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Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity

Authors Sun W, Hu B, Zhang X, Wang Y, Xiang Z, Lin G

Received 17 October 2020

Accepted for publication 7 January 2021

Published 16 February 2021 Volume 2021:15 Pages 611—616

DOI https://doi.org/10.2147/DDDT.S287332

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Wenrui Sun,1,* Binchuan Hu,2,* Xiaoshan Zhang,1,3 Yuzhen Wang1 1,3 Zheng Xiang,3 Guanyang Lin1

1The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Yongjia People’s Hospital, Wenzhou, 325100, People’s Republic of China; 3Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Guanyang Lin
The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Wenzhou, 325000, People’s Republic of China
Tel/Fax +86 105 557 9706
Email 13867702133@163.com

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.

Keywords: polymyxin B, dose, frequency, renal, nephrotoxicity

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