Journal article
Water–Solvent Partition Coefficients and Δ Log P Values as Predictors for Blood–Brain Distribution; Application of the Akaike Information Criterion
Journal of pharmaceutical sciences, Vol.99(5), pp.2492-2501
05/2010
DOI: 10.1002/jps.22010
PMID: 19967782
Abstract
It is shown that log P values for water–alkane or water–cyclohexane partitions, and the corresponding Δ log P values when used as descriptors for blood–brain distribution, as log BB, yield equations with very poor correlation coefficients but very good standard deviations, S from 0.25 to 0.33 log units. Using quite large data sets, we have verified that similar S‐values apply to predictions of log BB. A suggested model, based on log P for water–dodecane and water–hexadecane partition coefficients, has 109 data points and a fitted S = 0.254 log 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 S = 0.287 log units. We can find no causal connection between these log P values and log BB in terms of correlation or in terms of chemical similarity, but conclude that the log P descriptor will yield excellent predictions of log BB provided that predictions are within the chemical space of the compounds used to set up the model. We also show that model based on log P(octanol) and an Abraham descriptor provides a simple and easy method of predicting log BB with an error of no more than 0.31 log units. We have used the Akaike information criterion to investigate the most economic models for log BB. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2492–2501, 2010
Details
- Title: Subtitle
- Water–Solvent Partition Coefficients and Δ Log P Values as Predictors for Blood–Brain Distribution; Application of the Akaike Information Criterion
- Creators
- Michael H Abraham - Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UKWilliam E Acree - Department of Chemistry, University of North Texas, 1155 Union Circle Drive #305070, Denton, Texas 76203‐5017Albert J Leo - BioByte Corp., 201 W. Fourth St., Claremont, California 91711David Hoekman - David Hoekman Consulting, Inc., 107 NW 82nd, Seattle, Washington 97117Joseph E Cavanaugh - University of Iowa, Biostatistics
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.99(5), pp.2492-2501
- DOI
- 10.1002/jps.22010
- PMID
- 19967782
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/2010
- Academic Unit
- Statistics and Actuarial Science; Biostatistics; Injury Prevention Research Center
- Record Identifier
- 9983985711602771
Metrics
11 Record Views