کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2486939 1114398 2009 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ionization-specific analysis of human intestinal absorption
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Ionization-specific analysis of human intestinal absorption
چکیده انگلیسی
This study presents a mechanistic QSAR analysis of human intestinal absorption of drugs and drug-like compounds using a data set of 567 %HIA values. Experimental data represent passive diffusion across intestinal membranes, and are considered to be reasonably free of carrier-mediated transport or other unwanted effects. A nonlinear model was developed relating %HIA to physicochemical properties of drugs (lipophilicity, ionization, hydrogen bonding, and molecular size). The model describes ion-specific intestinal permeability of drugs by both transcellular and paracellular routes, and also accounts for unstirred water layer effects. The obtained model was validated on two external data sets consisting of in vivo human jejunal permeability coefficients (Peff) and absorption rate constants (Ka). Validation results demonstrate good predictive power of the model (RMSE = 0.35-0.45 log units for log Ka and log Peff). High prediction accuracy together with clear physicochemical interpretation (log P, pKa) makes this model particularly suitable for use in property-based drug design. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4039-4054, 2009
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 98, Issue 11, November 2009, Pages 4039-4054
نویسندگان
, , , , ,