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Interaction of albumin and fusidic acid
Abstract:
1. By combining the agar plate diffusion technique for determination of antibiotic activity and zone microelectrophoresis in agar gel, the activity of fusidic acid in individual serum proteins of blood and pus obtained from patients given sodium fusidate revealed albumin to be responsible for the protein binding of this antibiotic.2. Based on the assumption that only free fusidic acid is microbiologically active, the relationship between the concentration of albumin and the ratio of free to total fusidic acid was determined at four concentrations of free fusidic acid, using as test organisms four differently sensitive variants of a Staphylococcus aureus strain. At each concentration an increasing amount of albumin (0-40 mg/ml culture medium) decreased the activity of fusidic acid as determined in serial dilutions (IC50).3. The law of mass action expressed as Langmuir's adsorption isotherm was valid if a correction for the influence of albumin on the sensitivity of the strain of Staph. aureus was introduced. For other test organisms no correction is necessary. The constant in Langmuir's adsorption isotherm was K=78400+/-8200 l./mol and n=3.15 (95% confidence limits: 2.09-5.52).4. The mean blood concentration was 20.8 mug/ml and the mean pus concentration 17.2 mug/ml in nineteen sets of blood and pus samples. The ratio of pus to blood corresponds to the ratio of published values for the protein concentrations in serum and in inflammatory oedema.5. It is concluded that for albumin bound drugs the ;storage depot' of the organism also includes the fluid of the tissue spaces including the inflammatory oedema. As recent studies have revealed an extravascular albumin pool similar in size to the plasma pool, this ;storage depot' should not be neglected.
Insights
Fusidic acid primarily binds to albumin in the blood and pus. Albumin concentration influences fusidic acid activity, with higher albumin levels reducing its effectiveness against Staphylococcus aureus.
Area of Science:
- Pharmacology
- Microbiology
- Biochemistry
Background:
- Fusidic acid is an antibiotic used to treat Staphylococcus aureus infections.
- Understanding drug-protein binding is crucial for optimizing therapeutic efficacy.
Purpose of the Study:
- To investigate the protein binding of fusidic acid in biological fluids.
- To determine the relationship between albumin concentration and fusidic acid activity.
Main Methods:
- Agar plate diffusion assay combined with zone microelectrophoresis.
- Testing fusidic acid activity against Staphylococcus aureus variants at varying albumin concentrations.
- Applying Langmuir's adsorption isotherm to model the binding interaction.
Main Results:
- Albumin was identified as the primary serum protein binding fusidic acid.
- Increased albumin concentration (0-40 mg/ml) decreased fusidic acid's microbiological activity (IC50).
- Langmuir's adsorption isotherm accurately described the binding with a constant K=78400+/-8200 l./mol and n=3.15.
Conclusions:
- Albumin acts as a significant binding protein for fusidic acid.
- Tissue fluid spaces, including inflammatory edema, serve as a 'storage depot' for albumin-bound drugs.
- This extravascular albumin pool is comparable to the plasma pool and impacts drug distribution.