Interrelation between plasma protein binding,rate of injection and the anesthetic effect of thiopental

• 1 Following thiopental injection to rabbits in doses of 5 mg kg^?1 intravenously (i.v.) the sleeping time lasted longer after injection by bolus than after administration made more slowly over 30 or 60 s, respectively.
• 2 Peak concentration in the blood of the animals after bolus injection was about four times higher than after slow injection.
• 3 The determination of protein binding showed that the unbound fraction of thiopental at the high concentration following bolus injection is almost doubled compared with the unbound concentration following the slow injections. Therefore it is concluded that this contributes to an increased concentration of thiopental in the brain during the initial phase of distribution thus extending the sleeping time.
• 4 The results from experiments using a distribution model give additional evidence supporting this conception.