THE INTERACTION OF BARBITURATES WITH SERUM ALBUMIN AND ITS POSSIBLE RELATION TO THEIR DISPOSITION AND PHARMACOLOGICAL ACTIONS

¹ The Army Medical Service Graduate School, Walter Reed Army Medical Center and Department of Pharmacology, The George Washington University School of Medicine, Washington, D. C.

Ultrafiltration studies show that the reversible binding to bovine serum albumin of a series of barbiturates is related to the length and nature of the side chains. Binding is related to acidity, being maximal at about pH 7.8 to 8.0. With increasing drug concentration the fraction bound decreases but the total amount bound increases. With increasing protein concentration the fraction of drug bound approaches a maximum.

Thiopental is more strongly bound than comparable barbiturates and will partially displace the latter from serum albumin. Thiopental in turn may be displaced by sodium lauryl sulfonate.

Rabbit tissue homogenates are capable of binding larger fractions of barbiturate than can be accounted for by their serum albumin content. The extent of binding in vitro seems related in part to the distribution of the drugs in vivo. The extent of protein binding correlates fairly well with the known pharmacological properties of the drugs.

The data on the binding of some barbiturates to serum albumin may be represented by equations similar to those employed by others to represent the binding of other small ions by serum albumin.