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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration
International Journal of Antimicrobial Agents, Volume 44, No. 2, Year 2014
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Description
This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V1), 11.8 L; volume of distribution of peripheral compartment (V2), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12 h (q12 h) for 69 mL/kg/h, 1000 mg q12 h for 100 mL/kg/h and 1500 mg q12 h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings. © 2014 Elsevier B.V. and the International Society of Chemotherapy.
Authors & Co-Authors
Lipman, Jeffrey
Australia, Brisbane
The University of Queensland
Roberts, Jason A.
Australia, Brisbane
The University of Queensland
Australia, Brisbane
Royal Brisbane and Women's Hospital
Statistics
Citations: 28
Authors: 2
Affiliations: 4
Identifiers
Doi:
10.1016/j.ijantimicag.2014.03.009
ISSN:
09248579
Research Areas
Cancer
Health System And Policy
Study Design
Cross Sectional Study
Cohort Study
Participants Gender
Male