Many drugs need to pass through one or more cell membranes to reach their site of action. A common feature of all cell membranes is a phospholipid bilayer, about 10 nm thick, arranged with the hydrophilic heads on the outside and the lipophilic chains facing inwards. This gives a sandwich effect, with two hydrophilic layers surrounding the central hydrophobic one. Spanning this bilayer or attached to the outer or inner leaflets are glycoproteins, which may act as ion channels, receptors, intermediate messengers (G-proteins) or enzymes. The cell membrane has been described as a ‘fluid mosaic’ as the positions of individual phosphoglycerides and glycoproteins are by no means fixed (Figure 1.1). An exception to this is a specialized membrane area such as the neuromuscular junction, where the array of post-synaptic receptors is found opposite a motor nerve ending.

The general cell membrane structure is modified in certain tissues to allow more specialized functions. Capillary endothelial cells have fenestrae, which are regions of the endothelial cell where the outer and inner membranes are fused together, with no intervening cytosol. These make the endothelium of the capillary relatively permeable; fluid in particular can pass rapidly through the cell by this route. In the case of the renal glomerular endothelium, gaps or clefts exist between cells to allow the passage of larger molecules as part of filtration. Tight junctions exist between endothelial cells of brain blood vessels, forming the blood–brain barrier (BBB), intestinal mucosa and renal tubules.