Hospital Pharmacy Nagasaki Univ. Hospital

• NAKASHIMA MIKIRO

  Graduate School of Biomedical Sciences, Nagasaki University

• NAKAMURA JUNZO

  Graduate School of Biomedical Sciences, Nagasaki University

• NISHIDA KOYO

  Graduate School of Biomedical Sciences, Nagasaki University

• SAKANAKA Koji

  Santen Pharmaceutical Co., Ltd.Nara Research and Development Center

• KAWAZU Kouichi

  Santen Pharmaceutical Co., Ltd.Nara Research and Development Center.

• TOMONARI Masahide

  Department of Hospital Pharmacy, Nagasaki University School of Medicine

• KITAHARA Takashi

  Department of Hospital Pharmacy, Nagasaki University School of Medicine

• HIGUCHI Shun

  Graduate School of Pharmaceutical Sciences, Kyushu University

• Sakanaka Koji

  参天製薬奈良研究開発センター

• Kawazu Kouichi

  Santen Pharmaceutical Co. Ltd. Nara Research And Development Center

• Kitahara Takashi

  花王生物科学研究所

• Tsukahara Kazue

  Global R&d Biological Science Kao Corporation

• Tomonari Masahide

  Department Of Hospital Pharmacy Nagasaki University School Of Medicine

• Nakano M

  Department Of Laboratory Medicine Nagasaki University School Of Medicine

• Sasaki Hitoshi

  長崎大学 医歯学部病院薬剤部

• Sasaki Hitoshi

  Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University

• Shiota H

  Nagasaki Univ. Nagasaki Jpn

• Sasaki Hajime

  Semiconductor Group Mitsubishi Electric Corporation

• KITAHARA Takashi

  Kao Corporation Biological Science Laboratories

• Sasaki Hideyuki

  R&d Center Toshiba Corp.

• Kohno Shigeru

  Second Department Of Internal Medicine Nagasaki University School Of Mediciene

• 上平 憲

  長崎大学医学部臨床検査医学

• Kobayashi Kazuko

  Santen Pharmaceutical Co. Ltd. Nara Research And Development Center

• Kashiwagi Satsuki

  School Of Pharmaceutical Sciences Nagasaki University

• Sasaki H

  Central Research Laboratories Zeria Pharmaceutical Co. Ltd.

• Sasaki H

  Electrotechnical Laboratory

• Sakanaka Koji

  Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry:santen Pharma

• Higuchi Shun

  Dep. Of Clinical Pharmacokinetics Graduate School Of Pharmaceutical Sciences Kyushu Univ.

• Kitahara Takashi

  Department Of Breast Surgery Cancer Institute Hospital

• Sasaki H

  Nagasaki Univ. School Of Medicine Nagasaki Jpn

• Tsukahara Kazue

  Biological Science Laboratories Kao Corporation

• Kitahara Takashi

  Biological Science Laboratories Kao Corporation

• Nishida Koyo

  Graduate School Of Biomedical Sciences Nagasaki Univ.

• Kitahara Takashi

  Department Of Breast Oncology Cancer Institute Hospital Of Japanese Foundation For Cancer Research

• Sasaki Hitoshi

  Department Of Hospital Pharmacy Nagasaki University Hospital

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