Protein binding of flucloxacillin in neonates

Area of Science:

• Pharmacology
• Neonatal Medicine
• Analytical Chemistry

Background:

• Isoxazolyl penicillins, like flucloxacillin, exhibit high plasma protein binding.
• Only the unbound fraction of flucloxacillin is pharmacologically active.
• Limited data exists on flucloxacillin protein binding in newborn infants.

Purpose of the Study:

• To investigate flucloxacillin protein binding in a cohort of preterm infants.
• To determine factors influencing flucloxacillin protein binding in this population.
• To assess the implications for optimizing flucloxacillin dosing in neonates.

Main Methods:

• Ultrafiltration was used to separate free and protein-bound flucloxacillin.
• Reversed-phase high-performance liquid chromatography (HPLC) with UV detection quantified flucloxacillin concentrations.
• Plasma samples from 56 preterm infants (3-87 days old) were analyzed.

Main Results:

• Mean flucloxacillin protein binding was 74.5% ± 13.1%, with significant inter-infant variability (34.3%–89.7%).
• Strong positive correlation found between protein binding and plasma albumin concentration (r = 0.804).
• Significant negative correlation observed between protein binding and plasma creatinine concentration (r = -0.601).

Conclusions:

• High variability in flucloxacillin protein binding complicates standard dosing regimens for infants.
• Individualized dosing based on free flucloxacillin levels could optimize treatment for neonatal sepsis.
• Routine measurement of free flucloxacillin is likely impractical in neonatal care settings.