drug sequestration

Sometimes a drug gets caught in a corner of the body and cannot easily get back out — like a coin slipping behind the sofa cushions. Drug sequestration is the trapping of a drug within a particular tissue or compartment, holding it apart from the general circulation and delaying when it becomes available or eliminated.

Sequestration can happen by several routes: very strong tissue binding, accumulation inside cellular organelles, or pH trapping, where a drug becomes charged after crossing a membrane and can no longer diffuse back out. A classic example is ion trapping of weakly basic drugs (such as chloroquine or amphetamines) inside acidic compartments like lysosomes or, with aspirin, in acidic urine.

Because sequestered drug is withheld from the blood, it can prolong a drug's half-life and persistence, sometimes for weeks. This can be a problem in overdose, where drug hidden in tissue keeps re-supplying the blood, but it can also be exploited — for instance, manipulating urine pH to trap and speed elimination of a poison.