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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.


Predictive checks. (a) Visual predictive check. The black circles represent the observed vancomycin concentrations. The black line represents the median concentrations from the simulations. The gray shaded area represents the 2.5th and 97.5th percentile of the simulated data points to denote a 95% CI. The five uppermost points represent concentrations from one patient who was considered an outlier in this analysis. b–d: Clinical predictive check. The histogram represents posterior predictive distribution of noncompartmental clearance (b), AUC (c), and trough concentration (d) from the 1,000 simulated datasets. The black line represents the mean of the observed data. The gray lines represent the median and 2.5th and 97.5th percentiles of the simulated datasets.
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psp412112-fig-0002: Predictive checks. (a) Visual predictive check. The black circles represent the observed vancomycin concentrations. The black line represents the median concentrations from the simulations. The gray shaded area represents the 2.5th and 97.5th percentile of the simulated data points to denote a 95% CI. The five uppermost points represent concentrations from one patient who was considered an outlier in this analysis. b–d: Clinical predictive check. The histogram represents posterior predictive distribution of noncompartmental clearance (b), AUC (c), and trough concentration (d) from the 1,000 simulated datasets. The black line represents the mean of the observed data. The gray lines represent the median and 2.5th and 97.5th percentiles of the simulated datasets.

Mentions: The goodness‐of‐fit plots (Figure 1) revealed no systemic bias. In general, there was good agreement between the predicted and observed vancomycin concentrations for the subjects in this analysis. However, the model for one patient resulted in significant underprediction of vancomycin concentrations. The VPC is shown in Figure 2a. This shows that the model was successful in predicting the concentrations seen in the samples, with the exception of the aforementioned patient. The goodness‐of‐fit is further demonstrated in the individual plots of observed concentration, individual prediction, and population prediction in Supplementary Figure 1.


A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy
Predictive checks. (a) Visual predictive check. The black circles represent the observed vancomycin concentrations. The black line represents the median concentrations from the simulations. The gray shaded area represents the 2.5th and 97.5th percentile of the simulated data points to denote a 95% CI. The five uppermost points represent concentrations from one patient who was considered an outlier in this analysis. b–d: Clinical predictive check. The histogram represents posterior predictive distribution of noncompartmental clearance (b), AUC (c), and trough concentration (d) from the 1,000 simulated datasets. The black line represents the mean of the observed data. The gray lines represent the median and 2.5th and 97.5th percentiles of the simulated datasets.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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

psp412112-fig-0002: Predictive checks. (a) Visual predictive check. The black circles represent the observed vancomycin concentrations. The black line represents the median concentrations from the simulations. The gray shaded area represents the 2.5th and 97.5th percentile of the simulated data points to denote a 95% CI. The five uppermost points represent concentrations from one patient who was considered an outlier in this analysis. b–d: Clinical predictive check. The histogram represents posterior predictive distribution of noncompartmental clearance (b), AUC (c), and trough concentration (d) from the 1,000 simulated datasets. The black line represents the mean of the observed data. The gray lines represent the median and 2.5th and 97.5th percentiles of the simulated datasets.
Mentions: The goodness‐of‐fit plots (Figure 1) revealed no systemic bias. In general, there was good agreement between the predicted and observed vancomycin concentrations for the subjects in this analysis. However, the model for one patient resulted in significant underprediction of vancomycin concentrations. The VPC is shown in Figure 2a. This shows that the model was successful in predicting the concentrations seen in the samples, with the exception of the aforementioned patient. The goodness‐of‐fit is further demonstrated in the individual plots of observed concentration, individual prediction, and population prediction in Supplementary Figure 1.

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.