Which mechanism best explains why fentanyl's duration shortens after a single IV dose?

Which mechanism best explains why fentanyl's duration shortens after a single IV dose?

• A. Metabolism to active metabolite prolongs duration
• B. Renal excretion reduces duration
• C. Redistribution to inactive sites such as fat and skeletal muscle shortens duration
• D. Protein binding limits CNS entry

Answer: (C)

Fentanyl’s duration after a single IV dose is driven by redistribution from the brain to other tissues because it is highly lipophilic. After injection, it rapidly moves into well-perfused organs like the brain, producing a quick, potent effect. As it redistributes into less-perfused tissues such as fat and skeletal muscle, the brain concentration falls, and the opioid effects wear off even though plasma levels may remain relatively high. Metabolism to an active metabolite would tend to extend effects, not shorten them, and renal excretion plays only a minor role in determining duration. Protein binding can influence distribution, but the rapid loss of CNS effect is best explained by redistribution to inactive sites.

Fentanyl’s duration after a single IV dose is driven by redistribution from the brain to other tissues because it is highly lipophilic. After injection, it rapidly moves into well-perfused organs like the brain, producing a quick, potent effect. As it redistributes into less-perfused tissues such as fat and skeletal muscle, the brain concentration falls, and the opioid effects wear off even though plasma levels may remain relatively high. Metabolism to an active metabolite would tend to extend effects, not shorten them, and renal excretion plays only a minor role in determining duration. Protein binding can influence distribution, but the rapid loss of CNS effect is best explained by redistribution to inactive sites.