| Project/Area Number |
12672216
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
KUROSAKI Yuji Okayama University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90161786)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Hiromu Okayama University, Graduate School of Natural Science and Technology, Professor, 大学院・自然科学研究科, 教授 (60125151)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | drug delivery system (DDS) / local pharmacokinetics / local bioavailability / microdialysis / lipo-microdialysis / percutaneous absorption / colonic absorption / zero-net-flux / 潰瘍性大腸炎 / 薬動学 / 薬力学 |
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| Research Abstract |
1 Estiniation of local bioavailability for locally acting drug delivery systems by pharmacokinetic- and pharmacodynamic-measurement was studied.
1. Application of microdialysis (MD) to measure local pharmacokinetic study
(1) Relative recovery, which is the barrier to apply MD in pharmacokinetic study, was strikingly improved by utilizing the lipid emulsions for intravenous injection as the perfusate (Lipo-MD). Both the reliability and the following-up characteristics in Zero-Net-Flux method were improved by the application of Lipo-MD (Lipo-ZNF method) in percutaneous permeation study using butylparaben as the model compound in rats.
(2) A MD system was introduced in the in situ closed loop method for studying gastrointestinal absorption study and named Intra-Loop-MD method. This method enabled to get pharmacokinetic parameters in each individual and to reduce the number of experimental animals significantly. The usefulness of this method in estimating populations containing the higher int
… More
erindividual variation was suggested.
2. Kinetic analysis of pharamacological response-time data for estimating local pharmacodynamic availability
The usefulness of a kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating (ductus-dilating) effect of lipo-PGE_1 (lipid emulsion preparation of prostaglandin E_1 for injection) preparations The ductus-dilating effect of lipo-PGE_1 in an infusion study was simulated by the same PRK model and the estimated parameters in the i.v.-study. The simulation line satisfactorily represented the time-course of the pharmacological response. These findings indicate that PRK modeling based on the intensities of the observed pharmacological response is a meaningful tool in some targeting-type drugs, for which pharmacokinetic analysis itself is meaningless or acquisition of pharmacokinetic data is technically impossible, in expecting the time courses of its pharmacological response in different dosage regimens. Less
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