DRUG-PHOSPHOLIPID INTERACTIONS .2. PREDICTING THE SITES OF DRUG DISTRIBUTION USING N-OCTANOL WATER AND MEMBRANE/WATER DISTRIBUTION COEFFICIENTS/

The in vivo tissue distribution of seventeen drugs has been modeled by using estimated n-octanol/water and membrane/water distribution coeff icients. In this study, the membrane affinities are estimated using th e new technique of immobilized artificial membrane (IAM) column chroma tography. Delta(log D(n-ocatnol/water-membrane/water)), which measures a hypothetical equilibrium of the drug between of n-octanol and membr ane phase, is a better model of in vivo tissue distribution, as measur ed by Adipose Tissue Storage Index (ASI), than either n-octanol/water water or membrane/water distribution coefficients alone. This demonstr ates the importance of membrane distribution coefficients as a complem entary descriptor of lipophilicity to n-octanol/water distribution coe fficients, in modeling in vivo distribution of drugs. This rapid metho d 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.