1. Int J Antimicrob Agents. 2009 Dec;34(6):555-60. Epub 2009 Sep 26.

Correlation between free and total vancomycin serum concentrations in patients
treated for Gram-positive infections.

Berthoin K, Ampe E, Tulkens PM, Carryn S.

Unité de Pharmacologie Cellulaire et Moléculaire & Louvain Drug Research
Institute, Université Catholique de Louvain, UCL 7370 Avenue E Mounier 73,
B-1200, Brussels, Belgium.

Routine therapeutic drug monitoring (TDM) reports only total vancomycin (VAN)
concentrations, although protein binding varies and it is generally accepted that
only free VAN is active. The aims of this study were to examine the correlation
between free and total VAN concentrations in order to estimate whether free VAN
levels can be predicted based on its total concentration. A high-performance
liquid chromatography (HPLC) method was set up and validated (against routine
laboratory immunoassays) for measurement of free [ultrafiltration (Centrifree);
cut-off 30 kDa] and total [solid-phase extraction (Oasis MCX cartridge)] VAN in
serum. Samples (n=65) from patients (n=15) treated by continuous infusion were
analysed. There was a wide variation in free to total VAN ratios [range 12-100%; 
mean 63.6+/-25.8%, with 59 values falling outside the 95% confidence interval
(57.3-69.9%); median 70.2%]. The correlation between free and total VAN was poor 
(R(2)=0.55). Artefacts such as pH variation of sera could be excluded. Both
intrapatient and interpatient variabilities were large and no correlation could
be made with patients' clinical conditions. Total VAN concentration is not
predictive of free VAN concentration, suggesting that actual determination of
free VAN might be recommended as an improved method of TDM.

PMID: 19782538 [PubMed - in process]