Pharmacokinetics of High-Dosage Thiopental Sodium in Patients with Cerebral Injuries

Pharmacokinetics of Thiopental Enantiomers during and following Prolonged High-dose Therapy

“…It is well-established that thiopental can show nonlinear (Michaelis-Menten or saturable) kinetics when administered in high doses for prolonged periods. [1][2][3][4][5][6][7][8] The progression from linear to nonlinear conditions coincides with increasing body (and thus hepatic mixed-function oxidase) burden of thiopental.…”

“…2,19 During nonlinear conditions, a constant amount of the body burden is eliminated per unit-time and the circulating concentrations are disproportional to dose. As a general rule, if the rate of administration of a substance leads to protracted concentrations greater than the Michaelis constant (k m ) then the resultant concentrations can become substantially greater than those predicted by linear pharmacokinetic models and the elimination t 1 2 after cessation of administration increases with decreasing body burden until it reaches its limiting value of linear conditions.…”

“…In this model, the product of V d and K el is equal to the total body clearance (TCl). 7,8 The nonlinear model is based on the V m , k m , and ratio of total dose to V d for a given T iv using the MichaelisMenten equation (2):…”

“…It is well-established that thiopental shows nonlinear Michaelis-Menten pharmacokinetics at high doses. [1][2][3][4][5][6][7][8] Commercially available thiopental, being a racemate (rac-thiopental), is used as an equimolar mixture of R-and S-thiopental enantiomers.ʈ The pharmacokinetics 9,10 and effects 11,12 of R-and S-thiopental differ quantitatively after anesthesia induction doses. However, it is not known whether the nonlinearity of high-dose thiopental pharmacokinetics is an artifact of data analysis because of two drugs being combined or whether the component enantiomers each undergo nonlinear pharmacokinetics.…”

Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus

“…We decided to study a wide range of anesthetic concentrations that had been reported in clinical settings. For all anesthetics, the lowest concentration was selected according to plasma levels described in the literature for patients with raised intracranial pressure treated by deep barbiturate sedation (12)(13)(14)(15). For propofol we chose plasma levels obtained during sedation of ICU patients and in patients with elevated intracranial pressure (16,17).…”