Abstract
Assessment was made of the serum protein binding of cefpiramide (CPM), a cephem of very large protein binding capacity, using sera from healthy subjects (HS) and patients with chronic renal failure (CRF), applying equilibrium dialysis in vitro. The protein binding capacity of CPM in patients with CRF [hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), conservative treatment (ND)] was significantly less than that in HS and was found to be directly correlated with the serum albumin concentration. While examining the protein binding of CPM in patients with HD, binding capacity immediately following the start and completion of dialysis was found to decrease significantly compared to that of pre-dialysis patients and to be correlated inversely with a change in the non-esterified fatty acid (NEFA) content. Log nK, for expressing protein binding affinity, decreased slightly in pre-HD, CAPD, and ND patients. This decrease was particularly prominent in patients during and after HD in contrast to HS. The addition of palmitic acid (PA), a common NEFA, to pooled sera from HS caused the binding capacity of CPM to decrease, accompanied by an increase in PA concentration. The addition of warfarin was noted to have the same effect, while diazepam and digitoxin caused no change. It follows from these findings that the changes in the binding capacity of CPM during and after HD may possibly result from the increment of NEFA through heparin-induced lipase activation, with consequent competitive displacement of CPM from in and around site I (warfarin-site) on the albumin molecule or an allosteric effect on the albumin binding capacity. In conclusion, changes in the protein binding capacity of CPM in CRF patients should be taken into consideration when attempting to avoid possible side effects.
