lipophilicity

Cell membranes are made of fat, so a drug's friendliness toward fat decides how easily it can slip through them. Lipophilicity is a drug's tendency to dissolve in fats and oils rather than water — its 'love of lipid' — and it is a master variable controlling membrane crossing, tissue penetration and accumulation.

Lipophilicity is commonly quantified by the partition coefficient (logP), measuring how a drug distributes between oil and water. Lipophilic drugs cross membranes readily by passive diffusion, so they tend to be well absorbed orally, penetrate the brain, and reach a wide range of tissues. They also accumulate in fatty tissue and bind more to lipid-rich cell components.

But more is not always better. Excessive lipophilicity can mean poor water solubility, sticky non-specific binding, accumulation in fat (prolonging half-life), and a heavier reliance on hepatic metabolism for elimination. Drug design therefore aims for a balanced, 'just right' lipophilicity rather than the maximum.