Using water–solvent systems to estimate in vivo blood–tissue partition coefficients

Caitlin E. Derricott, Emily A. Knight, William E. Acree, Andrew SID Lang

Blood-tissue partition coefficients indicate how a chemical will distribute throughout the body and are an important part of any pharmacokinetic study. They can be used to assess potential toxicological effects from exposure to chemicals and the efficacy of potential novel drugs designed to target certain organs or the central nervous system. In vivo measurement of blood-tissue partition coefficients is often complicated, time-consuming, and relatively expensive, so developing in vitro systems that approximate in vivo ones is desirable. We have determined such systems for tissues such as brain, muscle, liver, lung, kidney, heart, skin, and fat. Several good (p < 0.05) blood-tissue partition coefficient models were developed using a single water-solvent system. These include blood-brain, blood-lung, blood-heart, blood-fat, blood-skin, water-skin, and skin permeation. Many of these partition coefficients have multiple water-solvent systems that can be used as models. Several solvents-methylcyclohexane, 1,9-decadiene, and 2,2,2-trifluoroethanol-were common to multiple models and thus a single measurement can be used to estimate multiple blood-tissue partition coefficients. A few blood-tissue systems require a combination of two water-solvent partition coefficient measurements to model well (p < 0.01), namely: blood-muscle: chloroform and dibutyl ether, blood-liver: N-methyl-2-piperidone and ethanol/water (60:40) volume, and blood-kidney: DMSO and ethanol/water (20:80) volume. In vivo blood-tissue partition coefficients can be easily estimated through water-solvent partition coefficient measurements.Graphical abstract:Predicted blood-brain barrier partition coefficients coloured by measured log BB value.