Prediction of drug tissue to plasma concentration ratios using a measured volume of distribution in combination with lipophilicity

One of the drug specific parameters needed in physiologically based pharmacokinetic (PBPK) models is the tissue to plasma drug concentration ratios (K-p values). The aim of this study was to develop an empirical method for predicting K-p values using a preclinically determined in vivo volume of distribution, in combination with descriptors for drug lipophilicity. Pharmacokinetic data in laboratory animals for a wide range of drug compounds were collected. Obtained correlations between K-p values for muscle and other tissues, in a training set of 49 compounds, were used to predict K-p values for a test set of 22 compounds, based on their volume of distribution and lipophilicity. Predicted K-p values agreed well with experimentally determined values (n = 118), especially for noneliminating tissues (r(2) =0.81) with 72% and 87% being within a factor +/-2 and +/-3, respectively. In conclusion, we present an empirical method based on a measured volume of distribution and a drug lipophilicity descriptor, which can be used to predict tissue K-p values with reasonable accuracy. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.