Abstract

Experiments in rats have shown that after rapid intravenous injection of a single dose of thiopental, the brain equilibrates immediately with a very high plasma level, which then falls rapidly as the drug distributes into total body water and tissue binding sites, including fat. Consequently, the brain thiopental falls rapidly from an anesthetic to a nonanesthetic concentration as the plasma level falls to its initial plateau within a few minutes. Pentobarbital equilibration on the other hand, is delayed for a few minutes. Consequently, the brain concentration rises to a plateau while the plasma level is falling, and no dose of pentobarbital can produce a rapidly falling brain level. These findings are sufficient to explain why thiopental is an ultra-short-acting anesthetic while pentobarbital is not. The high lipid solubility of thiopental (in contrast to pentobarbital) may well be responsible for the rapid equilibration with brain, and thus for the ultrashort duration of action. Because of its poor blood supply, depot fat takes up thiopental too slowly to be of great importance in the early events that terminate the anesthetic action of a single small dose of thiopental.