title: Population pharmacokinetics of four β-lactams in critically ill septic patients comedicated with amikacin.
abstract: OBJECTIVE
  The study aimed to characterize the pharmacokinetics (PK) of four β-lactams (piperacillin, ceftazidime, cefepime, and meropenem) in patients comedicated with amikacin (AMK), and to confirm the predictive performance of AMK data, obtained from therapeutic drug monitoring (TDM), on these PK, using a population modeling approach.
  
  
  METHODS
  Serum samples were collected in 88 critically ill septic patients. For each β-lactam, the covariate model was optimized using renal function. Furthermore, predictive performance of AMK concentrations and PK parameters was assessed on β-lactam PK.
  
  
  RESULTS
  A two-compartment model with first-order elimination best fitted the β-lactam data. Results supported the superiority of AMK concentrations, over renal function and AMK PK parameters, to assess the β-lactam PK.
  
  
  CONCLUSIONS
  The study confirmed the significant link between the exposure to AMK and to β-lactams, and presented population models able to guide β-lactam dosage adjustments using renal biomarkers or TDM-related aminoglycoside data.
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Isabelle K
authors.initials: IK
authors.lastname: Delattre
authors.forename: Flora T
authors.initials: FT
authors.lastname: Musuamba
authors.forename: Philippe
authors.initials: P
authors.lastname: Jacqmin
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Taccone
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.forename: Roger K
authors.initials: RK
authors.lastname: Verbeeck
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000583:Amikacin / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000077723:Cefepime; D002442:Ceftazidime / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000493:pharmacokinetics; D016638:Critical Illness; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D010878:Piperacillin / Q000493:pharmacokinetics; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D013845:Thienamycins / Q000493:pharmacokinetics; D014018:Tissue Distribution; D016896:Treatment Outcome; D047090:beta-Lactams / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D013845:Thienamycins; D047090:beta-Lactams; D000077723:Cefepime; D000583:Amikacin; D002442:Ceftazidime; D000077731:Meropenem; D010878:Piperacillin