(40) Plasma Protein Binding | Plasma Protein Binding of Drug | Pharmacology of ADME | English

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Pharmacokinetic- “What does BODY 1 do to the DRUG 2” we have simple interchanged the BODY and DRUG to make a definition. And as per the definition, our body responds to any drug by giving ADME effects.
1. A Stands for - Absorption
2. D stands for - Distribution
3. M stands for - Metabolism
4. E stands for- Elimination

Drug distribution refers to the movement of a drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the tissues. (See also Introduction to Administration and Kinetics of Drugs.)

When a drug is absorbed and enters the systemic circulation, it is naturally distributed throughout the fluid and tissues in the body. Drug distribution is a subject that is covered in a branch of pharmacology called pharmacokinetics.

The drug distribution is usually varied and depends on several factors such as (1) Blood perfusion (2) Tissue binding (since drug binding is linked to the lipid content) (3) Regional pH (4) Cell membrane permeability

Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse.The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse. Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.

A drug in blood exists in two forms: bound and unbound. Depending on a specific drug's affinity for plasma protein, a proportion of the drug may become bound to plasma proteins, with the remainder being unbound. If the protein binding is reversible, then a chemical equilibrium will exist between the bound and unbound states, such that:

Protein + drug ⇌ Protein-drug complex
Notably, it is the unbound fraction which exhibits pharmacologic effects. It is also the fraction that may be metabolized and/or excreted. For example, the "fraction bound" of the anticoagulant warfarin is 97%. This means that of the amount of warfarin in the blood, 97% is bound to plasma proteins. The remaining 3% (the fraction unbound) is the fraction that is actually active and may be excreted.

Protein binding can influence the drug's biological half-life. The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form. Since the unbound form is being metabolized and/or excreted from the body, the bound fraction will be released in order to maintain equilibrium. Since albumin is alkalotic, acidic and neutral drugs will primarily bind to albumin. If albumin becomes saturated, then these drugs will bind to lipoprotein. Basic drugs will bind to the acidic alpha-1 acid glycoprotein. This is significant because various medical conditions may affect the levels of albumin, alpha-1 acid glycoprotein, and lipoproteins.

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