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Ocular Pharmacokinetics: Computer Assisted In Vivo/In Vitro Correlation of Ocular Drug Delivery and Its Clinical Application

Research Project

Project/Area Number 03454416
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionKyushu Institute of Technology

Principal Investigator

TOJO Kakuji  Kyushu Institute of Technology Faculty of Computer Science and Systems Engineering. Professor, 情報工学部, 教授 (20081359)

Co-Investigator(Kenkyū-buntansha) OHTORI Akira  Itami Research Laboratory, Senju Pharmaceutical Co. Researcher, 伊丹研究所, 研究員
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsOcular Pharmacokinetics / In vivo / in vitro correlation / Mathematical model / Corneal permeation / Vitreal pharmacokinetics / Ocular drug delivery / in vivo / 眼内薬物濃度予測
Research Abstract

The objective of this research project was to develop a general mathematical model for the ocular pharmacokinetics by which we can predict the concentration in the eye tissues following topical instillation.The mathematical model are also able to optimize the ocular drug delivery systems as well as to avoid possible undesired side effects. The software package for solving the ocular pharmacokinetic model has been developed in either DOS/V based personal computers or UNIX workstations.
The present ocular pharmacokinetic model comprises the precorneal tear flow dynamics, corneal diffusion/bioconversion and distribution/elimination in the aqueous humor and the surrounding tissues. The method for solving the pharmacokinetic model in order to evaluate the drug concentration in the internal eye tissues does not depend upon the curve fitting approach which has usually been applied in the literature. Instead, the model parameters can be determined from the independent in vitro experiments in a well-designed apparatus with respect to fluid dynamics; the diffusion coefficients and the partition coefficient in the cornea, the vitreous body, the lens and the retina/choroid/sclera membrane have been determined from the in vitro permeation experiments using the isolated tissues. The concentration-time profiles in the internal eye tissues such as the aqueous humor and the lens following topical instillation of various ocular drugs have been predicted from the present ocular pharmacokinetic model together with the model parameters determined independently.
Although the in vivo/in vitro correlation for ocular drug delivery proposed has been confirmed in the animal model (Japanese albino and pigmented rabbits), the clinical profiles can also be simulated by taking into consideratoin the differences in the structure and functions between the animal model and the human eyes.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 東條 角治: "眼科DDSにおける眼内薬物動態" あたらしい眼科. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Tojo: "A General Software Package (PCSOP) for Analyzing the Pharmacokinetics of Ophthalmic Drug Delivery" International Symposium on Advanced Computing for Life-Science. 305-306 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 大鳥 聡: "眼圧降下剤チモロールの眼内移行:In vivo/In vitro相関" あたらしい眼科. 9. 1398-1400 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 大鳥 聡: "薬物の角膜および強膜透過におよぼす種差の影響ーIn vitro透過実験による評価ー" あたらしい眼科. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Tojo: "In vivo/In vitro correlation of intravitreal drug delivery" Proceed.Intern.Symp.Control.Rel.Bioact.Mater.20. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 宇野 久美子: "疑似硝子体(ヒアルロン酸ゲル)内薬物挙動" あたらしい眼科. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Tojo and A. Ohtori: "Pharmacokinetics in the ocular delivery of drugs" J. of the Eye. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Uno, A. Ohtori and K. Tojo: "Drug transport in sodium hyaluratesimulated vitreous body" J. of the Eye. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Tojo and A. Ohtori: "A general software package (PCSOP) for analyzing the pharmacokinetics of ophthalmic drug delivery" Proceeding of International Symposium on Advanced Computing for Life-Science. ISKIT92. 305-306 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A. Ohtori and K. Tojo: "In vivo/in vitro correlation of timolol following topical instillation" J. of the Eye. 9. 1398-1400 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Tojo and A. Ohtori: "In vivo/in vitro correlation of intravitreal drug delivery" Proceed. Intern. Symp. Control. Rel. Bioact. Mater.20. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Tojo: "Pharmacokinetics of ophthalmic drug delivery" Proceeding of Ocular Pharmacology of Japan. 12. 107-110 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 東條 角治: "眼科DDSにおける眼内薬物動態" あたらしい眼科. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Tojo: "A General Software Package (PCSOP)for Analyzing the pharmacokinetics of Ophthalmic Drug Delivery" International Symposium on Advanced Computing for Life-Science. 305-306 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 大鳥 聡: "眼圧降下剤チモロールの眼内移行:In vivo/In vitro相関" あたらしい眼科. 9. 1398-1400 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 大鳥 聡: "薬物の角膜および強膜透過におよぼす種差の影響-In vitro透過実験による評価-" あたらしい眼科. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Tojo: "In vivo/In vitro correlation of intravitreal drug delivery" Proceed.Intern.Symp.Control.Rel.Bioact.Mater.20. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 宇野 久美子: "擬似硝子体(ヒアルロン酸ゲル)内薬物挙動" あたらしい眼科. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 大島 聡,東條 角治: "チモロ-ルの眼内移行:In vivo/in vitro相関" あたらしい眼科.

    • Related Report
      1991 Annual Research Report
  • [Publications] 東條 角治,大鳥 聡,森田 泰司: "眼内薬物タ-ゲティング:硝子体内挙動" 薬剤学. 51. 40-41 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Tojo and A.Othori: "Lens Pharmacokinetics" Proceedings of the International Congress of Eye Research.

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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