Non linear disposition of thiopentone following long-term infusion

The pharmacokinetics of thiopentone administered at infusion rates ranging 4.5-11.5 mg.kg-1.h-1 for 50-130 h was studied in 6 patients with neurologic evidence of severe cerebral damage. Arterial plasma concentrations of thiopentone were measured during and after discontinuation of the infusion. The postinfusion plasma concentrations were fitted to the one compartment Michaelis-Menten model. At the end of the infusion, the level of saturation of the enzymatic systems ranged 67.0-95.7%. Vm was on average 0.93 +/- 0.57 mg.l-1.h-1. The mean plasma clearance was 2.0 +/- 1.4 ml.min-1.kg-1. The apparent half-life of the terminal phase was 5.5 +/- 3.9 h.