ABSTRACT
This chapter describes the distribution of fat-soluble drugs. Hydrophilic drugs are mainly partially ionised - weak acids or bases have different kinetics: they are slowly and only partially absorbed, they are not subject to significant first-pass metabolism in the liver, they do not cross the healthy blood-brain barrier, they are only slightly protein-bound or not protein-bound at all, and they are filtered unchanged by the kidney. Protein binding is only a problem when one drug, such as the heart drug verapamil, displaces another, such as digoxin, from its binding site, leading to a sudden release of free, unbound drug and possible toxicity. Arfarin is 99% bound to plasma proteins, and is displaced by a number of drugs. The drug industry can often modify hydrophilic and/or ionised drug molecules so as to render them partially lipophilic.
