Transport of Drugs across Membranes

Abstract

In contrast to many compounds of physiological significance the penetration of drugs through membranes is, in general, passive, by diffusion or filtration. Most drugs are weak organic acids or bases, which in the unionized state are lipid soluble, but are hydrophilic when dissociated. In the undissociated state they can penetrate lipid membranes but not when present as ions. Hydrophilic compounds penetrate membranes only when pores are present or, when transported actively by special mechanisms. The permeation of drugs depends, accordingly, on their lipid solubility, pK_a and pH on the one hand and on the nature of the membrane on the other. When pH gradients exist across a lipid membrane, bases will concentrate on the more acid side and acids on themore alkaline side, i.e. in that space in which a larger proportion of the substance is dissociated and trapped as non-penetrating ion (Sehanker 1962). This type of diffusion has been called “non-ionic diffusion” by Milne et al. (1958).