Methohexital has a shorter elimination half-time than thiopental because methohexital?

Methohexital has a shorter elimination half-time than thiopental because methohexital?

• A. Is more lipid soluble
• B. Is more ionized in blood
• C. Has greater protein binding
• D. Has greater hepatic extraction

Answer: (D)

Elimination half-time reflects how quickly the drug is cleared, especially by the liver for these anesthetic barbiturates. When the liver extracts a larger fraction of the drug per pass (higher hepatic extraction), hepatic clearance increases. Since clearance rises while the volume of distribution is similar, the half-life becomes shorter. Methohexital is cleared more rapidly by hepatic metabolism than thiopental because it has greater hepatic extraction, so its elimination half-time is shorter. Lipid solubility mainly drives how fast the drug enters the brain and tissues (onset and distribution), not how quickly it is cleared. Ionization and protein binding influence distribution and free fraction, but they don’t explain the accelerated hepatic clearance that shortens the half-life.

Elimination half-time reflects how quickly the drug is cleared, especially by the liver for these anesthetic barbiturates. When the liver extracts a larger fraction of the drug per pass (higher hepatic extraction), hepatic clearance increases. Since clearance rises while the volume of distribution is similar, the half-life becomes shorter. Methohexital is cleared more rapidly by hepatic metabolism than thiopental because it has greater hepatic extraction, so its elimination half-time is shorter. Lipid solubility mainly drives how fast the drug enters the brain and tissues (onset and distribution), not how quickly it is cleared. Ionization and protein binding influence distribution and free fraction, but they don’t explain the accelerated hepatic clearance that shortens the half-life.