Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration

Sinnollareddy, Mahipal G., Roberts, Michael S., Lipman, Jeffrey, Robertson, Thomas A., Peake, Sandra L. and Roberts, Jason A. (2015) Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration. International Journal of Antimicrobial Agents, 45 2: 192-195. doi:10.1016/j.ijantimicag.2014.08.013

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Author Sinnollareddy, Mahipal G.
Roberts, Michael S.
Lipman, Jeffrey
Robertson, Thomas A.
Peake, Sandra L.
Roberts, Jason A.
Title Pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 0924-8579
1872-7913
Publication date 2015-02
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2014.08.013
Volume 45
Issue 2
Start page 192
End page 195
Total pages 4
Place of publication Amsterdam, The Netherlands
Publisher Elsevier
Collection year 2015
Language eng
Formatted abstract
Fluconazole is a widely used antifungal agent in critically ill patients. It is predominantly (60–80%) excreted unchanged in urine. Sustained low-efficiency diafiltration (SLED-f) is increasingly being utilised in critically ill patients because of its practical advantages over continuous renal replacement therapy. To date, the effect of SLED-f on fluconazole pharmacokinetics and dosing has not been studied. The objective of this study was to describe the pharmacokinetics of fluconazole in critically ill patients with acute kidney injury receiving SLED-f and to compare this with other forms of renal replacement therapy. Serial blood samples were collected at pre- and post-filter ports within the SLED-f circuit during SLED-f and from an arterial catheter before and after SLED-f from three patients during one session. Fluconazole concentrations were measured using a validated chromatography method. Median clearance (CL) and 24-h area under the concentration–time curve (AUC0–24) were 2.1 L/h and 152 mg·h/L, respectively, whilst receiving SLED-f. Moreover, 72% of fluconazole was cleared by a single SLED-f session (6 h) compared with previous reports of 33–38% clearance by a 4-h intermittent haemodialysis session. CL and AUC0–24 were comparable with previous observations in a pre-dilution mode of continuous venovenous haemodiafiltration. The observed rebound concentration of fluconazole post SLED-f was <2%. Although a definitive dosing recommendation is not possible due to the small patient number, it is clear that doses >200 mg daily are likely to be required to achieve the PK/PD target for common pathogens because of significant fluconazole clearance by SLED-f.
Keyword Pharmacokinetics
Fluconazole
Renal replacement therapy
Sustained low efficiency diafiltration
Extended daily diafiltration
Critically ill patients
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 14 Oct 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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