[Protein binding of various cephems in healthy subjects and patients with chronic renal failure].
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.
Kuroyama
M
M
Department of Pharmacy, Kitasato University Hospital, Kanagawa, Japan.
Kumano
K
K
Tomonaga
F
F
Sakai
T
T
Mashimo
S
S
D000328:Adult; D002511:Cephalosporins / Q000009:adverse effects / Q000378:metabolism*; D002512:Cephalothin / Q000009:adverse effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008049:Lipase; D008297:Male; D008875:Middle Aged; D009070:Moxalactam / Q000009:adverse effects / Q000378:metabolism*; D010530:Peritoneal Dialysis; D011485:Protein Binding; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism*
D002511:Cephalosporins; D005230:Fatty Acids, Nonesterified; D012709:Serum Albumin; D008049:Lipase; C036666:cefpiramide; D002512:Cephalothin; D009070:Moxalactam