Konishi Hiroki, Morita Yukiko, Mizumura Miyo, Iga Ikumi, Nagai Katsuhito
Osaka Ohtani University, Tondabayashi, Japan.
J Chemother. 2013 Oct;25(5):273-8. doi: 10.1179/1973947812Y.0000000067.
We compared the degree of nephrotoxicity of vancomycin (VCM) administered once daily and twice daily in rats. VCM was intraperitoneally administered once daily to rats at a dose of 400 mg/kg (VCM-1-treated) or administered at a dose of 200 mg/kg twice daily at 12-hour intervals (VCM-2-treated) for 7 consecutive days. Creatinine clearance was decreased more markedly in VCM-1 rats relative to VCM-2 rats, although there was no significant difference in renal accumulation of VCM between the two groups. Renal superoxide dismutase activity was lower in VCM-1 rats than that in VCM-2 rats. The magnitude of histological change in kidney tissue was in agreement with the degree of alterations in the abovementioned biochemical values. These results suggest that the nephrotoxic effect of once-daily VCM administration is more pronounced than that of the twice-daily treatment. Our findings provide fundamental evidence for the advantage in choosing a divided VCM administration to attenuate nephrotoxicity.
我们比较了大鼠每日一次和每日两次给予万古霉素（VCM）的肾毒性程度。将VCM以400mg/kg的剂量每日一次腹腔注射给大鼠（VCM-1处理组），或以200mg/kg的剂量每隔12小时每日两次腹腔注射给大鼠（VCM-2处理组），连续7天。相对于VCM-2大鼠，VCM-1大鼠的肌酐清除率下降更为明显，尽管两组之间VCM在肾脏中的蓄积没有显著差异。VCM-1大鼠的肾脏超氧化物歧化酶活性低于VCM-2大鼠。肾组织的组织学变化程度与上述生化值的改变程度一致。这些结果表明，每日一次给予VCM的肾毒性作用比每日两次给药更为明显。我们的研究结果为选择分次给予VCM以减轻肾毒性的优势提供了基础证据。
