The effect of pathophysiology on pharmacokinetics in the critically ill patient - concepts appraised by the example of antimicrobial agents

Blot, Stijn I., Pea, Federico and Lipman, Jeffrey (2014) The effect of pathophysiology on pharmacokinetics in the critically ill patient - concepts appraised by the example of antimicrobial agents. Advanced Drug Delivery Reviews, 77 3-11. doi:10.1016/j.addr.2014.07.006


Author Blot, Stijn I.
Pea, Federico
Lipman, Jeffrey
Title The effect of pathophysiology on pharmacokinetics in the critically ill patient - concepts appraised by the example of antimicrobial agents
Journal name Advanced Drug Delivery Reviews   Check publisher's open access policy
ISSN 0169-409X
1872-8294
Publication date 2014-11-01
Year available 2014
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.addr.2014.07.006
Open Access Status DOI
Volume 77
Start page 3
End page 11
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 3003 Pharmaceutical Science
2700 Medicine
Abstract Critically ill patients are at high risk for development of life-threatening infection leading to sepsis and multiple organ failure. Adequate antimicrobial therapy is pivotal for optimizing the chances of survival. However, efficient dosing is problematic because pathophysiological changes associated with critical illness impact on pharmacokinetics of mainly hydrophilic antimicrobials. Concentrations of hydrophilic antimicrobials may be increased because of decreased renal clearance due to acute kidney injury. Alternatively, antimicrobial concentrations may be decreased because of increased volume of distribution and augmented renal clearance provoked by systemic inflammatory response syndrome, capillary leak, decreased protein binding and administration of intravenous fluids and inotropes. Often multiple conditions that may influence pharmacokinetics are present at the same time thereby excessively complicating the prediction of adequate concentrations. In general, conditions leading to underdosing are predominant. Yet, since prediction of serum concentrations remains difficult, therapeutic drug monitoring for individual fine-tuning of antimicrobial therapy seems the way forward.
Keyword Antimicrobial agents
Pharmacokinetics
Pharmacodynamics
Intensive care unit
Sepsis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
School of Medicine Publications
 
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