EFFECT OF ENDOGENOUS COMPOUNDS, ISOLATED FROM SERA OF UREMIC PATIENTS, ON CHLORAMPHENICOL BINDING TO PROTEINS

Charcoal treatment (NORIT A) at pH 3 isolated hitherto unidentified endogenous compounds from uremic serum. These compounds were responsible for reduced binding of chloramphenicol to proteins in uremic patients. After treatment of uremic sera with NORIT, differences in the binding of chloramphenicol to serum proteins in healthy individuals and in uremic patients disappeared. The endogenous compounds were isolated from NORIT by elution using a mixture of 0.1 N HC 1 and ethanol (1:1). Eluates were then incubated with control serum for 2 hr at 37°C. The binding of chloramphenicol to control serum proteins decreased when eluates from uremie sera were added (P < 0.01). However, the eluate obtained from NORIT after the treatment of sera of healthy individuals did not affect the binding of chloramphenicol to serum proteins. To identify these endogenous compounds, we assessed the concentrations of free amino acids and lipids in the serum before and after NORIT treatment in both groups. Of the amino acids, uremic patients displayed significantly higher concentrations only of cystine, citrulline and 3-methylhistidine. These amino acids were adsorbed to an increased extent by NORIT (P < 0.01). However, when added to control serum, their enhanced concentrations did not affect the binding of chloramphenicol to proteins. Determination of lipid levels showed a decreased concentration of cholesterol (P < 0.05) and an increased concentration of triglycerides in uremic patients (P < 0.01). These lipids were not adsorbed by NORIT. There was no difference between free fatty acids levels in both groups. This finding suggests that free fatty acids did not cause the reduced binding of chloramphenicol to proteins in uremic patients, though they were adsorbed by NORIT. © 1979.