title: Evaluation of chromatographic descriptors for the prediction of gastro-intestinal absorption of drugs.
abstract: The use of chromatographic descriptors in QSAR was evaluated. Therefore, retentions were measured on an immobilized artificial membrane system, 2 micellar liquid chromatography systems and 17 orthogonal or disimilar reversed-phase liquid chromatographic systems. It was investigated whether it was possible to model gastro-intestinal absorption as a function of chromatographic retentions applying two linear and one non-linear multivariate modeling technique. In a second step it was evaluated if models built with theoretical descriptors could be improved by adding the measured retention factors to the data set of descriptive variables. It was seen that gastro-intestinal absorption could be modelled in function of chromatographic retention using the non-linear modeling technique multivariate adaptive regression splines (MARS). The best models were obtained using a combination of theoretical and chromatographic descriptors with MARS as modeling technique.
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Deconinck
authors.forename: H
authors.initials: H
authors.lastname: Ates
authors.forename: N
authors.initials: N
authors.lastname: Callebaut
authors.forename: E
authors.initials: E
authors.lastname: Van Gyseghem
authors.forename: Y
authors.initials: Y
authors.lastname: Vander Heyden
mesh_terms: D000070:Acebutolol / Q000737:chemistry / Q000493:pharmacokinetics; D000465:Algorithms; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007408:Intestinal Absorption; D008962:Models, Theoretical; D015999:Multivariate Analysis; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D021281:Quantitative Structure-Activity Relationship; D012997:Solvents; D014700:Verapamil / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D000070:Acebutolol; D014700:Verapamil