Effect of experimental renal failure on the pharmacodynamics of cefoselis-induced seizures in rats

We investigated the effect of infusion rate and experimental renal failure on the pharmacodynamics of cefoselis (CFSL)-induced seizures. As an animal model of CFSL-induced seizures, male Wistar rats received an intravenous in fusion of CFSL at one of three different rates (1.4-5.8 g/h/rat) until the onset of maximal seizures (which occurred after 8.0 to 36.0 min of infusion ). Samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately after stopping infusion of CSFL. The serum concentrati on of CFSL at the onset of seizures increased with increasing infusion rate , but brain and CSF concentrations of CFSL at the onset of seizures were no t affected by the infusion rate. Ureter-ligated (UL) and control rats recei ved an intravenous infusion of CFSL at 1.4 g/h/rat until the onset of seizu res. Then the same procedure as used to determine the effect of infusion ra te on the concentrations of CFSL was carried out. Renal failure was associa ted with a significant decrease in the amount of CFSL required to induce se izures. Serum, brain, and CSF concentrations of CFSL in UL rats were signif icantly lower than those in control rats. These results indicate that the e xperimental strategy and animal model in this investigation would be useful to assess the effects of diseases and other variables on the pharmacodynam ics of CFSL-induced seizures and that renal failure is one of the risk fact ors for neurotoxicity of CFSL.