The pharmacokinetics of thiopentone

The pharmacokinetics of thiopentone was studied in six mongrel dogs using a high-performance liquid chromatographic method for measurement of the drug in the plasma. An intravenous bolus dose (20 mg/kg) of 2.5% thiopentone sodium solution was injected into the cephalic vein. While the two- and three-compartment models were used in the analysis of the experimental data, the disposition curve was adequately described by a biexponential equation. Plasma protein binding of thiopentone was determined in vitro using the equilibrium dialysis technique. The drug was bound to a moderately high extent (73.8 +/- 4.1%). The half-time of the initial phase, which comprises distribution/redistribution, was 14.9 +/- 3.3 mins. The apparent volume of distribution was quite high for an organic acid (843 +/- 194 ml/kg). This may be attributed to the high lipid solubility of the thiobarbiturate. The half-life was 6.99 +/- 2.18 h and a body clearance value of 1.51 +/- 0.60 ml/kg-min was obtained. It can be concluded from this study that the half-time of the distribution/redistribution phase approximates the duration of anaesthetic effect. Consequently, physiological conditions and disease states which influence distribution/redistribution rather than those affecting hepatic biotransformation of the drug are likely to affect anaesthesia.