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Abstract: PO2019

Exploring Population Pharmacokinetic Models in Patients Treated with Vancomycin During Continuous Venovenous Hemodiafiltration (CVVHDF) on Different Anticoagulant Modalities

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Kirwan, Marcus, Trinity College Dublin Faculty of Health Sciences, Dublin, Ireland
  • Coyle, Mary, Tallaght University Hospital, Dublin, Dublin, Ireland
  • Kelly, Yvelynne P., Tallaght University Hospital, Dublin, Ireland
  • Deasy, Evelyn, Tallaght University Hospital, Dublin, Dublin, Ireland
  • Donnelly, Maria, Tallaght University Hospital, Dublin, Ireland
  • D'Arcy, Deirdre M., Trinity College Dublin Faculty of Health Sciences, Dublin, Ireland
Background

Achievement of target concentrations for antibiotics using therapeutic dose monitoring (TDM) is particularly challenging in septic patients requiring renal replacement therapy.

Methods

We conducted an exploratory population pharmacokinetic (PK) analysis in our tertiary level intensive care unit (ICU) on PK of vancomycin following intermittent infusion in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF). Clinical, laboratory and dialysis data were extracted from the electronic healthcare record (EHR) using strict inclusion criteria. A population PK analysis was conducted with a one compartment model using the PMetrics population PK modelling package. A base structural model was developed and further analyses were performed with clinical and dialysis-related data, including regional citrate anti-coagulation (RCA) vs non-RCA, to improve model prediction through covariate inclusion. The final selected model simulated patient concentrations using probability of target attainment (PTA) plots to investigate the probability of different dosing regimens achieving target therapeutic concentrations.

Results

107 vancomycin dosing intervals (155 levels) in 24 patients were examined. An acceptable base model was produced (Plots of observed vs. population predicted concentrations (Obs-Pred) R2=0.78). No continuous covariates explored resulted in a clear improvement over the base model. Use of anti-coagulation modality and vasopressor use as categorical covariates resulted in similar PK parameter estimates, with a trend towards lower parameter estimate variability both with use of RCA and without vasopressor use. Simulations using PTA plots suggested that a 2 g vancomycin loading dose followed by 750 mg 12 hourly as a maintenance dose, commencing 12 hours after loading, is required to achieve adequate early target trough concentrations of at least 15 mg/L.

Conclusion

Using robust EHR data to construct a base model from a population known to have highly heterogenous antimicrobial PK, simulations based on PTA plots showed that we could achieve acceptable trough vancomycin concentrations early in treatment with a 2 g loading dose and a maintenance dose of 750 mg 12 hourly for ICU patients on CVVHDF.