Journal of Bioequivalence & Bioavailability

Enhancement of Elevated Pharmacokinetic Drug Plasma Protein Binding in a Drug Discovery Program

Edginton Blaner^* Department of Pharmacy, Oklahoma State University, Stillwater, USA
^*Correspondence: Edginton Blaner, Department of Pharmacy, Oklahoma State University, Stillwater, USA, Email:

Received: 01-Mar-2023, Manuscript No. JBB-23-21355; Editor assigned: 06-Mar-2023, Pre QC No. JBB-23-21355 (PQ); Reviewed: 20-Mar-2023, QC No. JBB-23-21355; Revised: 27-Mar-2023, Manuscript No. JBB-23-21355 (R); Published: 03-Apr-2023, DOI: 10.35248/0975-0851.23.15.509

Description

Plasma protein binding is a crucial concept in pharmacology, as it helps to explain how drugs are transported and distributed throughout the body. Essentially, plasma protein binding refers to the degree to which a drug molecule is bound to the proteins present in the plasma portion of the blood. This process affects the bioavailability of drugs, their distribution throughout the body, and their ability to reach their target tissues.

Firstly, it is important to understand the different types of proteins present in the plasma and their roles in drug binding. Albumin is the most abundant protein in the plasma, making up around 60% of the total protein content.

It is responsible for transporting a wide variety of molecules, including drugs, hormones, and fatty acids. Other plasma proteins, such as globulins and fibrinogen, have more specialized functions such as immune defense and blood clotting. However, albumin is the main protein involved in drug binding due to its high concentration and low affinity for specific drugs.

When a drug enters the bloodstream, it is quickly distributed throughout the body. However, not all of the drug molecules are free to move around but some of them are bound to plasma proteins, particularly albumin. This binding is reversible and depends on the concentration of free drug molecules in the plasma. The fraction of drug molecules that are bound to plasma proteins is referred to as the plasma protein binding fraction or the binding affinity. There are several factors that affect the extent of plasma protein binding, including the physicochemical properties of the drug molecule and the characteristics of the plasma proteins. For example, drugs that are highly lipophilic or have a high molecular weight tend to have a greater affinity for plasma proteins than those that are more hydrophilic or have a lower molecular weight. This is because lipophilic drugs can bind to hydrophobic pockets on the surface of albumin molecules, while larger molecules have a greater surface area for binding interactions. The binding affinity of a drug can also be influenced by the presence of other drugs in the bloodstream. Some drugs may compete with each other for binding sites on plasma proteins, leading to decreased binding affinity and increased free drug concentration. This can have important clinical implications, as it may affect the efficacy and toxicity of drugs that are co-administered. For example, the anticoagulant warfarin is highly bound to plasma proteins, and its binding affinity can be affected by the concurrent administration of other drugs such as Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). One of the main implications of plasma protein binding is its effect on the bioavailability of drugs. Bioavailability refers to the fraction of an administered dose of a drug that reaches the systemic circulation in an active form. If a drug is highly bound to plasma proteins, it will be less available to interact with its target tissues, as it will be unable to cross the blood-brain barrier or enter cells that do not have specific transporters for the drug. This can lead to reduced therapeutic efficacy and may necessitate higher doses or more frequent administration to achieve the desired effect.

Plasma protein binding can also affect the distribution of drugs throughout the body. Because bound drugs are less available to interact with tissues and organs, they tend to be distributed less widely than free drugs. This can lead to the accumulation of the drug in certain tissues, which may be beneficial or harmful depending on the drug and the tissue involved. For example, the antimalarial drug chloroquine is highly bound to plasma proteins and accumulates in the liver, which is one of the main sites of its action. The degree of plasma protein binding varies among different drugs, ranging from highly bound (>90%) to poorly bound (<10%). Highly protein-bound drugs, such as warfarin and phenytoin, are known to have a long half-life and require a longer time to reach a steady-state concentration. This is because the protein-bound drug acts as a reservoir, releasing the drug slowly over time, which helps to maintain a steady plasma concentration. In contrast, poorly protein-bound drugs, such as ethanol and salicylic acid, have a short half-life and rapidly distribute throughout the body, resulting in a lower plasma concentration. Additionally, changes in protein binding can also occur due to alterations in plasma protein concentrations, such as in liver disease or malnutrition. In liver disease, the synthesis of plasma proteins is impaired, leading to a decrease in plasma protein concentration and an increase in the unbound fraction of drugs. This can result in a higher free drug concentration, leading to increased toxicity or adverse effects. Malnutrition can also result in decreased plasma protein concentrations, leading to a similar effect.