# Protein binding of vancomycin in a large mixed patient population at a university hospital

## TL;DR

This study finds that about 70% of vancomycin in the blood is unbound and available for treatment, with low variability across patients.

## Contribution

The study provides a reliable estimate of the unbound fraction of vancomycin in a large patient population.

## Key findings

- The mean unbound fraction of vancomycin was 72.2% with low variability.
- Unbound fraction was not influenced by demographic or biochemical factors.
- HPLC-UV and immunoassay methods showed excellent agreement for measuring vancomycin.

## Abstract

Vancomycin remains a key treatment for infections caused by β-lactam-resistant gram-positive cocci. While there is unanimity that only drug not bound to plasma proteins is pharmacologically active, a wide range of values and interdependencies for the unbound fraction (fu) of vancomycin have been reported in the past. In the present study, we evaluated 706 plasma samples from 228 adult in-patients who were sent for therapeutic drug monitoring. Total and free concentrations of vancomycin were analyzed by a validated method using ultrafiltration and HPLC-UV. Covariate effects on fu were assessed by a linear mixed-effects model. The mean unbound fraction was 72.2 ± 5.5% (coefficient of variation 7.7%, range 53–93%), the intra-individual and inter-individual variability were low (median coefficient of variation 5.7% and 6.4%, respectively). The unbound fraction was independent of total vancomycin, plasma albumin or total protein concentrations, or other biochemical or demographic variables, and did not differ between patients treated inside or outside of intensive care (P=0.465). Linear mixed-effects modeling confirmed low overall variability (coefficient of variation 7.0%), decomposed into 2.2% inter-individual, 3.8% inter-occasion, and 5.5% residual variability. Method comparison showed an excellent agreement between high-performance liquid chromatography with ultraviolet detection (HPLC-UV) and the immunoassay used for routine drug monitoring (bias +0.2%). Free concentrations of vancomycin can be reliably predicted from total concentrations. An unbound fraction of approximately 70% provides a robust and clinically useful estimate. Remaining variability appears to be primarily methodological, and not of clinical relevance.