کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485918 | 1114370 | 2010 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Water-Solvent Partition Coefficients and ÎâLogâP Values as Predictors for Blood-Brain Distribution; Application of the Akaike Information Criterion
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
It is shown that logâP values for water-alkane or water-cyclohexane partitions, and the corresponding ÎâlogâP values when used as descriptors for blood-brain distribution, as logâBB, yield equations with very poor correlation coefficients but very good standard deviations, S from 0.25 to 0.33âlog units. Using quite large data sets, we have verified that similar Sâvalues apply to predictions of logâBB. A suggested model, based on logâP for water-dodecane and water-hexadecane partition coefficients, has 109 data points and a fitted Sâ=â0.254âlog units. It is essential to include in the model an indicator variable for volatile compounds, and an indicator variable for drugs that contain the carboxylic group. A similar equation based on water-chloroform partition coefficients has 83 data points and a fitted Sâ=â0.287âlog units. We can find no causal connection between these logâP values and logâBB in terms of correlation or in terms of chemical similarity, but conclude that the logâP descriptor will yield excellent predictions of logâBB provided that predictions are within the chemical space of the compounds used to set up the model. We also show that model based on logâP(octanol) and an Abraham descriptor provides a simple and easy method of predicting logâBB with an error of no more than 0.31âlog units. We have used the Akaike information criterion to investigate the most economic models for logâBB. © 2009 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2492-2501, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 5, May 2010, Pages 2492-2501
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 5, May 2010, Pages 2492-2501
نویسندگان
Michael H. Abraham, William E. Jr., Albert J. Leo, David Hoekman, Joseph E. Cavanaugh,