Volume of Distribution

Perfusion

distribution of drugs around the body via blood or lymphatic tissue

Volume of Distribution

Theoretical measure which represents extent to which a drug is distributed throughout the body. Calculated as concentration = dose/volume.

Biological Barriers

Barriers that a drug must be able to cross to reach its target, including the gastrointestinal mucosa, blood brain barrier, and placenta.

Hydrophilic/Highly Polar Small Molecule Drugs

distribute into the extracellular fluid and have a relatively small volume of distribution

Highly Lipid Soluble Drugs

Distribute far more widely into tissues, especially fatty tissues. Large volume of distribution.

Factors Affecting Distribution

Molecular size, lipid solubility, ionisation, binding to plasma proteins, rate of blood flow, and drug chemistry.

Protein Binding

The extent to which a drug binds plasma proteins. Can distort volume of distribution value as only free drug concentration is considered

Membrane Permeability

Drug’s ability to cross cell membranes. Affected by tight junctions, drug size, lipophilicity and pKa value etc

Tissue Partitioning

Distribution of a drug between different tissues. Affected by tissue composition, drug ionisation and lipophilicity.

What is tissue binding affected by?

Factors such as albumin, lipoprotein, acidic phospholipid lysosomal binding, lipophilicity, and drug pKa.

One Compartment Model

drug is assumed to be immediately where it's meant to be, as the body is considered homogenous.

Two Compartment Model

considers the drug distribution in other body tissues

Drug Accumulation

Drugs accumulate in specific compartments of the body, leading to potential side effects or toxicity.

Fat Partitioning

Minor clinical issue due to poor perfusion, but can still lead to drug accumulation.

Free Drug Concentration

Concentration of unbound drug in systemic circulation. Determines active site drug concentration and therefore efficacy

Organs of Elimination

liver and kidney