Interaction of thiopental with esomeprazole in critically ill patients

Introduction Thiopental is a thiobarbiturate given in the case of brain injuries to reduce intracranial pressure and to manage cerebral ischemia. A pharmacokinetic model has been described previously in critically ill patients with a different therapeutic strategy. New treatment options prompted us to investigate if drug–drug interactions occur. A new model is proposed describing the influence of concomitant administration of esomeprazole on the distribution of thiopental. Method The study population comprised 52 critically ill patients (body weight 47.1–114 kg) aged 18–78 years who had been admitted into the critical care unit for treatment of intracranial hypertension. A total mean dose of 282.8 ± 172.7 mg/kg was given in 96 ± 72 h. Pharmacokinetic analysis was performed by using a nonlinear mixed-effect population model. Result A one-compartment open model with first-order elimination identified two covariates, namely, body weight on clearance and volume of distribution, and the administration of esomeprazole on volume of distribution. The mean values (% relative standard error) for total clearance (CL) and for central volume of distribution (V d ) in patients with and without concomitant esomeprazole were 5.3 L/h (9.2 %) and 256.1 (6.4 %) and 153.2 l (19.2 %), respectively. Conclusion Based on these results, we conclude that concomitant administration of esomeprazole increases the volume of distribution and the half-live of thiopental. This drug–drug interaction should be considered when a target concentration has to be reached.