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This study was employed to investigate whether the serum protein binding of various cephems [cefpiramide (CPM), cefalotin (CET), latamoxef (LMOX)] differ among healthy subjects and patients with chronic renal failure (CRF) by means of in vitro equilibrium dialysis. The protein binding capacities of cephems in patients with CRF (hemodialysis, continuous ambulatory peritoneal dialysis, non-dialysis) decreased significantly compared to those in healthy subjects. The binding capacities correlated directly with total protein, albumin concentration and correlated inversely with blood urea nitrogen and serum creatinine concentration. In the study of protein binding during and after hemodialysis, the binding capacities of CPM and LMOX decreased immediately after dialysis and then increased with the time. However, the binding capacities of CET increased immediately after dialysis and then decreased. The binding capacities of CPM and LMOX correlated inversely with non-esterified fatty acids (NEFA) and those of CET correlated directly with NEFA. In the study of protein binding in pooled sera from healthy subjects with or without palmitic acid (PA), the binding capacities of CPM and LMOX decreased by increasing the concentration of PA, while those of CET increased by increasing PA up to 3 mM. The changes in binding capacity of cephems during and after hemodialysis have been possibly caused by increase of NEFA due to activation of lipase in use of heparin as an anticoagulant. In conclusion, changes in protein binding capacity of cephems in sera from CRF, which should be taken into consideration to avoid possible side effects.

A comparative study of the serum, atrial muscle, and pericardial fluid concentrations of latamoxef (LMOX) and cephalothin (CET) was performed in 18 adult patients having cardiac surgery. Patients were randomly assigned to receive either a single dose of CET 30 mg/kg, LMOX 30 mg/kg, or LMOX 20 mg/kg. Each drug was administered intravenously soon after anesthetic maintenance was achieved. After each drug administration, serum samples were obtained at various time intervals before, during, and after extracorporeal circulation (ECC), and assayed for CET and LMOX concentration. A sample of pericardial fluid was collected immediately after the pericardium was opened. The right atrial appendage tissue samples were obtained at the time of heart cannulation. The pharmacokinetics and penetration characteristics of each drug were analysed by the method of two-compartment model. Serum concentrations of CET following a single intravenous injection of 30 mg/kg were the high values, 172.4 +/- 35.6 micrograms/ml at 5 minutes, and 92.9 +/- 33.8 micrograms/ml at 15 minutes after injection. The initial (before bypass) half-life was 0.22 +/- 0.11 hour (13.1 minutes) while half-lives during and after ECC were prolonged significantly. In the cases of CET group, the myocardial tissue concentration value of 4.86 micrograms/g was obtained in only 1 case. The mean pericardial fluid concentration was 4.69 +/- 3.35 micrograms/ml at 5 to 30 minutes after injection. Serum concentration of LMOX following a injection of 30 mg/kg were 253.6 +/- 67.4 micrograms/ml at 5 minutes, and 176.3 +/- 64.1 micrograms/ml at 15 minutes after injection.(ABSTRACT TRUNCATED AT 250 WORDS)