Interspecies differences in plasma protein binding of beta-lactam antibiotics

Abstract

Background

Plasma protein binding (PPB) is a critical factor in drug therapy and understanding free compound exposure across preclinical and clinical species is vital for developing new antibiotics. Optimising beta-lactam dosing based on unbound drug concentrations has garnered significant interest, yet there are few data on how interspecies differences in protein binding affect the attainment of targeted unbound concentrations.

Methods

The aim of this study was to examine the protein binding of three beta-lactams, cefiderocol, ceftriaxone, and temocillin, using human, bovine, and rat plasma. Total and unbound beta-lactam concentrations were measured using ultrafiltration. An interspecies comparison of PPB was conducted to evaluate variability in protein binding across the different species.

Results

The study data showed that PPB was highest in human plasma for all three beta-lactam antibiotics tested. PPB for cefiderocol and ceftriaxone was higher in rat plasma than in bovine plasma, whereas PPB for temocillin was higher in bovine plasma than in rat plasma.

Conclusion

The study highlights substantial interspecies differences in the PPB of cefiderocol, ceftriaxone, and temocillin. The findings indicate the need for careful consideration of species-specific PPB in the optimisation of beta-lactam dosing and the development of new pharmaceuticals.