title: Population pharmacokinetics of ceftazidime in burn patients.
abstract: OBJECTIVE
  The aim of this study was to characterize, via a population pharmacokinetic approach, the pharmacokinetics of ceftazidime in burn patients who were not in the acute post-injury phase.
  
  
  METHODS
  The development of the pharmacokinetic model was based on data from therapeutic drug monitoring (41 patients, 94 samples). The estimation of population pharmacokinetic parameters and the selection of covariates (age, gender, body weight, size of burn and creatinine plasma concentration) that could affect the pharmacokinetics were performed with a nonlinear mixed effect modelling method.
  
  
  RESULTS
  No relationship between covariates and the pharmacokinetic parameters was established with the exception of an inverse-linear relationship between creatinine plasma concentration and ceftazidime total clearance. The total clearance of ceftazidime was 2.72 l h-1[coefficient variation (CV) = 56.3%] and the distribution volume of the central compartment was 0.28 l kg-1 (CV = 13.2%) The transfer rate constants (k12, k 21) between the central and peripheral compartments were 0.06718 h-1 (CV = 87.2%) and 0.001823 h-1 (CV = 82.7%), respectively. From these parameters, the total ceftazidime volume of distribution (10.64 l kg-1) was calculated.
  
  
  CONCLUSIONS
  The population parameters were different from those obtained in a previous study performed in fewer patients and in the early period after burn injury. In our study, the lower ceftazidime clearance could be explained by the relative decrease in ceftazidime elimination in relation to the burn area, and the higher ceftazidime volume of distribution in the presence of interstitial oedema, which could act as a reservoir from which ceftazidime returns slowly to the circulation.
authors: Clinical Pharmacology Department, Hôtel Dieu Hospital, Nantes, France. eric.dailly@chu-nantes.fr
authors: Eric
authors: E
authors: Dailly
authors: Michel
authors: M
authors: Pannier
authors: Pascale
authors: P
authors: Jolliet
authors: Michel
authors: M
authors: Bourin
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D002056:Burns / Q000378:metabolism*; D002442:Ceftazidime / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime