title: Prediction of the permeability of drugs through study on quantitative structure-permeability relationship.
abstract: This study is to research the quantitative structure-permeability relationship of 20 drugs having similar structure. Permeability was determined by using the Caco-2 cell in vitro model. The apparent permeability coefficient (Papp) of each drug both of apical to basolateral side and basolateral to apical side was measured at the concentration corresponding to 0.1 times the highest dose strength of 250 mL dissolved buffer. In order to test the permeability system suitability, we measured the Papp of 19 model drugs out of 20 which presented in 'Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms based on the Biopharmaceutics Classification System' of FDA guidance. Also, we demonstrated the functional expression of efflux systems (e.g., p-gp) by bi-directional transport studies with rhodamine 123. Also, as a result of the study on quantitative structure-permeability relationship by using the partial least square method, it was possible to predict the permeability of drugs from their 3D structure. The quantitative structure-permeability relationship provided a cross-validated q2=0.789, a normal r2=0.998. Considering all of above results, analysis on this quantitative structure-permeability relationship appears to be a very useful tool to predict the permeability.
authors.affiliation: Division of Biopharmaceutics, Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, #231 Jinheungno, Eunpyung-Gu, Seoul, Republic of Korea.
authors.forename: Seo Jeong
authors.initials: SJ
authors.lastname: Jung
authors.forename: Sun Ok
authors.initials: SO
authors.lastname: Choi
authors.forename: So Young
authors.initials: SY
authors.lastname: Um
authors.forename: Joo Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Hae Young Park
authors.initials: HY
authors.lastname: Choo
authors.forename: Su Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Chung
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D003198:Computer Simulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D013223:Statistics as Topic
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000894:Anti-Inflammatory Agents, Non-Steroidal