Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration.
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 (V(1)), 11.8L; volume of distribution of peripheral compartment (V(2)), 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 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h 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.
Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, Santiago, Chile.
Leslie
L
Escobar
Department of Intensive Care Medicine, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago 8330024, Chile. Electronic address: andresen@med.puc.cl.
Max
M
Andresen
Department of Nephrology, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago, Chile.
Patricio
P
Downey
Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, Santiago, Chile.
Maria Nella
MN
Gai
Department of Intensive Care Medicine, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago 8330024, Chile.
Tomás
T
Regueira
Department of Nephrology, Hospital Clínico Universidad Católica de Chile, Marcoleta 347, Santiago, Chile.
Tamara
T
Bórquez
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia.
Jeffrey
J
Lipman
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Jason A
JA
Roberts
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D016638:Critical Illness; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D012772:Shock, Septic / Q000628:therapy*; D053719:Tandem Mass Spectrometry; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D014640:Vancomycin
Critically ill patient; Dose simulation; High-volume haemofiltration; Population pharmacokinetics; Vancomycin