Cholesterol significantly affects drug interactions with membranes

Abstract

Abstract The pharmacokinetic profile of many drugs that target integral membrane proteins can be largely dictated by their interactions with the cell membrane at the molecular level. This includes a drugs' fast or slow passage through cell membranes en route to their target site of action and final compartmentalization in a membrane reservoir which contains the target protein. These interactions which can be distinctly different for each drug could help to explain both onset and duration of drug action. For many drugs, increasing amounts of cholesterol present in membranes, decreases the concentration of these drugs within the membrane buffer compartment. Membrane cholesterol can also affect the washout rate of drugs from membranes as well as the molecular location of drugs within the lipid bilayer of membranes. Some drugs are more or less tolerant to the presence of cholesterol in membranes, a property that is especially important in light of the finding that diet, disease and other factors can change cholesterol levels in membranes. These factors combine to make drugs within a given class more or less potent and can dictate how long they will remain within the therapeutic window of activity. This ‘membrane control’ mechanism of a given drug's clinical pharmacokinetics allows for optimal interaction between the drug and its final protein receptor target.