Factors Influencing Serum Protein Binding of Lidocaine in Humans

Abstract

Several factors that may affect protein binding of lidocaine in human serum were studied in normal volunteers. Evidence was obtained for the presence of two classes of lidocaine binding sites with strikingly different affinity constants (k) and capacities (nP); k₁ = 1.3 × 10⁵ M^-1 n₁P₁ = 1.7 × 10^-5 M, and k₂ = 6.4 × 10¹ M^-1. n₂P₂ = 6.9 × 10^-3 M. The low affinity binding sites are probably on serum albumin, whereas the high affinity site may be located on α₁ acid glycoprotein. At a lidocaine serum concentration of approximately 1.4 μg/ml, it was observed that acidosis (pH 7.4 → 7.2) caused lidocaine-free fraction to increase from 0.29 to 0.36 (p < 0.01) and that the addition of the lidocaine metabolites 3-hydroxylidocaine, 4-hydroxylidocaine, monoethylglycinexylidide, and glycinexylidide had no effect on the binding of lidocaine. Bupivacaine, disopyramide, and quinidine (in concentrations that are observed clinically) caused a significant increase (p < 0.01) in the free fraction of lidocaine in serum (23%, 21%, and 34%, respectively). Interestingly, N-depropyl disopyramide, dihydroquinidine, procainamide, N-acetyl procainamide, and propranolol had no effect on lidocaine binding.