The effects of major burn related pathophysiological changes on the pharmacokinetics and pharmacodynamics of drug use: An appraisal utilizing antibiotics

Andrew A. Udy, Jason A. Roberts, Jeffrey Lipman, Stijn Blot

Research output: Contribution to journalArticleOtherpeer-review

19 Citations (Scopus)

Abstract

Patients suffering major burn injury represent a unique population of critically ill patients. Widespread skin and tissue damage causes release of systemic inflammatory mediators that promote endothelial leak, extravascular fluid shifts, and cardiovascular derangement. This phase is characterized by relative intra-vascular hypovolaemia and poor peripheral perfusion. Large volume intravenous fluid resuscitation is generally required. The patients' clinical course is then typically complicated by ongoing inflammation, protein catabolism, and marked haemodynamic perturbation. At all times, drug distribution, metabolism, and elimination are grossly distorted. For hydrophilic agents, changes in volume of distribution and clearance are marked, resulting in potentially sub-optimal drug exposure. In the case of antibiotics, this may then promote treatment failure, or the development of bacterial drug resistance. As such, empirical dose selection and pharmaceutical development must consider these features, with the application of strategies that attempt to counter the unique pharmacokinetic changes encountered in this setting.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalAdvanced Drug Delivery Reviews
Volume123
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Antibiotics
  • Augmented renal clearance
  • Bacterial resistance
  • Burn injury
  • Critical illness
  • Drug dosing
  • Systemic inflammation

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