Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration
Author
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Escobar Oregón, Leslie Dominique
Author
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Andresen, Max
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Author
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Downey, Patricio
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Author
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Gai Hernández, María Nella
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Author
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Regueira, Tomás
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Author
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Bórquez, Tamara
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Author
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Lipman, Jeffrey
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Author
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Roberts, Jason A.
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Admission date
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2014-12-17T15:51:35Z
Available date
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2014-12-17T15:51:35Z
Publication date
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2014
Cita de ítem
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International Journal of Antimicrobial Agents 44 (2014) 163–167
en_US
Identifier
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dx.doi.org/10.1016/j.ijantimicag.2014.03.009
Identifier
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https://repositorio.uchile.cl/handle/2250/121913
General note
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Artículo de publicación ISI
en_US
Abstract
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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.
en_US
Patrocinador
dc.description.sponsorship
This work was supported by a postgraduate grantfrom the National Commission of Science and Technology (CON-ICYT) of Chile [grant AT2012 no. 24121225] to LE and by theFaculty of Medicine of Universidad Católica for interdepartmen-tal research (Departments of Intensive Medicine and Nephrology).JAR is funded by a Career Development Fellowship from theNational Health and Medical Research Council of Australia [NHMRCAPP1048652]. The Burns, Trauma and Critical Care Research Cen-tre (Brisbane, Australia) acknowledges its NHMRC project grantfunding [APP1044941].