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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.


Dose simulation. This figure shows the result of the dose simulation for the patient of median weight (95 kg) and creatinine clearance (84 ml/min). In all, 1,000 Monte Carlo simulations were performed using the median patient at different dosage regimens. The dashed lines represent the target trough concentration. The straight curve represents the median prediction of vancomycin concentration. A dosing strategy was considered successful if it produced a trough in the target range in between the third and fifth administration of vancomycin.
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psp412112-fig-0004: Dose simulation. This figure shows the result of the dose simulation for the patient of median weight (95 kg) and creatinine clearance (84 ml/min). In all, 1,000 Monte Carlo simulations were performed using the median patient at different dosage regimens. The dashed lines represent the target trough concentration. The straight curve represents the median prediction of vancomycin concentration. A dosing strategy was considered successful if it produced a trough in the target range in between the third and fifth administration of vancomycin.

Mentions: After finalizing and demonstrating the viability of the PK model, it was used to simulate the vancomycin concentration–time profile for the patient of median bodyweight and creatinine clearance in the study. Figure 4 demonstrates the results of the dosing simulation; 1,000 mg given twice daily and 2,000 mg given daily were both able to adequately reach the selected trough region of 15–20 mg/L during steady‐state concentration. This suggests that either dose regimen of vancomycin will show therapeutic efficacy in ECMO patients with a bodyweight close to 95 kg and with a CRCL of 85 mL/min, while higher or more frequent doses would increase the possibility of supratherapeutic troughs. Given the focus on patients of high bodyweight, the dose simulation was performed in patients above median bodyweight; 3,000 mg daily in 2–3 divided doses was found to reach adequate trough concentrations in patients between 95 and 149 kg.


A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy
Dose simulation. This figure shows the result of the dose simulation for the patient of median weight (95 kg) and creatinine clearance (84 ml/min). In all, 1,000 Monte Carlo simulations were performed using the median patient at different dosage regimens. The dashed lines represent the target trough concentration. The straight curve represents the median prediction of vancomycin concentration. A dosing strategy was considered successful if it produced a trough in the target range in between the third and fifth administration of vancomycin.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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

psp412112-fig-0004: Dose simulation. This figure shows the result of the dose simulation for the patient of median weight (95 kg) and creatinine clearance (84 ml/min). In all, 1,000 Monte Carlo simulations were performed using the median patient at different dosage regimens. The dashed lines represent the target trough concentration. The straight curve represents the median prediction of vancomycin concentration. A dosing strategy was considered successful if it produced a trough in the target range in between the third and fifth administration of vancomycin.
Mentions: After finalizing and demonstrating the viability of the PK model, it was used to simulate the vancomycin concentration–time profile for the patient of median bodyweight and creatinine clearance in the study. Figure 4 demonstrates the results of the dosing simulation; 1,000 mg given twice daily and 2,000 mg given daily were both able to adequately reach the selected trough region of 15–20 mg/L during steady‐state concentration. This suggests that either dose regimen of vancomycin will show therapeutic efficacy in ECMO patients with a bodyweight close to 95 kg and with a CRCL of 85 mL/min, while higher or more frequent doses would increase the possibility of supratherapeutic troughs. Given the focus on patients of high bodyweight, the dose simulation was performed in patients above median bodyweight; 3,000 mg daily in 2–3 divided doses was found to reach adequate trough concentrations in patients between 95 and 149 kg.

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.