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 infusion 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 concentration 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 not affected by the infusion rate. Ureter-ligated (UL) and control rats received an intravenous infusion of CFSL at 1.4 g/h/rat until the onset of seizures. Then the same procedure as used to determine the effect of infusion rate on the concentrations of CFSL was carried out. Renal failure was associated with a significant decrease in the amount of CFSL required to induce seizures. Serum, brain, and CSF concentrations of CFSL in UL rats were significantly lower than those in control rats. These results indicate that the experimental strategy and animal model in this investigation would be useful to assess the effects of diseases and other variables on the pharmacodynamics of CFSL-induced seizures and that renal failure is one of the risk factors for neurotoxicity of CFSL.
Nagata
M
M
Department of Hospital Pharmacy, School of Medicine, Tokyo Medical and Dental University, Japan.
Yasuhara
M
M
D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism*; D000818:Animals; D015296:Ceftizoxime / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000633:toxicity*; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000633:toxicity*; D003292:Convulsants / Q000493:pharmacokinetics* / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism
D002511:Cephalosporins; D003292:Convulsants; C079769:cefoselis; D015296:Ceftizoxime