The Role of Metabolism and Protein Binding in Thiopental Anesthesia

Abstract

The role of metabolism, relative to redistribution, in the termination of anesthesia was examined in patients receiving a single bolus i.v. injection of thiopental. It was determined if nonlinear protein binding occurs immediately after the bolus i.v. injection of thiopental, possibly enhancing its effect. Thiopental pharmacokinetics and protein binding were determined in 12 surgical patients with normal hepatic function. Plasma concentration over time data were used to quantitate the contribution of metabolism to the early decline of thiopental plasma concentrations after a single i.v. bolus administration. The fraction of thiopental loss from the central compartment due to metabolism was calculated to be 0.14 .+-. 0.06 (mean .+-. SD) at 1 min and 0.18 .+-. 0.04 at 15 min. Apparently, metabolism is far less important than distribution in the initial decline of blood and brain concentrations of thiopental and therefore termination of thiopental anesthetic effect. The protein binding of thiopental from 0.5 to 15 min was linear over a concentration range of 93 .+-. 60 .mu.g/ml to 6.9 .+-. 0.62 .mu.g/ml. Concentration-dependent or nonlinear protein binding of thiopental after a single i.v. bolus administration was not demonstrated and does not enhance thiopental anesthetic effect.