Plasma and target-site subcutaneous tissue population pharmacokinetics and dosing simulations of cefazolin in post-trauma critically ill patients

Roberts, Jason A., Udy, Andrew A., Jarrett, Paul, Wallis, Steven C., Hope, William W., Sharma, Raman, Kirkpatrick, Carl M. J., Kruger, Peter S., Roberts, Michael S. and Lipman, Jeffrey (2014) Plasma and target-site subcutaneous tissue population pharmacokinetics and dosing simulations of cefazolin in post-trauma critically ill patients. Journal of Antimicrobial Chemotherapy, 70 5: 1495-1502. doi:10.1093/jac/dku564


Author Roberts, Jason A.
Udy, Andrew A.
Jarrett, Paul
Wallis, Steven C.
Hope, William W.
Sharma, Raman
Kirkpatrick, Carl M. J.
Kruger, Peter S.
Roberts, Michael S.
Lipman, Jeffrey
Title Plasma and target-site subcutaneous tissue population pharmacokinetics and dosing simulations of cefazolin in post-trauma critically ill patients
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2014-05-05
Sub-type Article (original research)
DOI 10.1093/jac/dku564
Volume 70
Issue 5
Start page 1495
End page 1502
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2016
Language eng
Formatted abstract
Objectives: The objective of this study was to describe the population pharmacokinetics of cefazolin in plasma and the interstitial fluid of subcutaneous tissue of post-trauma critically ill patients and provide clinically relevant dosing recommendations that result in optimal concentrations at the target site.

Patients and methods: This was a pharmacokinetic study in a tertiary referral ICU. We recruited 30 post-trauma critically ill adult patients and collected serial total and unbound plasma cefazolin concentrations. Interstitial fluid concentrations were determined using in vivo microdialysis. Population pharmacokinetic analysis and Monte Carlo simulations were undertaken with Pmetrics®. Fractional target attainment against an MIC distribution for Staphylococcus aureus isolates was calculated.

Results: The mean (SD) age, weight, APACHE II score and CLCR were 37.0 (14.1) years, 86.8 (22.7) kg, 16.9 (5.3) and 163 (44) mL/min, respectively. A three-compartment linear population pharmacokinetic model was most appropriate. Covariates included in the model were CLCR on drug clearance and serum albumin concentration and body weight on the volume of the central compartment. The fractional target attainment for a 1 g intravenous 8-hourly dose for a CLCR of 50 mL/min was 88%, whereas for a patient with a CLCR of 215 mL/min, a dose of 2 g 6-hourly achieved 84% fractional target attainment.

Conclusions: Clinicians should be mindful of the effects of elevated CLCR and serum albumin concentrations on dosing requirements for post-trauma critically ill patients.
Keyword PK
Pharmacodynamics
Antibiotics
Microdialysis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Medicine Publications
 
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