Pharmacokinetics III

The vast majority of drugs cross membranes by simple diffusion (Fig 4). This process does not require energy or any specialised transport molecules. The drug molecules simply diffuse through the membrane from an area of high concentration to an area of lower concentration down the concentration gradient. They may also diffuse back if a sufficient concentration builds up but this is unlikely because the molecules are either bound at their pharmacological site of action, diffuse across further membranes or are destroyed. To gain access to the membrane the drug must be dissolved in the aqueous solution around it and not be bound to larger molecules.

The large membrane surface area means that the process of simple diffusion is not saturable, so that the rate of transfer will continue to rise with increasing drug concentration. Furthermore, the non-specific nature of the process means that it is not inhibited by other drugs or molecules.

The rate of transfer of drug molecules will depend on:

• the concentration gradient


• the molecule (lipid solubility, degree of ionisation, size)


• the membrane (thickness, chemical composition)

Simple diffusion also occurs in aqueous solution and this can sometimes be a mechanism of passing through membranes (Fig 5). Many membranes have aqueous pores to facilitate the transport of small molecules and these can also be used by drugs.