Decreased protein binding of moxifloxacin in patients with sepsis?

Abstract

The mean (SD) unbound fraction of moxifloxacin in plasma from patients with severe sepsis or septic shock was determined by ultrafiltration to 85.5±3.0% (range 81.9 and 91.6%) indicating a decreased protein binding of moxifloxacin in this population compared with the value of 58-60% provided in the Summary of Product Characteristics. However, previous investigations neglected the influence of pH and temperature on the protein binding of moxifloxacin. Maintaining physiological conditions (pH 7.4, 37°C) - as in the present study - the unbound fraction of moxifloxacin in plasma from healthy volunteers was 84%. In contrast, the unbound fraction of moxifloxacin was 77% at 4°C and 66-68% in unbuffered plasma or at pH 8.5 in fair agreement with previously published data. PK/PD parameters e.g. fAUC/MIC or ratios between interstitial fluid and free plasma concentrations, which were obtained assuming a protein binding rate of moxifloxacin of 40% or more, should be revised.

Keywords: fluoroquinolone; septic shock; ultrafiltration; unbound fraction.

Figure 1. Unbound fraction (fu) of moxifloxacin in plasma of ICU patients with sepsis treated with moxifloxacin 400 mg i.v. once daily

Median, IQR, circles = mean values of 6 samples per patient, dotted line = fu in pool plasma from healthy volunteers

Figure 2. Influence of temperature on the protein binding of moxifloxacin in human plasma, buffered with potassium phosphate to 7.4, as determined by ultrafiltration. Mean±SD of 4 independent experiments with moxifloxacin 3 or 0.3 mg/L (n=8)

Figure 3. Influence of pH on the protein binding of moxifloxacin in human plasma (at 37°C) as determined by ultrafiltration. Mean±SD of 4 independent experiments with moxifloxacin 3 or 0.3 mg/L (total n=8)

Abbr.: P phosphate, H HEPES, T TRIS, Pl plasma unbuffered