Learning Objective

Explain the concept of drug redistribution, its impact on duration of action, and the clinical significance of active metabolites in pharmacokinetics.

Redistribution

Redistribution is the movement of lipid-soluble drugs from highly perfused tissues (e.g., brain, heart, liver) into less perfused tissues such as fat and muscle, before elimination.

Impact on CNS drugs:

• The duration of action of an initial dose often depends more on redistribution than on the drug’s half-life.
• Second dose effect: After redistribution, fat tissues already contain some drug; the blood-to-fat gradient is reduced, slowing redistribution and prolonging the duration of action.

Clinical Correlate:

• Active metabolites can contribute to prolonged drug effects.

Example: Diazepam is metabolized to nordiazepam, which retains sedative-hypnotic activity and has a longer duration of action.

Activity