Effect of Free Fatty Acids on Protein Binding of Antimicrobial Agents

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Abstract
The effect of free fatty acids (FFAs) on the binding of antibiotics to human serum proteins was studied by addition of palmitic acid to albumin solutions and normal pooled serum. FFA reduced the binding of dicloxacillin, cefamandole, and sulfamethoxazole at molar ratios of FFA to albumin of >2.0. In contrast, FFA enhanced the binding of benzylpenicillin, cephalothin, and cefoxitin at physiologic molar ratios of FFA to albumin. Elevated levels of FFAs induced in vivo by heparin produced similar results with dicloxacillin and benzylpenicillin. Addition of FFA to serum, but not to albumin, reduced the binding of clindamycin and trimethoprim. That the binding of these drugs was much lower in albumin than in serum suggested the presence in serum of another antibiotic-binding protein and that FFAs can modulate binding to this protein. Binding of chloramphenicol was unaffected by FFAs. The possible clinical significance of the changes in protein binding due to FFAs is discussed.

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