1. Blood Flow

Organs with high blood flow, such as the heart, liver, kidneys, and brain, receive drugs more rapidly than those with lower blood flow, like muscles, adipose tissue, and skin. This explains why some drugs have a quick onset of action in highly perfused organs.

2. Tissue Permeability

For a drug to reach its target tissue, it must be able to cross various biological membranes. The permeability of these membranes depends on the drug's physicochemical properties:

• Lipid Solubility: Highly lipid-soluble (lipophilic) drugs can easily diffuse across cell membranes, which are primarily composed of lipids. This allows them to readily enter tissues, including the brain (crossing the blood-brain barrier) and adipose tissue. Conversely, water-soluble (hydrophilic) drugs have difficulty crossing lipid membranes and often require specific transporters or channels.
• Molecular Size: Smaller molecules generally distribute more easily than larger ones.

3. Plasma Protein Binding

Many drugs bind reversibly to plasma proteins, primarily albumin and alpha-1 acid glycoprotein. Only the unbound, or free, fraction of the drug can cross capillary walls and cell membranes to reach its site of action or be eliminated. Drugs that are highly protein-bound have a lower volume of distribution and may have a prolonged duration of action as the bound drug acts as a reservoir.

4. Volume of Distribution (Vd)

The apparent volume of distribution (Vd)is a theoretical pharmacokinetic parameter that relates the amount of drug in the body to the concentration of drug in the blood or plasma. It reflects how extensively a drug is distributed into body tissues and fluids rather than remaining in the plasma. A high Vd indicates that a drug is widely distributed into tissues, while a low Vd suggests that the drug primarily remains in the bloodstream.

Understanding (Vd) is crucial for determining the loading dose of a drug, which is the initial higher dose given to achieve the desired therapeutic concentration quickly.

5. Tissue Binding

Beyond plasma proteins, drugs can also bind to components within tissues, such as proteins, lipids, or nucleic acids. This tissue binding can lead to drug accumulation in certain organs, potentially prolonging their action or contributing to toxicity. For example, highly lipophilic drugs tend to accumulate in adipose tissue, which can act as a long-term reservoir.