Background: Polymyxin B, as the final treatment against multidrug-resistant Gram-negative bacilli, is widely used in clinical practice. However, little is known about the nephrotoxicity of polymyxin B. The purpose of this study was to elucidate the relationship between polymyxin B nephrotoxicity and daily administration frequency.
Methods: Sprague–Dawley rats were randomly divided into three groups: 18 mg/kg/q24 h group (Group A, once daily), 9 mg/kg/q12 h group (Group B, twice daily), and normal saline control group (Group C). The rats were injected subcutaneously for 5 consecutive days with the same daily total dose and different frequency of administration. The serum creatinine (SCr) and blood urea nitrogen (BUN) of each group before administration (0 h), and 8 and 24 h after administration, were measured by tail vein blood sampling. On the sixth day, the rats in each group were killed, the left kidney was taken for pathological section observation, and the results of each group were compared.
Results: After 96 h of administrated polymyxin B, the total average level of SCr in Group A was 56.98± 12.42 μmol/L, that of Group B was 52.02± 8.68 μmol/L, and that of Group C was 34.36± 5.39 μmol/L. BUN was 9.86± 4.58, 10.54± 4.08, and 3.55± 0.73 mmol/L in Groups A, B, and C, respectively. The daily urinary protein excretion was 5004.45± 1333.84 μg in Group A, 4608.04± 1444.42 μg in Group B, and 2096.33± 215.28 μg in Group C. In addition, according to the observation of pathological slices, compared with Group A, the number of exfoliated and necrotic cells of renal tubules in Group B was higher, and the morphological changes were more serious.
Conclusion: The experimental results showed that the renal toxicity in rats treated with a twice-daily subcutaneous dose of polymyxin B was higher than that in rats treated with once-daily dose of polymyxin B.



中文翻译：

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多粘菌素B不同给药频率对大鼠肾毒性的影响

背景：多粘菌素 B 作为抗多重耐药革兰氏阴性杆菌的最终治疗方法，在临床实践中得到广泛应用。然而，人们对多粘菌素 B 的肾毒性知之甚少。本研究的目的是阐明多粘菌素 B 的肾毒性与每日给药频率之间的关系。
方法：Sprague-Dawley大鼠随机分为三组：18 mg/kg/q24 h组（A组，每日1次）、9 mg/kg/q12 h组（B组，每日2次）和生理盐水对照组（组C）。大鼠皮下注射连续5天，每日总剂量相同，给药频率不同。尾静脉采血测定各组给药前(0 h)及给药后8、24 h的血清肌酐(SCr)和血尿素氮(BUN)。第6天处死各组大鼠，取左肾作病理切片观察，比较各组结果。
结果：多粘菌素B给药96 h后，A组总平均SCr水平为56.98±12.42 μmol/L，B组为52.02±8.68 μmol/L，C组为34.36±5.39 μmol/L。A、B 和 C 组的 BUN 分别为 9.86±4.58、10.54±4.08 和 3.55±0.73 mmol/L。A组每日尿蛋白排泄量为5004.45±1333.84 μg，B组为4608.04±1444.42 μg，C组为2096.33±215.28 μg。 B组肾小管脱落坏死细胞较多，形态学改变较严重。
结论：实验结果表明，每天两次皮下注射多粘菌素B的大鼠肾毒性高于每天一次注射多粘菌素B的大鼠。