Decreased protein binding of moxifloxacin in patients with sepsis?

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Biochemistry

Background:

• Moxifloxacin protein binding is crucial for its efficacy.
• Previous studies may not have adequately controlled for pH and temperature, affecting binding results.
• Altered protein binding in sepsis can impact drug distribution and therapeutic outcomes.

Purpose of the Study:

• To determine the unbound fraction of moxifloxacin in plasma from patients with severe sepsis or septic shock.
• To investigate the influence of pH and temperature on moxifloxacin protein binding.
• To re-evaluate the necessity of revising pharmacokinetic/pharmacodynamic (PK/PD) parameters based on new binding data.

Main Methods:

• Ultrafiltration was used to measure the unbound fraction of moxifloxacin in plasma.
• Plasma samples were obtained from patients with severe sepsis or septic shock and healthy volunteers.
• Experiments were conducted under controlled physiological conditions (pH 7.4, 37°C) and varied conditions (4°C, unbuffered, pH 8.5).

Main Results:

• The unbound fraction of moxifloxacin in septic patients was significantly higher (85.5±3.0%) compared to the Summary of Product Characteristics (58-60%).
• Under physiological conditions, the unbound fraction in healthy volunteers was 84%.
• Lower unbound fractions were observed at 4°C (77%) and in unbuffered or alkaline plasma (66-68%).

Conclusions:

• Moxifloxacin exhibits decreased protein binding in patients with severe sepsis or septic shock.
• Physiological factors like pH and temperature significantly influence moxifloxacin protein binding.
• Existing PK/PD parameters, particularly those assuming higher protein binding, require revision for accurate clinical application.