Population Pharmacokinetics (PK) of Vancomycin (VAN) in Neonates on Extra-Corporeal Life Support (ECLS)

Chad A. Knoderer; Kristen R. Nichols; Jeffrey Cies; Wayne Moore; Dominick Carella; Jason Parker; Paul Shea; Arun Chopra

Population Pharmacokinetics (PK) of Vancomycin (VAN) in Neonates on Extra-Corporeal Life Support (ECLS)

Chad A. Knoderer
, Kristen R. Nichols
, Jeffrey Cies
, Wayne Moore
, Dominick Carella
, Jason Parker
, Paul Shea
, Arun Chopra

Butler University

Research output: Contribution to conference › Presentation

Abstract

   Introduction:  VAN remains first line therapy for the treatment of life-threatening infections caused by methicillin resistant Staphylococcus aureus (MRSA) and ampicillin resistant Enterococci. Current evidence suggests that VAN trough levels of 15-20 mg/L or an AUC:MIC ratio of 400:1 are needed to maximize outcomes. Many factors can affect VAN PK in the pediatric ICU including sepsis and ECLS. Currently, no VAN PK data exists for children on ECLS with the current ECLS equipment. The purpose of this study was to describe VAN PK in children with a contemporary ECLS operation, including the Quadrox oxygenator
   Methods:  During the ECLS run, routine blood samples were collected from 14 neonates who received VAN for prophylaxis or empiric therapy. VAN concentrations were measured by fluorescent polarization and the population PK was determined using PMetrics. Multiple compartmental and covariate models were explored to determine the best fit of the data.
   Results:  13 neonates with a median gestational age of 36 weeks accounted for 16 VAN treatment courses. Each course contributed a median of 8 VAN levels (3-27) to the model. A 2 compartment model with weight as a covariate fit the VAN concentration data the best. Mean (SD) population estimates for clearance (CL), volume of the central compartment (Vc), total volume of distribution (Vd), and intercompartment transfer constants were 1.93 (5.11) mL/min/kg, 0.27 (0.25) L/ kg, 0.49 (0.38) L/kg, 2.49 (1.4) hr-1, and 2.64(1.1) hr-1, respectively. This resulted in a mean (SD) elimination half-life of 4.9 (6.6) hr. The CL estimate in this population of ECLS patients is significantly higher than previous estimates (0.5-1mL/kg/min) with older oxygenators with a similar Vd with a contemporary ECLS arrangement.  
   Conclusion:  These are the first VAN PK data in neonates with a contemporary ECLS operation utilizing the Quadrox oxygenator demonstrating significantly higher CL values with a similar Vd.

Original language	American English
State	Published - Jun 2016
Event	The Journal of Pediatric Pharmacology and Therapeutics 25th Annual Meeting - Duration: Jun 1 2016 → …

Conference

Conference	The Journal of Pediatric Pharmacology and Therapeutics 25th Annual Meeting
Period	6/1/16 → …

Keywords

ECLS
PK
VAN
Vancomycin
extra-corporeal life support
neonates
pharmacokinetics

Disciplines

Medicine and Health Sciences
Medical Sciences
Pharmacy and Pharmaceutical Sciences
Other Pharmacy and Pharmaceutical Sciences

Cite this

@conference{06bd450ae0994eef953f14c237a903ee,

title = "Population Pharmacokinetics (PK) of Vancomycin (VAN) in Neonates on Extra-Corporeal Life Support (ECLS)",

abstract = " Introduction: VAN remains first line therapy for the treatment of life-threatening infections caused by methicillin resistant Staphylococcus aureus (MRSA) and ampicillin resistant Enterococci. Current evidence suggests that VAN trough levels of 15-20 mg/L or an AUC:MIC ratio of 400:1 are needed to maximize outcomes. Many factors can affect VAN PK in the pediatric ICU including sepsis and ECLS. Currently, no VAN PK data exists for children on ECLS with the current ECLS equipment. The purpose of this study was to describe VAN PK in children with a contemporary ECLS operation, including the Quadrox oxygenator Methods: During the ECLS run, routine blood samples were collected from 14 neonates who received VAN for prophylaxis or empiric therapy. VAN concentrations were measured by fluorescent polarization and the population PK was determined using PMetrics. Multiple compartmental and covariate models were explored to determine the best fit of the data. Results: 13 neonates with a median gestational age of 36 weeks accounted for 16 VAN treatment courses. Each course contributed a median of 8 VAN levels (3-27) to the model. A 2 compartment model with weight as a covariate fit the VAN concentration data the best. Mean (SD) population estimates for clearance (CL), volume of the central compartment (Vc), total volume of distribution (Vd), and intercompartment transfer constants were 1.93 (5.11) mL/min/kg, 0.27 (0.25) L/ kg, 0.49 (0.38) L/kg, 2.49 (1.4) hr-1, and 2.64(1.1) hr-1, respectively. This resulted in a mean (SD) elimination half-life of 4.9 (6.6) hr. The CL estimate in this population of ECLS patients is significantly higher than previous estimates (0.5-1mL/kg/min) with older oxygenators with a similar Vd with a contemporary ECLS arrangement. Conclusion: These are the first VAN PK data in neonates with a contemporary ECLS operation utilizing the Quadrox oxygenator demonstrating significantly higher CL values with a similar Vd.",

keywords = "ECLS, PK, VAN, Vancomycin, extra-corporeal life support, neonates, pharmacokinetics",

author = "Knoderer, \{Chad A.\} and Nichols, \{Kristen R.\} and Jeffrey Cies and Wayne Moore and Dominick Carella and Jason Parker and Paul Shea and Arun Chopra",

year = "2016",

month = jun,

language = "American English",

note = "The Journal of Pediatric Pharmacology and Therapeutics 25th Annual Meeting ; Conference date: 01-06-2016",

}

TY - CONF

T1 - Population Pharmacokinetics (PK) of Vancomycin (VAN) in Neonates on Extra-Corporeal Life Support (ECLS)

AU - Knoderer, Chad A.

AU - Nichols, Kristen R.

AU - Cies, Jeffrey

AU - Moore, Wayne

AU - Carella, Dominick

AU - Parker, Jason

AU - Shea, Paul

AU - Chopra, Arun

PY - 2016/6

Y1 - 2016/6

N2 - Introduction: VAN remains first line therapy for the treatment of life-threatening infections caused by methicillin resistant Staphylococcus aureus (MRSA) and ampicillin resistant Enterococci. Current evidence suggests that VAN trough levels of 15-20 mg/L or an AUC:MIC ratio of 400:1 are needed to maximize outcomes. Many factors can affect VAN PK in the pediatric ICU including sepsis and ECLS. Currently, no VAN PK data exists for children on ECLS with the current ECLS equipment. The purpose of this study was to describe VAN PK in children with a contemporary ECLS operation, including the Quadrox oxygenator Methods: During the ECLS run, routine blood samples were collected from 14 neonates who received VAN for prophylaxis or empiric therapy. VAN concentrations were measured by fluorescent polarization and the population PK was determined using PMetrics. Multiple compartmental and covariate models were explored to determine the best fit of the data. Results: 13 neonates with a median gestational age of 36 weeks accounted for 16 VAN treatment courses. Each course contributed a median of 8 VAN levels (3-27) to the model. A 2 compartment model with weight as a covariate fit the VAN concentration data the best. Mean (SD) population estimates for clearance (CL), volume of the central compartment (Vc), total volume of distribution (Vd), and intercompartment transfer constants were 1.93 (5.11) mL/min/kg, 0.27 (0.25) L/ kg, 0.49 (0.38) L/kg, 2.49 (1.4) hr-1, and 2.64(1.1) hr-1, respectively. This resulted in a mean (SD) elimination half-life of 4.9 (6.6) hr. The CL estimate in this population of ECLS patients is significantly higher than previous estimates (0.5-1mL/kg/min) with older oxygenators with a similar Vd with a contemporary ECLS arrangement. Conclusion: These are the first VAN PK data in neonates with a contemporary ECLS operation utilizing the Quadrox oxygenator demonstrating significantly higher CL values with a similar Vd.

AB - Introduction: VAN remains first line therapy for the treatment of life-threatening infections caused by methicillin resistant Staphylococcus aureus (MRSA) and ampicillin resistant Enterococci. Current evidence suggests that VAN trough levels of 15-20 mg/L or an AUC:MIC ratio of 400:1 are needed to maximize outcomes. Many factors can affect VAN PK in the pediatric ICU including sepsis and ECLS. Currently, no VAN PK data exists for children on ECLS with the current ECLS equipment. The purpose of this study was to describe VAN PK in children with a contemporary ECLS operation, including the Quadrox oxygenator Methods: During the ECLS run, routine blood samples were collected from 14 neonates who received VAN for prophylaxis or empiric therapy. VAN concentrations were measured by fluorescent polarization and the population PK was determined using PMetrics. Multiple compartmental and covariate models were explored to determine the best fit of the data. Results: 13 neonates with a median gestational age of 36 weeks accounted for 16 VAN treatment courses. Each course contributed a median of 8 VAN levels (3-27) to the model. A 2 compartment model with weight as a covariate fit the VAN concentration data the best. Mean (SD) population estimates for clearance (CL), volume of the central compartment (Vc), total volume of distribution (Vd), and intercompartment transfer constants were 1.93 (5.11) mL/min/kg, 0.27 (0.25) L/ kg, 0.49 (0.38) L/kg, 2.49 (1.4) hr-1, and 2.64(1.1) hr-1, respectively. This resulted in a mean (SD) elimination half-life of 4.9 (6.6) hr. The CL estimate in this population of ECLS patients is significantly higher than previous estimates (0.5-1mL/kg/min) with older oxygenators with a similar Vd with a contemporary ECLS arrangement. Conclusion: These are the first VAN PK data in neonates with a contemporary ECLS operation utilizing the Quadrox oxygenator demonstrating significantly higher CL values with a similar Vd.

KW - ECLS

KW - PK

KW - VAN

KW - Vancomycin

KW - extra-corporeal life support

KW - neonates

KW - pharmacokinetics

M3 - Presentation

T2 - The Journal of Pediatric Pharmacology and Therapeutics 25th Annual Meeting

Y2 - 1 June 2016

ER -