NON-LINEAR DISPOSITION OF THIOPENTONE FOLLOWING LONG-TERM INFUSION

The pharmacokinetics of thiopentone administered at infusion rates ran ging 45-11.5 mg.kg(-1) .h(-1) for 50-130 h was studied in 6 patients w ith neurologic evidence of severe cerebral damage. Arterial plasma con centrations of thiopentone were measured during and after discontinuat ion of the infusion. The postinfusion plasma concentrations were fitte d to the one compartment Michaelis-Menten model. At the end of the inf usion, 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 o f the terminal phase was 5.5 +/- 3.9 h.