What causes the clinical effect of Propofol to be short-lived?

The clinical effect of Propofol is primarily short-lived due to redistribution into tissues. After administration, Propofol enters systemic circulation and rapidly leaves the bloodstream, distributing into highly perfused tissues such as the brain. Initially, this results in a quick onset of anesthesia; however, as the drug moves into these tissues, its concentration in the blood decreases, leading to a rapid recovery from its effects.

While Propofol is metabolized by the liver, and clearance from the circulation can contribute to its short duration, the immediate reason for its short-lived clinical effect is more significantly related to the redistribution process. This process happens much faster than metabolism can influence the drug's effect. Hence, redistribution is the primary driver of the quick recovery seen after Propofol administration. The drug's low plasma protein binding contributes to its free fraction ready for distribution, but it is the redistribution that limits the duration of action.