Purpose: The purpose of this study was to investigate the effect of experimental renal failure and hypotonic hyponatremia on the pharmacodynamics of cefazolin (CEZ)-induced seizures.
Methods: Rats received an intravenous infusion of CEZ until the onset of seizures. Renal failure was produced by bilateral ureteral ligation (UL) or uranyl nitrate (UN) injection. Hypotonic hyponatremia was produced by intravenous infusion of 5% dextrose in water or intraperitoneal infusion of distilled water after arginine vasopressin injection.
Results: The serum and brain concentrations of CEZ at the onset of seizures increased with increasing infusion rate, but the CSF concentration of CEZ at the onset of seizures was not affected by the infusion rate. The concentration of CEZ in CSF at the onset of seizures was significantly lower in UL rats than control rats, whereas there was no difference between UN rats and their controls. Serum concentrations of Na+ and serum tonicity were lower in UL rats than UN rats. Hypotonic hyponatremia had no apparent effect on the CSF concentration of CEZ. The CSF concentration of CEZ at the onset of seizures was significantly lower in UN rats with hypotonic hyponatremia than their controls.
Conclusion: Renal failure with severe hypotonic hyponatremia is associated with increased central nervous system sensitivity to CEZ-induced seizures.