Prediction of drug transport processes using simple parameters and PLS statistics. The use of ACD/logP and ACD/ChemSketch descriptors.
A method of modelling and predicting biopharmaceutical properties using simple theoretically computed molecular descriptors and multivariate statistics has been investigated for several data sets related to solubility, IAM chromatography, permeability across Caco-2 cell monolayers, human intestinal perfusion, brain-blood partitioning, and P-glycoprotein ATPase activity. The molecular descriptors (e.g. molar refractivity, molar volume, index of refraction, surface tension and density) and logP were computed with ACD/ChemSketch and ACD/logP, respectively. Good statistical models were derived that permit simple computational prediction of biopharmaceutical properties. All final models derived had R(2) values ranging from 0.73 to 0.95 and Q(2) values ranging from 0.69 to 0.86. The RMSEP values for the external test sets ranged from 0.24 to 0.85 (log scale).
Osterberg
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AstraZeneca R&D Södertälje, SE-151 85, Södertälje, Sweden. thomas.osterberg@eu.pnu.com
Norinder
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000251:Adenosine Triphosphatases / Q000096:biosynthesis; D000704:Analysis of Variance; D001185:Artificial Intelligence; D001812:Blood-Brain Barrier; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D020650:Combinatorial Chemistry Techniques / Q000706:statistics & numerical data*; D017076:Computer-Aided Design / Q000706:statistics & numerical data*; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D008567:Membranes, Artificial; D012995:Solubility
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008567:Membranes, Artificial; D000251:Adenosine Triphosphatases