Analysis of Algorithms Predicting Blood: Air and Tissue: Blood Partition Coefficient from Solvent Partition Coefficients for Use in Complex Mixture Physiological Based Pharmacokinetic/Pharmacodynamic Modeling
Abstract
Algorithms predicting tissue and blood partition coefficients (PCs) from solvent properties (octanol:water, saline or water:air, oil:air coefficients) were compared to assess their usefulness for a petroleum mixtures physiologically based pharmacokinetic/pharmacodynamic model. Measured blood:air and tissue:blood PCs were sought from literature resources for 14 JP-8 components. PCs, mainly from vial equilibration experiments, were separated by species (rat and human) and averaged by tissue and chemical. Average experimental PCs were then compared with predicted PCs calculated using algorithms from nine published sources. The algorithms chosen use solvent PCs due to the relative accessibility of these parameters. Tissue:blood PCs were calculated from ratios of predicted tissue:air and experimental blood:air values (PCEB). Calculated PCs were evaluated using percent error compared to the experimental value. Of the 231 calculated values, 29% performed within +/- 20% of the experimental PC values. Algorithms were divided into three main types. Empirical equations (derived from linear regression of experimental PC data), physiologically based equations (based on water and lipid components of a tissue type), and hybrid equations (physiological parameters and empirical factors combined) each performed equally well. PCEs values were compared with tissue:blood PCs calculated from ratios of predicted tissue:air and predicted blood:air values (PC(sub pb). Overall, 68% of PCER values had smaller absolute percent errors than PC(sub pb) values. Physiological equations should not be used to calculate PC(sub pb) values as 100% of these PCps values had higher absolute percent errors than corresponding PC(sub eb) values. If calculated PC values must be used in models, a comparison of experimental and predicted PCs for chemically similar compounds is advisable, so one understands the expected error level in calculated values.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA434945
Entities
People
- David R. Mattie
- G. A. Burton
- Peter J. Robinson
- Teresa R Sterner