Drug-phospholipid interactions. 2. Predicting the sites of drug distribution using n-octanol/water and membrane/water...

The in vivo tissue distribution of seventeen drugs has been modeled by using estimated n-octanol/water and membrane/water distribution coefficients. In this study, the membrane affinities are estimated using the new technique of immobilized artificial membrane (IAM) column chromatography. delta (log D(n-octanol/water-membrane/water)), which measures a hypothetical equilibrium of the drug between of n-octanol and membrane phase, is a better model of in vivo tissue distribution, as measured by Adipose Tissue Storage Index (ASI), than either n-octanol/ water or membrane/water distribution coefficients alone. This demonstrates the importance of membrane distribution coefficients as a complementary descriptor of lipophilicity to n-octanol/water distribution coefficients, in modeling in vivo distribution of drugs. This rapid method for predicting in vivo distribution of drugs, based on n-octanol and membrane/water distribution coefficients, may be a useful tool to aid the selection of drugs with beneficial pharmacokinetic profiles.