Protein binding characteristics of bumetanide

The association constants (k) and binding capacities (np) of bumetanide were determined in pooled venous blood obtained from adults, venous cord blood of healthy full-term infants, and critically ill neonates using ultrafiltration. Bumetanide was highly bound to plasma proteins (approximately 97%) in all three populations studied. Two classes of binding sites were identified, a high-affinity, low-capacity site with k and np in the order of 10(3) M-1 and 10(-3) M, respectively, and a low-affinity, high-capacity site with k and np in the order of 10(2) M-1 and 10(-2) M, respectively. Binding capacities were similar between the three groups studied and were larger than the 'presumed' therapeutic concentration following intravenous administration of the drug, which is on the order of 10(-6) M (less than or equal to 0.5 microgram/ml).