Bennett W M, Plamp C E, Gilbert D N, Parker R A, Porter G A
J Infect Dis. 1979 Oct;140(4):576-80. doi: 10.1093/infdis/140.4.576.
Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10-day treatment period. The TID rats had the lowest peak serum levels, but, after 10 days of drug administration, the serum creatinine concentration (2.8 +/- 0.2 mg/100 ml, mean +/- SE) was significantly higher than in control rats (0.6 +/- 0.01 mg/100 ml) (P less than 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 +/- 77 micrograms/g in the QD rats and 820 +/- 29 micrograms/g in the TID rats (P less than 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. The results suggest that dose frequency should be considered when data from different laboratories are compared.
通过每天以40mg/kg的标准肾毒性剂量，分一次（每日一次）、两次或三次（每日三次）给大鼠注射庆大霉素，来改变其血清中庆大霉素的峰值水平。每日一次给药的大鼠血清峰值水平最高，但在10天的治疗期内血清肌酐浓度没有明显升高。每日三次给药的大鼠血清峰值水平最低，但是在给药10天后，其血清肌酐浓度（2.8±0.2mg/100ml，均值±标准误）显著高于对照大鼠（0.6±0.01mg/100ml）（P<0.001）。庆大霉素治疗两天后，每日一次给药的大鼠肾脏中庆大霉素浓度为269±77μg/g，每日三次给药的大鼠为820±29μg/g（P<0.001）。在这个大鼠模型中，给药频率比庆大霉素的血清峰值浓度在肾毒性发展过程中是更重要的因素。结果表明，在比较不同实验室的数据时应考虑给药频率。
