Binding of erythromycin base to human plasma proteins

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Biochemistry and Molecular Biology

Background:

• Understanding drug binding to plasma proteins is crucial for predicting drug efficacy and toxicity.
• Erythromycin base (EB) is an antibiotic whose interactions with human plasma (HP) proteins require detailed characterization.

Purpose of the Study:

• To quantify the binding of erythromycin base (EB) to human plasma (HP) proteins at therapeutic concentrations.
• To identify the specific plasma proteins responsible for EB binding and characterize the binding kinetics.

Main Methods:

• Equilibrium dialysis using radiolabeled EB-14C at approximately 0.5 microgram/ml.
• Measurement of EB binding to purified human serum albumin (HSA) and alpha-1 acid glycoprotein (a1AGP).
• Analysis of binding kinetics, including saturable and non-saturable phenomena, and competitive binding studies.

Main Results:

• Erythromycin base (EB) exhibited 64.5% binding to human plasma (HP).
• Alpha-1 acid glycoprotein (a1AGP) was the primary binding protein (54.5% bound), followed by human serum albumin (HSA) (8.7% bound).
• EB binding to HSA was non-saturable, while binding to a1AGP was saturable. Competitive binding was observed with acetylsalicylic acid, furosemide, phenylbutazone, warfarin, and bilirubin.

Conclusions:

• Erythromycin base (EB) primarily binds to alpha-1 acid glycoprotein (a1AGP) and human serum albumin (HSA) in human plasma.
• The binding interactions involve hydrophobic, ionic, and hydrogen forces and are affected by temperature and co-administered drugs.
• These findings are essential for understanding the pharmacokinetics and potential drug interactions of erythromycin.