Relationship of octanol/water partition coefficient and molecular weight to cellular permeability and partitioning in...

We have used modified standard methods and derived new formulae to quantitate cell permeability (P), cell/media partitioning (λ), and intracellular sequestration or binding rate constants (m) for cultured S49 murine lymphoma cells in suspension. Using 15 standard compounds and anticancer drugs, we found quantitative relationships among log P, log PO (octanol/pH 7.4 buffer partition coefficient), and molecular weight (MW) such that logP = -4.5 + 0.56log (PO(MW)(-1/2)). A good correlation among P, λ, and MW was also determined with λ = 0.67 + 5890 gm(1/2) cm(-1) sec (P (MW)(1/2)). These studies show that there is a strong partitioning (λ) dependence to molecular weight and permeability that can be predicted even for known carrier-transported and biotransformable compounds. Furthermore, results of this study show that the slope of the plot of permeability and lipophilicity is not necessarily unity as has been postulated from the results of other studies.