Thiopentone has a shorter clinical duration of action (10–15 min) after a single bolus despite its long elimination half-life (11 hours). This is best explained by:
- A Rapid hepatic first-pass metabolism when cardiac output redistributes blood to the liver
- B Active transport of thiopentone out of brain parenchyma by P-glycoprotein efflux pumps
- C Redistribution from brain to muscle and fat as plasma concentrations fall ✓
- D Rapid renal excretion because thiopentone is not protein-bound in the ionised state
Explanation
After a single bolus, thiopentone rapidly reaches peak brain concentration causing unconsciousness. Over the next 10–15 minutes, the plasma concentration falls as the drug redistributes from well-perfused brain to the larger but less-perfused muscle compartment, and eventually to fat. This redistribution lowers brain concentration below the threshold for anaesthesia, producing awakening before significant hepatic metabolism has occurred. With repeated doses or infusions, however, muscle and fat become saturated, redistribution no longer terminates the effect, and prolonged unconsciousness ensues — the basis of context-sensitive half-time.
Reference: Morgan & Mikhail's Clinical Anesthesiology, 6th ed.
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Written and medically reviewed by the StethoPrep medical team.