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.
ジャーナル Xenobiotica
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.
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