Pharmacokinetic evaluation of linezolid in patients with major thermal injuries

J Antimicrob Chemother. 2009 Mar;63(3):553-9. doi: 10.1093/jac/dkn541. Epub 2009 Jan 18.

Abstract

Aims: To evaluate the pharmacokinetics of linezolid following its administration in patients with major thermal injuries and in a group of healthy volunteers.

Methods: In an open-label, multicentre design with two parallel groups, a group of patients with major thermal injuries (>20% body area) and a group of age-, sex- and weight-matched healthy volunteers, subjects received a single 600 mg intravenous dose of linezolid. Serial blood and urine collections were made and the concentrations of linezolid in these samples were determined by HPLC. Non-compartmental analyses were used to describe the pharmacokinetic disposition of linezolid.

Results: C(max) concentrations and the volume of distribution at steady state (V(ss)) were not statistically different (P > 0.05) between the two groups of subjects. In contrast, values describing clearance [elimination rate constant (k(el)), t(1/2) and mean residence time (MRT)] were significantly different (P < 0.05) in patients with thermal injuries compared with volunteers, which lead to an approximate reduction by half in AUC(0-infinity) from 98.1 mg.h/L (volunteers) to 42.5 mg.h/L (patients). Although renal clearance was similar in the two groups (24.7 +/- 23 versus 30.6 +/- 14.3 mL/min; P = 0.156), non-renal clearance was substantially increased (323 +/- 191 versus 80.4 +/- 27.5 mL/min) in the patients with thermal injuries, though this difference did not achieve statistical significance (P = 0.063).

Conclusions: The pharmacokinetics of linezolid are altered in patients with major thermal injuries, mainly as a result of increased non-renal clearance. These changes are of sufficient magnitude that linezolid concentrations may be sub-therapeutic in some patients and we suggest that the dosage interval may need to be decreased in this patient population.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage
  • Acetamides / pharmacokinetics*
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Burns*
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Infusions, Intravenous
  • Linezolid
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Oxazolidinones / administration & dosage
  • Oxazolidinones / pharmacokinetics*
  • Plasma / chemistry*
  • Time Factors
  • Urine / chemistry*
  • Young Adult

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Oxazolidinones
  • Linezolid