title: Comparative toxicity of oral cephalosporin antibiotics in the rabbit and in a rabbit kidney cell line (LLC-RK(1)).
abstract: The nephrotoxic potential of four oral cephalosporin antibiotics, cephalexin, cefaclor, LY195885 and LY171217, was determined in rabbits given single oral doses of 250-500 mg/kg body weight. Histopathological changes, blood chemistry, and ex vivo renal slice function were evaluated 48 hr after dosing. Additionally, the viability of rabbit renal cells in culture (LLC-RK(1)) was evaluated by nigrosin dye exclusion after 48 hr exposure to each antibiotic at concentrations of 0.5-2.0 mg/ml. Only LY171217 was significantly nephrotoxic in vivo. Prominent lesions were observed at 500 mg/kg body weight and were accompanied by marked increases in blood urea nitrogen and serum creatinine, and decreases in ex vivo renal slice gluconeogenesis and p-aminohippurate and tetraethylammonium uptake. In vitro toxicity to renal cells correlated well with the in vivo results yielding TC(50) values (TC(50) = concentration producing 50% lethality) > 1.0 mg/ml for cephalexin, LY195885 and cefaclor. LY171217, on the other hand, was significantly toxic in vitro (TC(50) = < 0.5). These results suggest that renal cells in culture may provide a useful method for examining the nephrotoxic potential of oral cephalosporins before in vivo studies.
authors.affiliation: Toxicology Division, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Williams
authors.forename: M K
authors.initials: MK
authors.lastname: Buening
authors.forename: C L
authors.initials: CL
authors.lastname: Gries
authors.forename: G K
authors.initials: GK
authors.lastname: Hanasono
authors.forename: D A
authors.initials: DA
authors.lastname: Laska
authors.forename: R N
authors.initials: RN
authors.lastname: Tamura
authors.forename: R A
authors.initials: RA
authors.lastname: Heim