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Age-Related Changes in Vancomycin Protein Binding: Is It Time to Take It Seriously?
Jessica Gadsby1, Lucy Stachow1, Hussain Mulla2
1Department of Pharmacy, University Hospitals of Leicester, Leicester, United Kingdom; and.
Therapeutic Drug Monitoring
|April 22, 2024
Summary
Free vancomycin concentrations (EFVC) differ significantly in neonates and children compared to adults. Relying on total vancomycin concentrations can lead to inaccurate dosing and potentially toxic levels in pediatric patients.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Drug Monitoring
Background:
- Vancomycin (VAN) protein binding varies with patient age and illness severity.
- Dosing vancomycin based on total drug concentrations can be unreliable due to altered protein binding.
- Free vancomycin concentrations are more indicative of pharmacological activity.
Purpose of the Study:
- To compare model-estimated free vancomycin concentrations (EFVC) with assumed free vancomycin concentrations (AFVC).
- To evaluate the accuracy of standard vancomycin dosing assumptions across different patient populations (neonates, children, adults).
- To assess the impact of age and critical illness on vancomycin protein binding and free concentrations.
Main Methods:
- Retrospective analysis of patient data from electronic health records.
- Identification of patient cohorts including neonates, children, and adults in intensive care and on dialysis.
- Calculation of EFVC using six established pharmacokinetic models and AFVC based on a 50% binding assumption.
- Analysis of predictors for EFVC including albumin, total protein, and dialysis status.
Main Results:
- In adults, EFVC and AFVC showed insignificant differences.
- Significant differences between EFVC and AFVC were observed in pediatric intensive care unit patients.
- Neonates exhibited substantial discrepancies between EFVC and AFVC, with higher percentages of supratherapeutic free concentrations.
- The percentage of free vancomycin within the therapeutic range was considerably lower in neonates and children than assumed.
Conclusions:
- The unbound fraction of vancomycin is higher in critically ill neonates and children than in adults.
- Total vancomycin concentrations do not reliably reflect pharmacologically active free concentrations in pediatric populations.
- Standard vancomycin dosing adjustments targeting adult therapeutic ranges may lead to supratherapeutic and potentially toxic levels in neonates and children.
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