Pharmacokinetics III

Drug molecules move around the body in three ways (Table 1):

• Bulk flow transfer – this refers to the movement of large amounts of the drug in the bloodstream, a process that is unaffected by the chemical nature of the drug.


• Filtration – the carriage of drug molecules dissolved in a volume of fluid crossing through gaps in the endothelium. Glomerular filtration is the most obvious example of drugs being filtered in the body although drugs are also filtered across the endothelium in many other organs. The rate of filtration is dependent on the concentration of drug in the fluid and the the rate of fluid transfer. This, in turn, is related to the hydrostatic pressure gradient driving fluid across the endothelium.


• Diffusional transfer – this refers to movement of drugs, molecule by molecule, over short distances (usually across membranes) and is greatly influenced by their chemical nature. The rate of diffusion of drug molecules across hydrophobic diffusion barriers such as membranes is strongly influenced by lipid solubility, whereas the delivery of drug molecules to and from the membrane is influenced by water solubility. The diffusion of drug molecules across membranes and cell walls is driven by the presence of a concentration gradient between the two sides of the membrane.