Final answer:
Anionic, hydrophobic drugs that bind to albumin can affect competition for protein binding sites, influencing the pharmacokinetics of drugs through altered availability, clearance, and efficacy. This underlies the importance of accounting for plasma protein binding in drug discovery and development, as it affects drug distribution and toxicity.
Step-by-step explanation:
Competition for Plasma Protein Binding Sites
In step #2 of pharmacokinetics, distribution, drugs that are known to affect competition for protein binding sites include many anionic, hydrophobic drugs that bind to albumin. Albumin is a common protein in the blood that multiple drugs may bind to. If two drugs are capable of binding to the same site on albumin, they may compete, which alters the pharmacokinetics of the drugs. This competition can influence the availability of drugs in the bloodstream, reduce clearance, and even impact drug efficacy due to altered drug doses.
Drug-drug interactions mediated by serum albumin can be problematic, as a drug that displaces another from albumin can increase the unbound concentration of the displaced drug, potentially causing increased effects or toxicity. Drugs with high plasma protein binding (PPB) also demonstrate reduced clearance from the body, thereby extending their pharmacokinetic half-life. These concepts underscore the importance of understanding PPB during the early stages of drug discovery and screening, often using techniques such as in vitro equilibrium dialysis and ultrafiltration.
Furthermore, the penetration of drugs into the brain can be influenced by their ability to cross the blood-brain barrier (BBB). Both physicochemical properties and biological factors like transporters and enzymes play roles in this process. Adjusting the properties of a compound, such as hydrogen bond characteristics and lipophilicity, can help to modulate its brain uptake and PPB.