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Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity

Wenrui Sun1, Binchuan Hu2, Xiaoshan Zhang1,3

  • 1The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.

Drug Design, Development and Therapy
|February 24, 2021
PubMed
Abstract

Insights

Twice-daily dosing of polymyxin B in rats showed increased nephrotoxicity compared to once-daily administration. This suggests that administration frequency impacts polymyxin B

Area of Science:

  • Pharmacology
  • Nephrology
  • Toxicology

Background:

  • Polymyxin B is a critical antibiotic for treating multidrug-resistant Gram-negative infections.
  • Nephrotoxicity is a known adverse effect of Polymyxin B, but its relationship with dosing frequency is not well understood.

Purpose of the Study:

  • To investigate the impact of Polymyxin B administration frequency on nephrotoxicity.
  • To compare the renal effects of once-daily versus twice-daily dosing regimens.

Main Methods:

  • Sprague-Dawley rats were administered Polymyxin B subcutaneously for five days.
  • Three groups received different dosing frequencies: once daily (18 mg/kg/q24 h), twice daily (9 mg/kg/q12 h), or normal saline (control).
  • Renal function was assessed by measuring serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein excretion, with kidney pathology examined post-mortem.

Main Results:

  • Rats receiving twice-daily Polymyxin B exhibited higher levels of SCr, BUN, and urinary protein excretion compared to the once-daily group.
  • Pathological examination revealed more severe renal tubule damage, including cell exfoliation and necrosis, in the twice-daily group.
  • Both Polymyxin B groups showed significantly elevated markers of kidney injury compared to the control group.

Conclusions:

  • The frequency of Polymyxin B administration significantly influences its nephrotoxicity.
  • A twice-daily dosing regimen results in greater renal toxicity in rats than a once-daily regimen.
  • Optimizing Polymyxin B dosing frequency may be crucial for mitigating kidney damage in clinical practice.
Keywords:
dosefrequencynephrotoxicitypolymyxin Brenal

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