Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy

Roger, Claire, Wallis, Steven C., Muller, Laurent, Saissi, Gilbert, Lipman, Jeffrey, Lefrant, Jean-Yves and Roberts, Jason A. (2016) Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy. Antimicrobial Agents and Chemotherapy, 60 8: 4901-4909. doi:10.1128/AAC.00828-16

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ405859_OA.pdf Full text (open access) application/pdf 1.84MB 0

Author Roger, Claire
Wallis, Steven C.
Muller, Laurent
Saissi, Gilbert
Lipman, Jeffrey
Lefrant, Jean-Yves
Roberts, Jason A.
Title Influence of renal replacement modalities on amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 1098-6596
0066-4804
Publication date 2016-08-01
Sub-type Article (original research)
DOI 10.1128/AAC.00828-16
Open Access Status File (Publisher version)
Volume 60
Issue 8
Start page 4901
End page 4909
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2017
Language eng
Formatted abstract
The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CV-VHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h-1 for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h-1 for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.).
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 1 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 18 Sep 2016, 10:16:13 EST by System User on behalf of Learning and Research Services (UQ Library)