Where drugs hide: tissue reservoirs
Some tissues don't just receive a drug — they hoard it. A drug reservoir is a tissue that takes up a drug in large amounts and releases it only slowly, acting as a depot. The classic reservoir is body fat. Highly lipophilic drugs dissolve into fat because of their fat solubility, and since fat is poorly perfused, the drug enters slowly and leaves slowly. Other reservoirs include muscle and certain proteins inside tissues that grip the drug — a form of tissue binding — and even bone, which can store certain metals and antibiotics for years.
When a drug is locked away in a reservoir, the process is sometimes called drug sequestration. The stored portion is not active and not being cleared — it just waits. This has two faces. On the good side, a reservoir can prolong a drug's action by feeding it back into the blood over time, lengthening the effective half-life. On the risky side, a fat reservoir can quietly fill up over repeated doses, leading to slow drug accumulation — and a hangover of drug effect long after dosing stops, especially in patients with a lot of body fat.
Redistribution: when 'wearing off' isn't elimination
Here is one of the most elegant ideas in distribution. Redistribution is the movement of a drug from a fast-filling tissue to a slow-filling one *after* the dose. It explains a puzzle: how can a single dose of an intravenous general anaesthetic put someone to sleep in seconds, yet have them wake within minutes — even though most of the drug is still in the body?
- A lipophilic anaesthetic is injected; the well-perfused brain (high perfusion) gets a flood of drug within seconds → patient asleep.
- Plasma levels then fall as the drug spreads to muscle and other tissues that filled more slowly.
- Because plasma now holds less drug, the brain releases its drug back into the blood to re-equilibrate.
- Brain concentration drops below the effect threshold → patient wakes, even though little drug has actually been eliminated.
Putting the whole track together
Step back and the whole track tells one story. A drug enters the blood, then its fate is decided by a competition for it: plasma proteins try to hold it (plasma protein binding), well-perfused organs claim it first (perfusion), barriers gate the brain and fetus, and reservoirs hoard it (reservoirs and sequestration). The single number that summarizes the net result — how widely the drug spread — is the volume of distribution. And the dynamics of drug moving between these spaces over time is redistribution. Master these and you can predict where a drug goes, how long it acts, and why a blood level alone can fool you.