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Factors affecting ceftriaxone plasma protein binding during open heart surgery
G L Jungbluth1, M T Pasko, W J Jusko
1Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
Journal of Pharmaceutical Sciences
|October 1, 1989
Summary
Reduced ceftriaxone plasma protein binding in open heart surgery (OHS) patients is linked to lower albumin and higher free fatty acids (FFA). These factors, not pH or other proteins, significantly alter ceftriaxone levels.
Area of Science:
- Pharmacokinetics
- Clinical Chemistry
Background:
- Ceftriaxone is a widely used antibiotic.
- Plasma protein binding influences drug efficacy and distribution.
- Open heart surgery (OHS) patients exhibit altered physiological conditions.
Purpose of the Study:
- To investigate factors affecting ceftriaxone plasma protein binding in OHS patients.
- To identify specific physiological changes responsible for altered binding.
Main Methods:
- Equilibrium dialysis was used to measure ceftriaxone binding.
- In vitro experiments tested the effects of various substances (albumin, FFA, heparin, methylprednisolone) on binding.
- Patient samples from OHS underwent analysis.
Main Results:
- Albumin is the primary binding protein for ceftriaxone; lower concentrations reduce binding.
- Increased concentrations of free fatty acids (FFA) significantly decreased ceftriaxone binding.
- Binding alterations correlated with the molar ratio of FFA to albumin, not individual components.
- High-dose methylprednisolone hemisuccinate increased the free fraction of ceftriaxone.
Conclusions:
- Reduced albumin and elevated FFA concentrations are key factors in decreased ceftriaxone binding in OHS patients.
- The combined effect of low albumin and high FFA explains most observed binding changes.
- Understanding these alterations is crucial for optimizing ceftriaxone therapy in OHS patients.