The most important reason for the more rapid onset and shorter duration of action of fentanyl compared with morphine is the difference in which of the following?
A. Volume of distribution
B. Hepatic clearance
C. Renal clearance
D. Lipid solubility
E. Protein binding
The answer is D. Fentanyl is more lipid soluble than morphine, so it passes across the blood-brain barrier more easily and has a more rapid onset of action. Fentanyl also has a larger volume of distribution (Vd), slower plasma clearance, and longer elimination half-life than morphine. However, the duration of action of fentanyl (when given in small bolus doses) is much shorter than that of morphine because fentanyl is rapidly redistributed from the brain to inactive tissue sites (e.g., lipid sites). In larger bolus doses or continuous infusions, these tissue sites can become saturated, and the pharmacologic action of fentanyl becomes considerably prolonged. This is known as context sensitive half life and why if the kid has been on a fentanyl infusion for a while, don't expect it to be gone an hour after you shut it off.
Anaesthesia UK:Pharmacology of Opioids II