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Transport of drugs, hormones and fatty acids in lipemic serum.

Injection of 3.33 mg of estradiol benzoate in chickens for seven days increased average serum lipid levels as follows: free fatty acids from 490 to 7800 µEq/1, total lipid from 1270 to 17,600 mg/100 ml, triglyceride from 140 to 13,400 mg/100 ml, cholesterol from 140 to 1200 mg/100 ml and phospholipid from 170 to 250 mg/100 ml. These changes in serum lipids were associated with increased binding by the serum of the following ligands as measured by dialysis-equilibrium: diphenylhydantoin, bishydroxycoumarin, estradiol, testosterone, palmitate, oleate, pentobarbital and aldosterone. When the serum was fractionated by centrifugation at 100,000 x g into top fraction (containing the lipoproteins) and bottom fraction (containing albumin and steroid-binding proteins), the increased binding capacity of the lipemic serum was found to reside in the top (lipoprotein) fraction. Binding of salicylate, digitoxin, digoxin, cortisol and octanoate, as measured by dialysis-equilibrium, was not influenced by lipemia. Addition of ligand directly to the serum, followed by centrifugation at 100,000 x g , showed that a portion of the following ligands was recovered in the lipoprotein fraction, the magnitude of this recovery being proportional to the degree of lipemia: diphenylhydantoin, bishydroxycoumarin, estradiol. testosterone, palmitate, oleate, pentobarbital and aldosterone. In contrast, salicylate, digitoxin, digoxin, cortisol and octanoate were not found in the lipoprotein phase of the lipemic serum. The tendency of the 13 ligands to be sequestered by the lipoproteins, as revealed by dialysis-equilibrium and direct centrifugal experiments, was correlated with the partition coefficient of the ligand in chloroform/pH 7.4 sodium phosphate buffer. Those ligands with partition coefficient iLs11 were subject to sequestration in lipoprotein. Ligands with partition coefficient iLs11 were similarly redistributed into the lipoprotein phase of the following types of lipemic serum: lipemia produced in the rabbit by repeated injection of fat-mobilizing pituitary extract, lipemia produced in the rabbit by a 2% cholesterol diet for two to six months and two types of hereditary human lipemia.