1992 Fiscal Year Final Research Report Summary
Ocular Pharmacokinetics: Computer Assisted In Vivo/In Vitro Correlation of Ocular Drug Delivery and Its Clinical Application
| Project/Area Number |
03454416
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | Kyushu Institute of Technology |
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Principal Investigator |
TOJO Kakuji Kyushu Institute of Technology Faculty of Computer Science and Systems Engineering. Professor, 情報工学部, 教授 (20081359)
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| Co-Investigator(Kenkyū-buntansha) |
OHTORI Akira Itami Research Laboratory, Senju Pharmaceutical Co. Researcher, 伊丹研究所, 研究員
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| Project Period (FY) |
1991 – 1992
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| Keywords | Ocular Pharmacokinetics / In vivo / in vitro correlation / Mathematical model / Corneal permeation / Vitreal pharmacokinetics / Ocular drug delivery |
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| 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.
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