Alpha 1-acid glycoprotein and albumin in human serum bupivacaine binding

Bupivacaine protein binding was studied with the use of human serum, isolated human serum albumin, and isolated alpha 1-acid glycoprotein. The effect of lactic acid on bupivacaine binding was also studied. Bupivacaine protein binding in serum is best characterized by a model described by two classes of binding sites and that in alpha 1-acid glycoprotein or albumin is best characterized by a model described by one class of binding sites for each protein. Albumin binding closely correlated with the data obtained for the low-affinity, high-capacity binding site in serum, while alpha 1-acid glycoprotein data closely correlated with the data obtained for the high-affinity, low-capacity site in serum. A reduction in pH resulted in a significant reduction in the affinity for the high-affinity, low-capacity site in serum. No other binding parameters were affected. These data were in excellent agreement with results of the isolated protein studies. Our data demonstrate that acidosis results in significant increases in free bupivacaine concentrations only at relatively low total bupivacaine concentrations (less than 7 micrograms/ml) and that distribution characteristics for bupivacaine are essentially unchanged over a wide concentration range.