Protein binding of 14 cephems in healthy subjects and patients with chronic renal failure

• Published in: CHEMOTHERAPY Vol. 40; no. 7; pp. 898 - 908
• Main Authors: Kuroyama, Masakazu, Kumano, Kazuo, Motohashi, Shigeru, Kimura, Toshimi, Murase, Setsuko, Tomonaga, Fumiya
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1992
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.40.898

Assessment was made of the serum protein binding of 14 cephems, using sera from healthy subjects (HS) and patients with chronic renal failure (CRF), applying equilibrium dialysis under the same conditions in vitro. The protein binding capacity of the 14 cephems in patients with CRF was significantly less than that in HS, and marked increases in free drug concentrations were observed. While examining the protein binding of the 14 cephems in patients on HD, binding capacity immediately following the completion of dialysis was found to be significantly decreased as compared to that of predialysis patients. The addition of palmitic acid (PA), a common NEFA, to pooled sera from HS caused the binding capacity of ceftizoxime, cefpiramide and latamoxef to decrease, accompanied by an increase in PA concentration. While those of cephalothin were increased by increasing PA up to 3mM. It follows from these findings that changes in the binding capacities of cephems with HD may possibly be caused by increased NEFA due to activation of the lipase used in heparin as an anticoagulant. In conclusion, changes in the protein binding capacities of cephems in CRF patients should be taken into consideration in attempting to avoid potential side effects.