| Title | Prediction of oral absorption in humans by experimental immobilized artificial membrane chromatography indices and physicochemical descriptors. | | Author(s) | Kotecha J, Shah S, Rathod I, Subbaiah G | | Institution | Department of Quality Assurance, L.M. College of Pharmacy, P.O. Box 4011, Navrangpura, Ahmedabad 380009, India; Bioanalytical Laboratory, Bio Evaluation Centre, Torrent Research Center, At Village Bhat, 382428 Gandhinagar, India. | | Source | Int J Pharm 2008 Apr 22. | | Abstract | The purpose of the present study was to examine the human oral absorption (HOA) predictability of the experimentally determined immobilized artificial membrane (IAM) chromatography capacity factor [Formula: see text] in conjunction with physicochemical descriptors. Transcellular permeation was modeled based on determination of [Formula: see text] considering pH partition hypothesis, and the independent variables were polar surface area (PSA) and molecular weight (MW). The correlation between [Formula: see text] determined at different pH and n-octanol/water partition coefficient (logP) and contribution of polarity (PSA) and size (MW) in the transcellular permeation model were the extension to the previous work. A data set of 37 compounds with partition coefficient values taken from the literature was employed to show importance of ionic interaction in oral absorption prediction. The highest [Formula: see text] value among screened pH 4.5, 5.5, 6.5 and 7.4 [Formula: see text] in conjunction with PSA predicted HOA with coefficient of determination (CD) of 0.9001 compare to [Formula: see text] alone with CD of 0.8454 after excluding bretylium from the set of 28 structurally diverse drugs for known reason. PSA helped to avoid over estimation of HOA for amiloride, famotidine and furosemide. The model was tested for its applicability in drug development program and found to predict oral absorption using physically meaningful and structurally related properties making them relatively straightforward for a medicinal chemist to interpret. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18524510 |
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