Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: Data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study

Sinnollareddy, Mahipal G., Roberts, Jason A., Lipman, Jeffrey, Akova, Murat, Bassetti, Matteo, De Waele, Jan J., Kaukonen, Kirsi-Maija, Koulenti, Despoina, Martin, Claude, Montravers, Philippe, Rello, Jordi, Rhodes, Andrew, Starr, Therese, Wallis, Steven C. and Dimopoulos, George (2015) Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: Data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study. Critical Care, 19 33: 1-7. doi:10.1186/s13054-015-0758-3


Author Sinnollareddy, Mahipal G.
Roberts, Jason A.
Lipman, Jeffrey
Akova, Murat
Bassetti, Matteo
De Waele, Jan J.
Kaukonen, Kirsi-Maija
Koulenti, Despoina
Martin, Claude
Montravers, Philippe
Rello, Jordi
Rhodes, Andrew
Starr, Therese
Wallis, Steven C.
Dimopoulos, George
Title Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: Data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study
Journal name Critical Care   Check publisher's open access policy
ISSN 1466-609X
1364-8535
Publication date 2015-02-04
Sub-type Article (original research)
DOI 10.1186/s13054-015-0758-3
Open Access Status DOI
Volume 19
Issue 33
Start page 1
End page 7
Total pages 7
Place of publication London, England, U.K.
Publisher BioMed Central Ltd.
Collection year 2015
Language eng
Subject 2706 Critical Care and Intensive Care Medicine
Formatted abstract
Introduction
The objective of the study was to describe the pharmacokinetics (PK) of fluconazole, anidulafungin, and caspofungin in critically ill patients and to compare with previously published data. We also sought to determine whether contemporary fluconazole doses achieved PK/pharmacodynamic (PD; PK/PD) targets in this cohort of intensive care unit patients.

Methods
The Defining Antibiotic Levels in Intensive care unit patients (DALI) study was a prospective, multicenter point-prevalence PK study. Sixty-eight intensive care units across Europe participated. Inclusion criteria were met by critically ill patients administered fluconazole (n = 15), anidulafungin (n = 9), and caspofungin (n = 7). Three blood samples (peak, mid-dose, and trough) were collected for PK/PD analysis. PK analysis was performed by using a noncompartmental approach.

Results
The mean age, weight, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores of the included patients were 58 years, 84 kg, and 22, respectively. Fluconazole, caspofungin, and anidulafungin showed large interindividual variability in this study. In patients receiving fluconazole, 33% did not attain the PK/PD target, ratio of free drug area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration (fAUC0–24/MIC) ≥100. The fluconazole dose, described in milligrams per kilogram, was found to be significantly associated with achievement of fAUC0–24/MIC ≥100 (P = 0.0003).

Conclusions
Considerable interindividual variability was observed for fluconazole, anidulafungin, and caspofungin. A large proportion of the patients (33%) receiving fluconazole did not attain the PK/PD target, which might be related to inadequate dosing. For anidulafungin and caspofungin, dose optimization also appears necessary to minimize variability.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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