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

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.

A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function

“…The interindividual variation of vancomycin CL in the reported models ranged from 16% to 45%, and the residual variation ranged from 7% to 40% . Previous Japanese and Korean studies had shown that the interindividual variation and residual variation of the CL were smaller than that of most of the established models using Scr as the renal marker .…”

“…The guideline of therapeutic drug monitoring for vancomycin recommends that vancomycin dosage should be administered and adjusted individually based on PPK models . PPK models of vancomycin were very common, but most of them incorporated the CLcr as the renal function covariate, which are considered to be defective in estimating renal function. There were only a few PPK models developed optimal dosing regimens according to different CLcr levels .…”

Impact of Sampling Period on Population Pharmacokinetic Analysis of Antibiotics: Why do You Take Blood Samples Following the Fourth Dose?

“…We hypothesized that blood sampling does not need to be performed at steady-state levels to build a useful Pop PK model of antimicrobials but may be performed after the first drug administration. Vancomycin PK profiles were described by a one-compartment model in a sparse sampling scheme [25], while they were explained by a two-compartment model in a dense sampling scheme [26][27][28]. We chose a two-compartment model for this study because ability to predict the concentration of the two-compartment model is superior to that of the one-compartment model [29][30][31].…”

Pharmacokinetics of vancomycin in patients with different renal function levels

“…Conversely, other authors reported that patients with acute myeloid leukemia had lower clearance of vancomycin [ 26 ]. It was also noted that body weight may affect clearance of vancomycin, as an increase in weight was related to higher values of both clearance and volume of distribution [ 27 , 28 ]. Finally, some authors showed that furosemide may influence vancomycin clearance, whereas others concluded that concomitant drugs had no influence on clearance [ 29 , 21 ].…”