Product Monograph PrCEFTIN® PrCEFTIN® - GlaxoSmithKline

Rat: Repeated dose study
Rats received cefuroxime at doses ranging from 1 to 5 g/kg/day subcutaneously for 10
days. There was no histological evidence of tubular necrosis at 5 g/kg, but transient
increases in urine volume, protein and enzymes, which peaked at day 2-3 were
observed. The body weights of the animals were significantly reduced for the high dose
group.
Combination with aminoglycosides
Rats were treated with gentamicin (35 mg/kg) for 10 days. Cefuroxime sodium was
given either concomitantly during the 10 days or as a single dose with the ninth dose of
gentamicin. Gentamicin-induced tubular necrosis was not potentiated by the
administration of single doses of cefuroxime up to 6 g/kg/day. Multiple doses of
cefuroxime up to 4 g/kg protected rats against gentamicin-induced nephrotoxicity, but at
doses of 6 g/kg/day of cefuroxime, severe tubular necrosis was observed after 4 days of
treatment. Similar results were found with amikacin and tobramycin.
Mutagenicity Studies
Several standard assays were done to assess the mutagenic properties of cefuroxime
axetil. These included both in vitro (Ames test, fluctuation test, gene conversion assay)
and in vivo (micronucleus tests) assays.
November 30, 2010
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