Pharmacokinetic modeling and penetration enhancement of the percutaneous drug absorption based on diffusion theory
| Project/Area Number |
02670977
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
HASHIDA Mitsuru Kyoto University, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (20135594)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAKURA Yoshinobu Kyoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (30171432)
YAMAMOTO Akira Kyoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (00166779)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Percutaneous absorption / Skin model / Diffusion theory / Fast inverse Laplace transformation / Absorption enhancer / Skin penetration / Drug lipophilicity / In vitro diffusion experiments |
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| Research Abstract |
Two-layer skin model considering the first stratum corneum layer with polar and nonpolar routes and the second viable epidermis plus dermis layer was constructed and the corresponding transformed equations in the infinite and finite dose systems were derived from the Fick's diffusion low. By employing the inversion of these image equations to the real time course by the fast inverse Laplace transform(FILT)algorithm, absorption behavior of drugs were analyzed from physicochemical viewpoint. Using this system, the effects of different doses of 1-geranyl-azacycloheptan-2-one(GACH)on the in vitro penetration of seven drugs with various lipophilicities through the guinea pig skin were examined and its action mechanism wasdiscussed in terms of the partitioning and diffusivity of drugs in each domain. It was suggested that GACH mainly affects on the nonpolar route of the stratum corneum by changing its property as a solvent. The effects of d-limonen and oleic acid were also analyzed and the were concluded to enhance drug absorption by increasing the diffusivity of the drug in the stratum corneum. A skin diffusion model corresponding to in vivo condition was also constructed and relationship between in vitro and in vivo data was discussed based on these models.
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Report
(3 results)
Research Products
(15 results)
