Factors influencing the protein binding of vancomycin

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Abstract
Various factors influencing the protein binding of vancomycin were examined using equilibrium dialysis method. Four per cent human serum albumin (HSA) and/or 0·08 per cent alpha‐1‐acid glycoprotein (AAG), dissolved in isotonic phosphate buffer, were dialyzed against isotonic phosphate buffer of pH 7·4 using Spectrapor 2 membrane. The protein binding of vancomycin to 0·08 per cent AAG was dependent on vancomycin concentrations; the values ranged from 21·1 per cent at the vancomycin concentration of 20 μg ml−1 to 5·30 per cent at 2400 μg ml−1. However, binding to 4 per cent HSA was relatively constant, 8·79 ± 2·43 per cent over a vancomycin concentration range of 20–2400 μg ml−1. The values to 4 per cent HSA alone and 0·08 per cent AAG alone did not predict the greater binding of vancomycin in the presence of both proteins, especially at higher concentrations of vancomycin; the values to 4 per cent HSA with 0·08 per cent AAG were constant, 26·3 ± 3·74 per cent, at the vancomycin concentration range of 20–2400 μg ml−1. This suggested an interaction between the proteins, which resulted in enhanced binding of vancomycin. The protein binding of vancomycin to 4 per cent HSA with 0·08 per cent AAG was not influenced by the different incubation temperatures (4°, 22°, and 37°), quantities of heparin (up to 40 units ml−1) or AAG (up to 0·16 per cent), or buffers (isotonic phosphate buffer of pH 7·4, phosphate buffer of pH 7·4 and 0·9 per cent NaCl solution) at the vancomycin concentration of 80 μg ml−1. Vancomycin was found to be stable in human serum albumin or in isotonic phosphate buffer of pH 7·4.