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

Stijn Blot UGent, Federico Pea and Jeffrey Lipman (2014) ADVANCED DRUG DELIVERY REVIEWS. 77. p.3-11
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (review)
publication status
published
subject
keyword
Pharmacokinetics, Antimicrobial agents, Pharmacodynamics, Intensive care unit, Sepsis, Organ failure, Acute kidney injury, Hepatic failure, RENAL REPLACEMENT THERAPY, INTENSIVE-CARE-UNIT, ACUTE KIDNEY INJURY, STAPHYLOCOCCUS-AUREUS BACTEREMIA, ORGAN BLOOD-FLOW, SEPTIC SHOCK, SEVERE SEPSIS, CONTINUOUS-INFUSION, ATTRIBUTABLE MORTALITY, NOSOCOMIAL INFECTION
journal title
ADVANCED DRUG DELIVERY REVIEWS
Adv. Drug Deliv. Rev.
volume
77
pages
3 - 11
Web of Science type
Review
Web of Science id
000347498200002
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
15.038 (2014)
JCR rank
4/255 (2014)
JCR quartile
1 (2014)
ISSN
0169-409X
DOI
10.1016/j.addr.2014.07.006
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
4239801
handle
http://hdl.handle.net/1854/LU-4239801
date created
2014-01-21 11:11:23
date last changed
2016-12-19 15:45:01
@article{4239801,
  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.},
  author       = {Blot, Stijn and Pea, Federico and Lipman, Jeffrey},
  issn         = {0169-409X},
  journal      = {ADVANCED DRUG DELIVERY REVIEWS},
  keyword      = {Pharmacokinetics,Antimicrobial agents,Pharmacodynamics,Intensive care unit,Sepsis,Organ failure,Acute kidney injury,Hepatic failure,RENAL REPLACEMENT THERAPY,INTENSIVE-CARE-UNIT,ACUTE KIDNEY INJURY,STAPHYLOCOCCUS-AUREUS BACTEREMIA,ORGAN BLOOD-FLOW,SEPTIC SHOCK,SEVERE SEPSIS,CONTINUOUS-INFUSION,ATTRIBUTABLE MORTALITY,NOSOCOMIAL INFECTION},
  language     = {eng},
  pages        = {3--11},
  title        = {The effect of pathophysiology on pharmacokinetics in the critically ill patient: concepts appraised by the example of antimicrobial agents},
  url          = {http://dx.doi.org/10.1016/j.addr.2014.07.006},
  volume       = {77},
  year         = {2014},
}

Chicago
Blot, Stijn, Federico Pea, and Jeffrey Lipman. 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.
APA
Blot, S., Pea, F., & Lipman, J. (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.
Vancouver
1.
Blot S, Pea F, Lipman J. The effect of pathophysiology on pharmacokinetics in the critically ill patient: concepts appraised by the example of antimicrobial agents. ADVANCED DRUG DELIVERY REVIEWS. 2014;77:3–11.
MLA
Blot, Stijn, Federico Pea, and Jeffrey Lipman. “The Effect of Pathophysiology on Pharmacokinetics in the Critically Ill Patient: Concepts Appraised by the Example of Antimicrobial Agents.” ADVANCED DRUG DELIVERY REVIEWS 77 (2014): 3–11. Print.