title: Profiling and trend analysis of food effects on oral drug absorption considering micelle interaction and solubilization by bile micelles.
abstract: Correlation analysis between food effects on oral drug absorption (food effect) and physicochemical properties is important for efficient drug discovery and contributes to drug design. This study focused on micelle binding and solubilization considering bile micelles in the intestinal fluid. Profiling using about 40 launched drugs demonstrated that those in a high solubilization area (area 1) tended to have a positive food effect, and that drugs exhibiting negative/no food effect tended to coexist in a no/low solubilization area (area 2). In area 1, the solubilization effect by bile micelles was demonstrated quantitatively as an important factor that indicates a positive food effect. In area 2, the relative and quantitative relationships among the membrane permeation rate, dissolution rate, micelle binding and food effect could be clarified by simulation. The improvement of membrane permeability and the suppression of micelle binding are considered to be required to avoid a negative food effect. In conclusion, important factors contributing to the food effect were clarified relatively and quantitatively. Data generated from this profiling may be beneficial to find a solution for negative food effects. Furthermore, this risk assessment of food effects is considered to be a useful tool in rational drug design for drug discovery.
authors.affiliation: Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan. kawai.yukinori.f5@daiichisankyo.co.jp
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kawai
authors.forename: Yoshimine
authors.initials: Y
authors.lastname: Fujii
authors.forename: Fumiko
authors.initials: F
authors.lastname: Tabata
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Metsugi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kameda
authors.forename: Katsuya
authors.initials: K
authors.lastname: Akimoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D005502:Food; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008823:Micelles; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D008823:Micelles; D004364:Pharmaceutical Preparations