fat solubility

Fat solubility describes how readily a drug dissolves in oils and fats rather than in water. A fat-loving (lipid-soluble) drug mixes comfortably with the body's fatty tissues — and, like oil and water not mixing, fat-soluble drugs tend to seek out the fatty parts of the body and gather there.

Because adipose (fat) tissue makes up a large portion of the body, highly fat-soluble drugs can accumulate there as a long-term store. Fat is poorly perfused, so it fills slowly and empties slowly, meaning the drug can linger for a long time. This storage in fat is a major reason some lipophilic drugs have a very long half-life and a large volume of distribution.

Fat solubility is closely tied to lipophilicity and is essential for crossing lipid membranes, but storage in fat is a double-edged feature. It can prolong action and complicate dosing in obesity, and stored drug may be released slowly over time or unexpectedly when fat is mobilised during fasting or rapid weight loss.