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Aminoglycoside nephrotoxicity: do time and frequency of administration matter?
1Centre de Recherche en Infectiologie, and Université Laval, Ste-Foy, Quebec, Canada. denis.beauchamp@crchul.ulaval.ca
Abstract:
Aminoglycosides remains the mainstay in the treatment of gram-negative infections despite their potential oto-and nephrotoxicity although alternatives with equal or better efficacy are available. Several approaches were investigated to decrease aminoglycosides nephrotoxicity. Among them, only the once-daily dosing of aminoglycosides has been brought to the clinic and physicians are now increasingly adopting this approach to reduce the toxicity of these agents. The incidence of aminoglycoside nephrotoxicity can be further reduced in view of the recent data on the circadian variations of their nephrotoxicity. In fact, it has been clearly demonstrated in both experimental animals and humans that the toxicity is maximal when the drug is injected during the rest period compared with the activity period. Thus, injecting aminoglycosides once-daily at the time of the lowest toxicity is actually the most interesting and clinically applicable approach to reduce aminoglycosides toxicity.
Insights
Aminoglycosides treat gram-negative infections but can be toxic. Once-daily dosing reduces toxicity, and timing injections during low-toxicity periods further minimizes harm.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Aminoglycosides are crucial for treating gram-negative infections.
- Nephrotoxicity and ototoxicity are significant side effects of aminoglycosides.
- Alternative treatments exist but aminoglycosides remain a mainstay.
Purpose of the Study:
- To investigate methods for reducing aminoglycoside-induced nephrotoxicity.
- To evaluate the clinical applicability of timing aminoglycoside administration based on circadian rhythms.
- To optimize aminoglycoside dosing strategies for improved patient safety.
Main Methods:
- Review of existing data on aminoglycoside nephrotoxicity.
- Analysis of experimental and human studies on circadian variations in drug toxicity.
- Evaluation of once-daily dosing strategies in clinical practice.
Main Results:
- Once-daily aminoglycoside dosing is a clinically adopted strategy to reduce toxicity.
- Aminoglycoside nephrotoxicity exhibits significant circadian variation.
- Toxicity is highest when administered during the organism's rest period and lowest during the activity period.
Conclusions:
- Administering aminoglycosides once-daily during the period of lowest toxicity is a promising clinical approach.
- This strategy can further reduce aminoglycoside-induced nephrotoxicity beyond standard once-daily dosing.
- Optimizing administration time offers a practical method to enhance the safety profile of aminoglycosides.