title: Pharmacokinetic modelling of cefotaxime and desacetylcefotaxime--a population study in 25 elderly patients.
abstract: OBJECTIVE
  To develop a pharmacostatistical model to simultaneously characterise the pharmacokinetics of cefotaxime and its main metabolite, desacetylcefotaxime, in elderly patients.
  
  
  METHODS
  Cefotaxime, 1 g, was infused three times daily to 25 elderly patients, 66-93 years old. Cefotaxime and desacetylcefotaxime plasma concentrations (289 and 304 samples, respectively), along with demographic and physiological characteristics, were analysed using a population approach.
  
  
  RESULTS
  Cefotaxime pharmacokinetics was best described by a two-compartment open model in which desacetylcefotaxime was produced from the central compartment. The final parameter estimates were derived from simultaneous fit of parent/metabolite data. Cefotaxime clearance, mean 5.5 l/h, was positively influenced by body weight and serum protein concentration and negatively influenced by serum creatinine and age. In contrast, desacetylcefotaxime elimination was only decreased by age. The mean terminal half-lives of cefotaxime and desacetylcefotaxime were 1.7 h and 2.6 h, respectively. The stability and predictive performance of the final population pharmacokinetic model was assessed using 200 bootstrap samples of the original data.
  
  
  CONCLUSIONS
  Cefotaxime and desacetylcefotaxime elimination decreased with increasing age above 60 years. This decreased elimination was related to individual characteristics that are typically related to renal function.
authors.affiliation: Laboratoire de Pharmacologie, Centre René Huguenin, 35 rue Dailly, 92210 Saint Cloud, France. s.urien@stcloud-huguenin.org
authors.forename: S
authors.initials: S
authors.lastname: Urien
authors.forename: N
authors.initials: N
authors.lastname: Laurent
authors.forename: J
authors.initials: J
authors.lastname: Barre
authors.forename: M
authors.initials: M
authors.lastname: Druguet
authors.forename: M
authors.initials: M
authors.lastname: Bouvier D'yvoire
authors.forename: P
authors.initials: P
authors.lastname: Maire
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects* / Q000502:physiology; D001798:Blood Proteins / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D015577:Geriatric Assessment / Q000379:methods / Q000706:statistics & numerical data; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007297:Inpatients; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D013997:Time Factors
chemical_list: D001798:Blood Proteins; C029281:desacetylcefotaxime; D002439:Cefotaxime