title: Interaction of thiopental with esomeprazole in critically ill patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 (Vd) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de Pharmacologie Médicale et Clinique APHM, Aix Marseille Université, Marseille, France. marsot.amelie@neuf.fr
authors.forename: Amélie
authors.initials: A
authors.lastname: Marsot
authors.forename: Françoise
authors.initials: F
authors.lastname: Goirand
authors.forename: Nadine
authors.initials: N
authors.lastname: Milési
authors.forename: Monique
authors.initials: M
authors.lastname: Dumas
authors.forename: Audrey
authors.initials: A
authors.lastname: Boulamery
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016638:Critical Illness; D004347:Drug Interactions; D064098:Esomeprazole / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D013874:Thiopental / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D006993:Hypnotics and Sedatives; D054328:Proton Pump Inhibitors; D013874:Thiopental; D064098:Esomeprazole