Serum protein-binding characteristics of vancomycin

A synthesis of studies of serum protein binding of vancomycin and its reported abnormal binding in serum with very high concentrations of immunoglobulin A (IgA) suggests that this antibiotic may be bound to more than one serum protein. Using an ultrafiltration method for separating free from bound drug and high-performance liquid chromatography to measure drug concentration, we studied the binding characteristics of vancomycin for alpha-1 acid glycoprotein, IgG, IgM, IgA, and albumin. The results showed that vancomycin does not bind to alpha-1 acid glycoprotein, IgG, or IgM. Major binding to albumin and IgA occurs, and total drug binding to serum proteins can be fully explained by binding to these two proteins. We calculated an N (number of binding sites per molecule) of 1.3 +/- 0.4 and a K (association constant) of 3.3 x 10(5) +/- 6.3 x 10(4) M-1 (NK = 4.3 x 10(5) M-1) for binding to IgA, whereas the corresponding NK value for albumin was only 527.5 M-1, indicating that vancomycin preferentially binds to IgA. Very high concentrations of IgA in serum (i.e., grams per deciliter), such as in patients with IgA myeloma, may result in the paradox of high (total) concentrations of vancomycin in serum that may be clinically ineffective.