RRC ID |
45100
|
著者 |
Baek IH, Lee BY, Chae JW, Song GY, Kang W, Kwon KI.
|
タイトル |
Development of a pharmacokinetic/pharmacodynamic/disease progression model in NC/Nga mice for development of novel anti-atopic dermatitis drugs.
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ジャーナル |
Xenobiotica
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Abstract |
1. JHL45, a novel immune modulator against atopic dermatitis (AD), was synthesized from decursin isolated from Angelica gigas. The goal is to evaluate the lead compound using quantitative modeling approaches to novel anti-AD drug development. 2. We tested the anti-inflammatory effect of JHL45 by in vitro screening, characterized its in vitro pharmacokinetic (PK) properties. The dose-dependent efficacy of JHL45 was developed using a pharmacokinetics/pharmacodynamics/disease progression (PK/PD/DIS) model in NC/Nga mice. 3. JHL45 has drug-like properties and pharmacological effects when administered orally to treat atopic dermatitis. The developed PK/PD/DIS model described well the rapid metabolism of JHL45, double-peak phenomenon in the PK of decursinol and inhibition of IgE generation by compounds in NC/Nga mice. Also, a quantitative model was developed and used to elucidate the complex interactions between serum IgE concentration and atopic dermatitis symptoms. 4. Our findings indicate that JHL45 has good physicochemical properties and powerful pharmacological effects when administered orally for treatment of AD in rodents.
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巻・号 |
44(11)
|
ページ |
975-87
|
公開日 |
2014-11-1
|
DOI |
10.3109/00498254.2014.924058
|
PMID |
24874886
|
MeSH |
Acrylates
Angelica / chemistry
Animals
Anti-Inflammatory Agents / pharmacokinetics*
Benzopyrans / pharmacokinetics*
Butyrates / pharmacokinetics*
Caffeic Acids / pharmacokinetics
Cell Line
Chromans
Coumarins / pharmacokinetics
Cytochrome P-450 Enzyme System / drug effects
Dermatitis, Atopic / drug therapy*
Disease Models, Animal*
Humans
Immunoglobulin E / blood
Male
Mice
Microsomes, Liver / drug effects
Rats
Rats, Sprague-Dawley
|
IF |
1.902
|
引用数 |
4
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
TOXICOLOGY
|
リソース情報 |
ヒト・動物細胞 |
|