Thiopentone pharmacokinetics and electrocorticogram pattern in sheep

Thiopentone pharmacokinetics and electrocorticogram patterns were studied in a group of six sheep given thiopentone intravenously (20 mg/kg). Plasma concentrations were determined using a high-performance liquid chromatography method. A three-compartment open model was selected to describe the disposition kinetics of thiopentone. The drug had an apparent volume of distribution of 1005 +/- 196 ml/kg; body clearance was 3.5 +/- 0.8 ml/min-kg and the half-life, based on the slope of the terminal portion of the curve, was 196 +/- 64 min. From the electrocorticogram pattern, it seems likely that the highest concentrations in brain occurred between 47 and 217 sec after commencing administration and a brain penetration half-time of 26.5 +/- 2.87 sec was calculated. At the time of awakening (36.6 +/- 6.36 min) 24.1 +/- 6.3% of the dose was located in the central compartment, 12.6 +/- 8.2 was in the shallow peripheral compartment, 38.8 +/- 14.1 was in the deep peripheral compartment and 24.6 +/- 10.3 had been eliminated. Using simulated curves, it appeared that suppression of the shallow peripheral compartment (muscle) did not change the time of awakening; in contrast when elimination-rate constant was decreased, awakening was delayed. It was suggested that the relatively short duration of thiopentone anaesthesia in sheep should be attributed mainly to elimination of the drug by hepatic metabolism and uptake by body fat. This hypothesis, which differs from the widely accepted view that the duration of thiopentone anaesthesia is independent of the rate of hepatic metabolism, is discussed in terms of differences in regional blood flow between sheep and monogastric species.