title: Pharmacokinetic studies of linezolid and teicoplanin in the critically ill.
abstract: OBJECTIVE
  To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients.
  
  
  METHODS
  Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay.
  
  
  RESULTS
  A two-compartment model was required to characterize linezolid pharmacokinetics (n=28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 +/-0.016 L/h/kg (+/-s.e.m. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4 mg/L for 10.88 h (95% CI 10.09-11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% CI 57.2-127.7). Teicoplanin was best described by a two-compartment model (n=26). The clearance was 4.97+/-1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% CI 329.6-469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died.
  
  
  CONCLUSIONS
  Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level.
authors.affiliation: Bloomsbury Institute of Intensive Care Medicine, Department of Medicine, University College London, London, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Whitehouse
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Cepeda
authors.forename: Rob
authors.initials: R
authors.lastname: Shulman
authors.forename: Leon
authors.initials: L
authors.lastname: Aarons
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nalda-Molina
authors.forename: Caroline
authors.initials: C
authors.lastname: Tobin
authors.forename: Alasdair
authors.initials: A
authors.lastname: MacGowan
authors.forename: Steve
authors.initials: S
authors.lastname: Shaw
authors.forename: Chris
authors.initials: C
authors.lastname: Kibbler
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.forename: A Peter R
authors.initials: AP
authors.lastname: Wilson
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016638:Critical Illness; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D023303:Oxazolidinones / Q000493:pharmacokinetics* / Q000494:pharmacology; D011446:Prospective Studies; D017334:Teicoplanin / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000081:Acetamides; D023303:Oxazolidinones; D017334:Teicoplanin; D000069349:Linezolid