PARTITION-COEFFICIENTS OF DRUGS IN BILAYER-LIPID MEMBRANES

The oil/water partition coefficient of drugs is widely accepted as a k ey parameter in drug design. The coefficients are usually determined u sing a bulk octanol phase to represent the lipid. The physiologically and pharmacologically relevant structure is, of course, the bilayer li pid membrane, but until now there has been no convenient means of meas uring the partition coefficients of small molecules into a single bila yer. This paper demonstrates that the partition coefficient may be cal culated 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 ult ra-thin structure such as a lipid bilayer.