PMID- 25072945
OWN - NLM
STAT- MEDLINE
DCOM- 20151203
LR  - 20150315
IS  - 1536-3694 (Electronic)
IS  - 0163-4356 (Linking)
VI  - 37
IP  - 2
DP  - 2015 Apr
TI  - Measuring unbound versus total vancomycin concentrations in serum and plasma: 
      methodological issues and relevance.
PG  - 180-7
LID - 10.1097/FTD.0000000000000122 [doi]
AB  - BACKGROUND: Studies on the unbound fraction (fu) of vancomycin report highly 
      variable results. Great controversy also exists about the correlation between 
      unbound and total vancomycin concentrations. As differences in (pre-)analytic 
      techniques may explain these findings, we investigated the impact of the 
      procedure used to isolate unbound vancomycin in serum/plasma on fu and the 
      correlation between total and unbound concentrations. METHODS: Patient samples (n 
      = 39) were analyzed for total and unbound vancomycin concentrations after 
      ultrafiltration (UF, Centrifree at 4 degrees C and 37 degrees C) or equilibrium dialysis (ED, 
      using a Fast Micro-Equilibrium Dialyzer at 37 degrees C) on an Architect i2000SR. To 
      investigate correlations with potential binding proteins, total protein, albumin, 
      alpha-1-acid glycoprotein, and IgA concentrations were also measured. RESULTS: 
      The median fu after ED was 72.5% [interquartile range (IQR), 68.7%-75.0%]. 
      Ultrafiltration at 4 degrees C and 37 degrees C resulted in a median fu of 51.6% (IQR, 
      48.6%-54.8%) and 75.2% (IQR, 69.3%-78.6%), respectively, with no significant 
      difference between unbound vancomycin concentrations after ED and UF at 37 degrees C (P = 
      0.13). Unbound concentrations obtained through ED and UF correlated linearly 
      (4 degrees C: r = 0.9457; 37 degrees C: r = 0.9478; both P < 0.0001). Linear mixed-model 
      regression showed that total vancomycin as such was the predominant determinant 
      for the unbound concentration, allowing a reliable prediction (mean bias +/- SD, 
      5.0% +/- 7.6%). The studied protein concentrations were of no added value in 
      predicting the unbound concentration. CONCLUSIONS: Vancomycin fu after UF at 4 degrees C 
      was on average 30.6% lower than that after UF at 37 degrees C, demonstrating the 
      importance of temperature during UF. Ultrafiltration at 37 degrees C resulted in unbound 
      vancomycin concentrations equivalent with ED. As the unbound concentration could 
      be reliably predicted based on total vancomycin concentrations as such, 
      measurement of unbound vancomycin concentrations has little added value over 
      measurements of total vancomycin concentrations.
FAU - Stove, Veronique
AU  - Stove V
AD  - *Department of Laboratory Medicine, Ghent University Hospital; daggerDepartment of 
      Clinical Chemistry, Microbiology and Immunology, Ghent University; and 
      double daggerDepartment of Critical Care Medicine, Ghent University Hospital, Belgium.
FAU - Coene, Louise
AU  - Coene L
FAU - Carlier, Mieke
AU  - Carlier M
FAU - De Waele, Jan J
AU  - De Waele JJ
FAU - Fiers, Tom
AU  - Fiers T
FAU - Verstraete, Alain G
AU  - Verstraete AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ther Drug Monit
JT  - Therapeutic drug monitoring
JID - 7909660
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Blood Proteins)
RN  - 6Q205EH1VU (Vancomycin)
SB  - IM
EIN - Ther Drug Monit. 2015 Aug;37(4):554
MH  - Anti-Bacterial Agents/*blood/metabolism
MH  - Blood Proteins/*metabolism
MH  - Humans
MH  - Linear Models
MH  - Reproducibility of Results
MH  - Temperature
MH  - *Ultrafiltration
MH  - Vancomycin/*blood/metabolism
EDAT- 2014/07/30 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/07/30 06:00
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1097/FTD.0000000000000122 [doi]
PST - ppublish
SO  - Ther Drug Monit. 2015 Apr;37(2):180-7. doi: 10.1097/FTD.0000000000000122.