Factors influencing serum protein binding of lidocaine in humans.

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 equals 1.3 x 10(5)M(-1), n1P1 equals 1.7 x 10(-5)M, and k2 equals 6.4 x 10(1)M(-1), n2P2 equals 6.9 x 10(-3)M. The low affinity binding sites are probably on serum albumin, whereas the high affinity site may be located on alpha 1 acid glycoprotein. At a lidocaine serum concentration of approximately 1.4 microgram/ml, it was observed that acidosis (pH 7.4 leads to 7.2) caused lidocaine-free fraction to increase from 0.29 to 0.36 (p less than 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 less than 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.