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A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy

View Article: PubMed Central - PubMed

ABSTRACT

The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration–time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log‐likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two‐compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non‐ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher‐weight patients.

No MeSH data available.


Clinical relevance of covariates. This graph represents the calculation of covariate effects on relevant PK parameters. The shaded region represents a 20% difference from the typical value, a clinical equivalence range. The bars represent the 95% CI of parameter changes relative to each extreme of the covariate.
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psp412112-fig-0003: Clinical relevance of covariates. This graph represents the calculation of covariate effects on relevant PK parameters. The shaded region represents a 20% difference from the typical value, a clinical equivalence range. The bars represent the 95% CI of parameter changes relative to each extreme of the covariate.

Mentions: Figure 3 presents the analysis of clinical relevance of the final covariates selected. The shaded region represents the 20% difference from the typical value. The extreme values of CRCL and WT resulted in clinically significant changes to the clearance and peripheral volume parameters, respectively. The effects of the extreme values of WT on central volume showed trends towards clinical significance but appear to lack statistical significance, as the 95% CI for each crosses the line demarking the value. This suggests a potentially meaningful relationship that was unable to be fully described. The effect of CRCL on CL is further significant, as CL directly affects the AUC. In this sample, the 10th and 90th percentiles of CRCL result in a roughly 60% increase and decrease in the AUC from the median value, respectively.


A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy
Clinical relevance of covariates. This graph represents the calculation of covariate effects on relevant PK parameters. The shaded region represents a 20% difference from the typical value, a clinical equivalence range. The bars represent the 95% CI of parameter changes relative to each extreme of the covariate.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036424&req=5

psp412112-fig-0003: Clinical relevance of covariates. This graph represents the calculation of covariate effects on relevant PK parameters. The shaded region represents a 20% difference from the typical value, a clinical equivalence range. The bars represent the 95% CI of parameter changes relative to each extreme of the covariate.
Mentions: Figure 3 presents the analysis of clinical relevance of the final covariates selected. The shaded region represents the 20% difference from the typical value. The extreme values of CRCL and WT resulted in clinically significant changes to the clearance and peripheral volume parameters, respectively. The effects of the extreme values of WT on central volume showed trends towards clinical significance but appear to lack statistical significance, as the 95% CI for each crosses the line demarking the value. This suggests a potentially meaningful relationship that was unable to be fully described. The effect of CRCL on CL is further significant, as CL directly affects the AUC. In this sample, the 10th and 90th percentiles of CRCL result in a roughly 60% increase and decrease in the AUC from the median value, respectively.

View Article: PubMed Central - PubMed

ABSTRACT

The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration–time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log‐likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two‐compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non‐ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher‐weight patients.

No MeSH data available.