Final answer:
Drugs that bind strongly to plasma proteins, such as albumin, may have reduced clearance and increased plasma levels. This plasma protein binding can slow the drug's distribution and reduce its efficacy, particularly when targeting the central nervous system.
Step-by-step explanation:
Many anionic, hydrophobic drugs bind to albumin, which can significantly affect their pharmacokinetics, including drug clearance and plasma levels. Drug distribution to tissues may be slowed due to this binding, and the clearance reduced, leading to an increase in the plasma levels of the drug. Such increased plasma levels might mean that there's a higher amount of the drug in circulation, but not necessarily a corresponding increase in its therapeutic effect due to reduced tissue distribution.
In the bloodstream, plasma protein binding (PPB) is a crucial factor in determining how much of a drug is available in an unbound form to enter tissues and exert a pharmacological effect. Drugs with high PPB have a reduced clearance rate and longer pharmacokinetic half-life. PPB also affects the efficacy of drugs intended for the central nervous system (CNS) because it influences their ability to cross the blood-brain barrier (BBB). Modifications to drug structures, such as reducing hydrogen bond donors and overall lipophilicity, have been strategies to circumvent issues associated with PPB and facilitate CNS penetration.