title: Development of a pharmacokinetic/pharmacodynamic/disease progression model in NC/Nga mice for development of novel anti-atopic dermatitis drugs.
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.
authors.affiliation: College of Pharmacy, Kyungsung University , Busan , South Korea .
authors.forename: In-Hwan
authors.initials: IH
authors.lastname: Baek
authors.forename: Byung-Yo
authors.initials: BY
authors.lastname: Lee
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Chae
authors.forename: Gyu Yong
authors.initials: GY
authors.lastname: Song
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Kwon
mesh_terms: D000179:Acrylates; D029969:Angelica / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D001578:Benzopyrans / Q000493:pharmacokinetics*; D002087:Butyrates / Q000493:pharmacokinetics*; D002109:Caffeic Acids / Q000493:pharmacokinetics; D002460:Cell Line; D002839:Chromans; D003374:Coumarins / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C540133:3-(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo-3,4-dihydro-2H,8H-pyrano(3,2-g)chromen-3-yl-ester; D000179:Acrylates; D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D002087:Butyrates; D002109:Caffeic Acids; D002839:Chromans; D003374:Coumarins; D007073:Immunoglobulin E; D003577:Cytochrome P-450 Enzyme System; C101278:decursin
keywords: Atopic dermatitis; disease progression model; drug development; pharmacodynamics; pharmacokinetics