PHARMACOKINETICS OF HIGH-DOSAGE THIOPENTAL SODIUM IN PATIENTS WITH CEREBRAL INJURIES - INFLUENTIAL FACTORS ON KINETIC-MODEL AND ON PARAMETER VARIABILITY

Drug monitoring was performed over the duration of long-term, high-dos age thiopental sodium therapy in 119 patients hospitalised for neurolo gical damage. Total doses of 437.9+/-183.5 mg/kg for females and 310.8 +/-124.9 mg/kg for males were given over 126.5+/-48.2 hours. For the w hole group, the mean steady state plasma thiopental sodium concentrati on was 21.5+/-10.3 mg/L and the corresponding clearance value (CLss) w as 2.25+/-0.93 ml/min/kg. For each patient, the plasma concentration-t ime curve was plotted over the full period of data collection, accordi ng to a one-compartment model with linear elimination (96 patients) or (nonlinear) Michaelis-Menten elimination (23 patients). Linear and no nlinear groups exhibited no difference in demographic characteristics or in thiopental sodium treatment, but the total dose was statisticall y lower in males than in females. In patients with first-order kinetic s, the apparent volume of distribution (Vd) averaged 3.12+/-1.76 L/kg and elimination half-life was 18.3+/-11.0 hours. In patients with nonl inear kinetics, mean parameter values were 3.23+/-2.18 L/kg for Vd, 63 +/-19% for saturation of the enzymatic system, 15.3+/-10.8 mg/L for th e Michaelis constant (Km) and 15.3+/-10.8 mg/L/h fur the theoretical m aximum rate of drug elimination (Vm). Only plasma concentrations at ce ssation of thiopental sodium treatment (C-stop) discriminated between linear and nonlinear models (19.0+/-10.6 and 27.2+/-15.7 mdL, respecti vely).