Distribution: Tissue permeability of drugs, binding of drugs, Apparent, volume of drug distribution, Plasma and tissue protein binding of drugs, Factors affecting protein-drug binding. Kinetics of protein binding, Clinical significance of protein binding of drugs.

Drug disposition in the body depends greatly on how a drug moves from the bloodstream into different tissues and organs. Tissue permeability determines the extent to which a drug can cross biological membranes and enter tissues. Factors such as lipid solubility, molecular size, ionization, blood flow, and membrane characteristics influence drug penetration into tissues.

After entering the circulation, many drugs undergo binding to proteins present in plasma and tissues. This process is known as protein-drug binding. Drugs may bind reversibly to plasma proteins such as albumin and α₁-acid glycoprotein, as well as to proteins within tissues. Generally, only the unbound (free) drug is readily available for diffusion, pharmacological action, metabolism, and excretion, although protein-bound drug can act as a reservoir that releases free drug.

The extent of drug distribution is commonly described by the volume of distribution (Vd). It is an apparent volume that relates the amount of drug in the body to its plasma concentration. The apparent volume of distribution does not necessarily represent a real anatomical volume; rather, it indicates the extent to which a drug leaves the plasma and distributes into tissues.

Plasma protein binding depends on drug properties and protein characteristics, whereas tissue protein binding can cause accumulation of drugs in particular organs or tissues. Several factors, including drug concentration, protein concentration, affinity of binding sites, pH, age, disease, and the presence of other drugs, can affect protein-drug binding.

Protein-binding kinetics describes the relationship between free and bound drug and may involve linear or saturable binding. Understanding these processes is important because changes in protein binding can alter the free drug concentration and consequently affect drug response.

The clinical significance of protein binding includes its effects on drug distribution, duration of action, therapeutic response, drug interactions, toxicity, and elimination. Therefore, knowledge of tissue permeability, drug distribution, protein binding, and volume of distribution is essential for understanding the pharmacokinetic behaviour of drugs.

Dr Alok Bains

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