Partition coefficients of drugs in bilayer lipid membranes.

The oil/water partition coefficient of drugs is widely accepted as a key parameter in drug design. The coefficients are usually determined using a bulk octanol phase to represent the lipid. The physiologically and pharmacologically relevant structure is, of course, the bilayer lipid membrane, but until now there has been no convenient means of measuring the partition coefficients of small molecules into a single bilayer. This paper demonstrates that the partition coefficient may be calculated from the change in membrane refractive index which occurs when a drug molecule partitions into the membrane. The refractive index is determined by an integrated-optics technique ideally suited to an ultra-thin structure such as a lipid bilayer.