A theoretical analysis of the distribution of quinidine in the plasma: the relationship between protein binding and therapeutic drug levels

Abstract

Quinidine is bound at two sets of sites on serum albumin. The distribution between the free and albumin bound form of the drug in plasma was analyzed by the use of a computer program using known association constants and binding capacities. The analysis was limited to concentrations of drug which ranged from subtherapeutic to toxic levels, 1 to 10 mg/L. The computations showed that 74 to 88% of the drug would be bound by serum albumin and the remainder would be free. Of the bound drug, 71-74% would be bound by the high affinity set of sites and the remainder by the low affinity set. The analysis also showed that if the concentration of protein were decreased, as in hypoalbuminemia, there would be a decrease in the amount of bound drug and an increase in the amount of free drug. The quantitative relationships between therapeutic levels of the drug and its distribution in plasma are discussed.